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1
Gregory, Mary Sarah-Jane, and n/a. "Thioredoxin and Oxidative Stress." Griffith University. School of Health Science, 2004. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20040301.082639.
Повний текст джерелаАнотація:
The experiments described in this thesis involve the expression and characterisation of recombinant truncated thioredoxin (tTrx) and the potential involvement that thioredoxin (Trx) has in the cellular responses to oxidative stress. Truncated Trx (80 amino acids) was expressed from a plasmid containing the ORF for tTrx that had been introduced into E.coli BL-21(DE3) cells. The protein was initially extracted using a combination of high concentrations of urea, high pH levels, and multiple sonification steps to remove the tTrx from inclusion bodies formed during expression. This procedure produced a stable solution of tTrx. Purification of tTrx from this protein solution required anion exchange chromatography followed by gel permeation in a HPLC system to obtain fully purified, recombinant tTrx which allowed further characterisation studies to be undertaken. An initial investigation into tTrx was performed to determine some basic physical, biochemical and functional aspects of this hitherto relatively undefined protein. Analysis by sedimentation equilibrium indicated that freshly prepared tTrx forms a single species with a molecular weight of 18.8kDa. This value indicates that recombinant tTrx naturally forms a dimer in solution that was shown to be non-covalent in nature and stable in solution. The capacity of tTrx to reduce protein disulphide bonds was determined using the insulin reduction assay. Results show that tTrx lacks this particular redox ability. The rate of oxidisation at 4 degrees C was analysed using free thiol determination, sedimentation equilibrium and SDS-PAGE patterning. Results indicated a steady rise in the degree of oxidation of tTrx over an eight day period. After six days the oxidated protein consistently displayed the presence of intramolecular disulphide bonds. Covalently-linked disulphide dimers and higher molecular weight oligomers were detectable after eight days oxidation. An investigation of the reducing capacity of the basic Trx system determined that fully oxidised tTrx was unable to act alone as a substrate for thioredoxin reductase (TR). However, when reduced Trx was added to the system, it appeared capable of acting as an electron donor to the oxidised tTrx in order to reduce disulphide groups. Recombinant tTrx was successfully radiolabelled with Trans 35S-methionine/cysteine for use in cell association studies. No evidence was found to indicate the presence of a receptor for tTrx on either MCF-7 or U-937 cells. Findings suggest that a low level of non-specific binding of tTrx to these cell lines rather than a classical ligand-binding mechanism occurs thus suggesting the absence of a cell surface receptor for tTrx. The role that Trx may play in the cellular responses to oxidative stress was also investigated. The chemical oxidants hydrogen peroxide (H2O2) and diamide were used to establish an in vitro model of oxidative stress for the choriocarcinoma cytotrophoblast cell line JEG-3. Cellular function was assessed in terms of membrane integrity, metabolic activity and the ability to synthesis new DNA following exposure to these oxidants. Results indicated that both agents were capable of causing cells to undergo oxidative stress without inducing immediate apoptosis or necrosis. Initially, JEG-3 cells exposed to 38μM or 75μM H2O2 or 100μM diamide were shown to display altered cell metabolism and DNA synthesis without loss to cell viability or membrane integrity. Cells were also shown to be capable of some short-term recovery but later lapsed into a more stressed state. Expression levels of Trx were studied to determine whether this type of chemical stress caused a change in intercellular protein levels. Both cELISA and western blotting results indicated that only cells exposed to 100μM diamide displayed any significant increase in Trx protein levels after 6 or 8hrs exposure to the oxidant. Further studies over a longer time-frame were also performed. These found that when JEG-3 cells were exposed to 18μM H2O2 or 200μM diamide over 12-48hrs, a positive correlation between increasing endogenous Trx protein levels and a decline in cell proliferation was observed. Cytotrophoblast cells, which are responsible for implantation and placentation, are susceptible to oxidative stress in vivo and their anti-oxidant capacity is fundamental to the establishment of pregnancy. The findings obtained during these studies suggest that Trx plays a role in this process.
2
Gregory, Mary Sarah-Jane. "Thioredoxin and Oxidative Stress." Thesis, Griffith University, 2004. http://hdl.handle.net/10072/367183.
Повний текст джерелаАнотація:
The experiments described in this thesis involve the expression and characterisation of recombinant truncated thioredoxin (tTrx) and the potential involvement that thioredoxin (Trx) has in the cellular responses to oxidative stress.
Truncated Trx (80 amino acids) was expressed from a plasmid containing the ORF for tTrx that had been introduced into E.coli BL-21(DE3) cells. The protein was initially extracted using a combination of high concentrations of urea, high pH levels, and multiple sonification steps to remove the tTrx from inclusion bodies formed during expression. This procedure produced a stable solution of tTrx. Purification of tTrx from this protein solution required anion exchange chromatography followed by gel permeation in a HPLC system to obtain fully purified, recombinant tTrx which allowed further characterisation studies to be undertaken.
An initial investigation into tTrx was performed to determine some basic physical, biochemical and functional aspects of this hitherto relatively undefined protein. Analysis by sedimentation equilibrium indicated that freshly prepared tTrx forms a single species with a molecular weight of 18.8kDa. This value indicates that recombinant tTrx naturally forms a dimer in solution that was shown to be non-covalent in nature and stable in solution. The capacity of tTrx to reduce protein disulphide bonds was determined using the insulin reduction assay. Results show that tTrx lacks this particular redox ability.
The rate of oxidisation at 4 degrees C was analysed using free thiol determination, sedimentation equilibrium and SDS-PAGE patterning. Results indicated a steady rise in the degree of oxidation of tTrx over an eight day period. After six days the oxidated protein consistently displayed the presence of intramolecular disulphide bonds. Covalently-linked disulphide dimers and higher molecular weight oligomers were detectable after eight days oxidation.
An investigation of the reducing capacity of the basic Trx system determined that fully oxidised tTrx was unable to act alone as a substrate for thioredoxin reductase (TR). However, when reduced Trx was added to the system, it appeared capable of acting as an electron donor to the oxidised tTrx in order to reduce disulphide groups.
Recombinant tTrx was successfully radiolabelled with Trans 35S-methionine/cysteine for use in cell association studies. No evidence was found to indicate the presence of a receptor for tTrx on either MCF-7 or U-937 cells. Findings suggest that a low level of non-specific binding of tTrx to these cell lines rather than a classical ligand-binding mechanism occurs thus suggesting the absence of a cell surface receptor for tTrx.
The role that Trx may play in the cellular responses to oxidative stress was also investigated. The chemical oxidants hydrogen peroxide (H2O2) and diamide were used to establish an in vitro model of oxidative stress for the choriocarcinoma cytotrophoblast cell line JEG-3. Cellular function was assessed in terms of membrane integrity, metabolic activity and the ability to synthesis new DNA following exposure to these oxidants. Results indicated that both agents were capable of causing cells to undergo oxidative stress without inducing immediate apoptosis or necrosis. Initially, JEG-3 cells exposed to 38μM or 75μM H2O2 or 100μM diamide were shown to display altered cell metabolism and DNA synthesis without loss to cell viability or membrane integrity. Cells were also shown to be capable of some short-term recovery but later lapsed into a more stressed state.
Expression levels of Trx were studied to determine whether this type of chemical stress caused a change in intercellular protein levels. Both cELISA and western blotting results indicated that only cells exposed to 100μM diamide displayed any significant increase in Trx protein levels after 6 or 8hrs exposure to the oxidant. Further studies over a longer time-frame were also performed. These found that when JEG-3 cells were exposed to 18μM H2O2 or 200μM diamide over 12-48hrs, a positive correlation between increasing endogenous Trx protein levels and a decline in cell proliferation was observed. Cytotrophoblast cells, which are responsible for implantation and placentation, are susceptible to oxidative stress in vivo and their anti-oxidant capacity is fundamental to the establishment of pregnancy. The findings obtained during these studies suggest that Trx plays a role in this process.<br>Thesis (Masters)<br>Master of Philosophy (MPhil)<br>School of Health Sciences<br>Full Text
3
Nälsén, Cecilia. "Measurement and evaluation of antioxidant status and relation to oxidative stress in humans /." Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6742.
Повний текст джерела
4
Byon, Chang Hyun. "Oxidative stress-stimulated vascular calcification." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2009. https://www.mhsl.uab.edu/dt/2010r/byon.pdf.
Повний текст джерела
5
Vanderlelie, Jessica, and n/a. "Placental Oxidative Stress in Preeclampsia." Griffith University. School of Medical Science, 2006. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20060918.161726.
Повний текст джерелаАнотація:
Affecting 6-8% of all pregnancies, preeclampsia is the leading cause of maternal morbidity in the western world and is charactensed by hypertension, proteinuria, edema and platelet aggregation. Despite its prevalence and severity, no comprehensive theory or single factor has been suggested to explain the pathophysiology of this multi system disorder of pregnancy, with the only therapies being bed rest, pharmacological symptom management and if necessary early delivery. Oxidative stress plays an important role in the pathophysiology of preeclampsia, resulting from defective trophoblast invasion, reductions in placental perfusion and placental hypoxia/reoxygenation. The inability of endogenous antioxidant systems up regulated in normal pregnancy, to control increased levels of oxidative stress, is suggested as a possible factor in the feed forward generation of reactive oxygen species and placental oxidative stress. That in turn may stimulate increased syncytiotrophoblast apoptosis, endothelial cell activation and the maternal hyper immune response characteristic of preeclampsia. Analysis of the research literature revealed that previous evaluations of placental oxidation and antioxidant enzyme activity in preeclampsia were by no means comprehensive, and exhibited significant inter-study variations. It was the aim of this thesis to clarify the placental oxidative state and the endogenous antioxidant activity of glutathione peroxidase, thioredoxin reductase, thioredoxin and superoxide dismutase in human placentae in an attempt to determine if variations in antioxidant function were due to changes in gene expression or protein oxidation. The findings reported in this thesis indicate the presence of increased levels of oxidative stress in the preeclamptic placenta, associated with significant reductions in antioxidant enzyme capacity. Quantitative real-time PCR analysis of placental samples revealed that deceases in antioxidant capacity in the placenta are more likely to be related to the significant oxidative burden within the tissue rather than reductions in gene expression. A number of animal models exist to investigate components of preeclampsia pathophysiology, however the ability of these models to mimic the oxidative and antioxidant features of preeclampsia remains unclear. The exposure of pregnant rats to N(G)-nitro-L-arginine methyl ester is a widely used model of endothelial cell dysfunction during preeclampsia. It was the aim of this thesis to determine the biochemical characteristics of this model in an attempt to assess its effectiveness in mimicking oxidative changes in the preeclamptic placenta. Although this model is capable of producing a syndiome in rats similar to the disorder in terms of physiology, this is not manifest in terms of placental biochemistry. The importance of selenium in the synthesis of selenobased antioxidants such as glutathione peroxidase and thioredoxin reductase is well documented. Increasing demand for selenium by the developing fetus may be linked to reductions in selenium status during pregnancy. Considering preeclampsia is associated with significant reductions in selenium status it may be hypothesised that reductions in antioxidant function may be linked to selenium inadequacy. The modulation of dietary selenium in pregnant rats was used to determine the importance of selenium during pregnancy and its effect on antioxidant function and placental oxidative stress. The results of this analysis revealed that selenium deficiency causes a pregnancy specific condition similar to preeclampsia. This condition was found to be associated with increased placental oxidative stress and significant reductions in the systemic activity of selenobased antioxidants that could be modified through selenium supplementation. In summary, data obtained in this thesis indicate that placental oxidative stress and reduced antioxidant enzyme activity play a significant role in the pathogenesis of preeclampsia. These studies support the hypothesis that antioxidant sufficiency is crucial in the maintenance of oxidative balance and that antioxidant dysfunction may result in damage to the placenta and the progression of the disease. These novel data further our understanding of the pathophysiology of preeclampsia and provide new insight into the pathogenesis of clinical complications exhibited in this condition, suggesting antioxidant therapy as a possible means for improving the health outcomes of both mother and baby.
6
Afzal, Maryam. "Breast cancer and oxidative stress." Thesis, Cardiff University, 2009. http://orca.cf.ac.uk/55856/.
Повний текст джерелаАнотація:
Endocrine and anti-EGFR strategies are used to treat breast cancer. Unfortunately, resistance can be acquired. Deciphering resistance mechanisms remains essential to design treatments for this adverse state. Oxidative stress is the cellular imbalance of pro-oxidants (promoting cell death) and antioxidants (facilitating cell survival and chemotherapy/radiotherapy resistance). However, it remains unexplored whether endocrine or anti-EGFR resistance also associates with altered redox balance. In this project, redox balance was examined using in vitro human resistant breast cancer models TAMR, FASR, X-MCF and NEW DUBS, comparing with responsive w/tMCF7 cells using microarray analysis, PCR, and TAC, ROS, or MTT assays. Pro-oxidant levels increased significantly in all resistant models but this did not impact adversely on growth. Significantly increased antioxidant levels were also observed in all resistant models, perhaps limiting pro-oxidant increases to maintain cell survival. Antioxidants were also significantly induced by antihormones in w/tMCF7 cells that may limit apoptosis with early treatment. Expression of 15 antioxidant genes increased in resistant cells spanning multiple resistant states. While gefitinib challenge revealed many antioxidant genes were EGFR/kinase signalling-regulated in TAMR cells, gefitinib and further signal transduction inhibitors (STIs) indicated total antioxidant capacity was not. Thus, additional genes/signalling probably drive increased antioxidants in resistant cells future deciphering and depletion of antioxidants could feasibly block cell survival in multiple resistant states. Several STIs further increased pro-oxidants in TAMR cells, indicating oxidative stress was also not EGFR/kinase-promoted since STIs also further increased antioxidant capacity, this may again limit pro-oxidant increases and hence apoptotic effect. Importantly, the thesis revealed resistant cells may be particularly sensitive to agents inducing excessive oxidative stress. Redox balance and feasibility of agents influencing redox remains complex. However, new findings and concepts emerging from this thesis are worthy of future exploration for potential treatments for resistance to endocrine/anti-EGFR agents.
7
Wood, Christopher. "Oxidative stress and seed survival." Thesis, Abertay University, 1998. https://rke.abertay.ac.uk/en/studentTheses/79d28b74-9210-4ebd-a3b8-66a610bd8c87.
Повний текст джерелаАнотація:
Free radical and aldehydic breakdown product content were determined, by EPR and UV / visible spectroscopy, primarily in intermediate (desiccation tolerant) seeds of <i>Carica papaya</i> L. (Papaya) and recalcitrant (desiccation intolerant) seeds of <i>Aesculus hippocastanum</i> L. (Horse chestnut), but also in other species covering a range of desiccation tolerances, with a view to determining the role of oxidative stress as a diagnostic marker for desiccation tolerance. Axes of non-senescent highly viable recalcitrant seeds of horse chestnut were metabolically active, contained products of lipid peroxidation, displayed low levels of enzymatic protection against activated oxygen and peroxides, and a two-peak free radical EPR signal. During fully hydrated storage at 16 °C for up to 18 months, seeds exhibited, sequentially, an increase in germination rate, a transient increase in intensities of both the low field and high field EPR peaks, a significant increase in membrane leakage and decrease in seed viability, germination rate, and SOD and peroxidase activities. Drying 'unstored' seeds below and embryonic axis moisture content of 40 to 50 % initiated viability loss. At < 25 % moisture content all axes were inviable and displayed a 2- to 4-fold increase in solute leakage, lipid peroxidation products and the low field EPR signal. Seed desiccation sensitivity increased with hydrated storage. The accumulation of lipid peroxidation products and free radicals on drying generally occurred to a greater extent, or at a higher moisture content, than observed with unstored seeds. The results indicate a mediating role for oxidative stress in recalcitrant seed viability loss which is differentially expressed during hydrated, 'natural' ageing and desiccation. Similar trends were seen in other recalcitrant species with the increase in lipid peroxidation products occurring around the point of viability loss. However the study of a more orthodox species (papaya) revealed no such trends.
8
Bennett, Stuart James. "Oxidative stress biomarkers in dementia." Thesis, University of Birmingham, 2011. http://etheses.bham.ac.uk//id/eprint/1449/.
Повний текст джерелаАнотація:
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder which is thought to affect 26.6 million individuals worldwide. There is growing concern over a worldwide dementia epidemic that is predicted to develop over the coming decades. The evidence thus far suggests that increased levels of oxidative stress and vascular risk factors are two major contributors, amongst others, to AD development. The thesis aimed to investigate markers of oxidative stress in AD plasma. Moreover, the oxidative status of specific proteins was investigated using both hypothesis driven and proteomic approaches. Results presented in this thesis suggest that global plasma protein oxidation levels are not different when AD and control subjects are compared, but that individual plasma proteins are specific targets for oxidative modification in AD. The thesis explores different methodologies to assess oxidative changes in AD. In addition it demonstrates that emerging novel and powerful mass spectrometry techniques can be employed successfully to identify several proteins modified by oxidation, providing an initial starting point for further investigation.
9
Vanderlelie, Jessica. "Placental Oxidative Stress in Preeclampsia." Thesis, Griffith University, 2006. http://hdl.handle.net/10072/365679.
Повний текст джерелаАнотація:
Affecting 6-8% of all pregnancies, preeclampsia is the leading cause of maternal morbidity in the western world and is charactensed by hypertension, proteinuria, edema and platelet aggregation. Despite its prevalence and severity, no comprehensive theory or single factor has been suggested to explain the pathophysiology of this multi system disorder of pregnancy, with the only therapies being bed rest, pharmacological symptom management and if necessary early delivery. Oxidative stress plays an important role in the pathophysiology of preeclampsia, resulting from defective trophoblast invasion, reductions in placental perfusion and placental hypoxia/reoxygenation. The inability of endogenous antioxidant systems up regulated in normal pregnancy, to control increased levels of oxidative stress, is suggested as a possible factor in the feed forward generation of reactive oxygen species and placental oxidative stress. That in turn may stimulate increased syncytiotrophoblast apoptosis, endothelial cell activation and the maternal hyper immune response characteristic of preeclampsia. Analysis of the research literature revealed that previous evaluations of placental oxidation and antioxidant enzyme activity in preeclampsia were by no means comprehensive, and exhibited significant inter-study variations. It was the aim of this thesis to clarify the placental oxidative state and the endogenous antioxidant activity of glutathione peroxidase, thioredoxin reductase, thioredoxin and superoxide dismutase in human placentae in an attempt to determine if variations in antioxidant function were due to changes in gene expression or protein oxidation. The findings reported in this thesis indicate the presence of increased levels of oxidative stress in the preeclamptic placenta, associated with significant reductions in antioxidant enzyme capacity. Quantitative real-time PCR analysis of placental samples revealed that deceases in antioxidant capacity in the placenta are more likely to be related to the significant oxidative burden within the tissue rather than reductions in gene expression. A number of animal models exist to investigate components of preeclampsia pathophysiology, however the ability of these models to mimic the oxidative and antioxidant features of preeclampsia remains unclear. The exposure of pregnant rats to N(G)-nitro-L-arginine methyl ester is a widely used model of endothelial cell dysfunction during preeclampsia. It was the aim of this thesis to determine the biochemical characteristics of this model in an attempt to assess its effectiveness in mimicking oxidative changes in the preeclamptic placenta. Although this model is capable of producing a syndiome in rats similar to the disorder in terms of physiology, this is not manifest in terms of placental biochemistry. The importance of selenium in the synthesis of selenobased antioxidants such as glutathione peroxidase and thioredoxin reductase is well documented. Increasing demand for selenium by the developing fetus may be linked to reductions in selenium status during pregnancy. Considering preeclampsia is associated with significant reductions in selenium status it may be hypothesised that reductions in antioxidant function may be linked to selenium inadequacy. The modulation of dietaty selenium in pregnant rats was used to determine the importance of selenium during pregnancy and its effect on antioxidant function and placental oxidative stress. The results of this analysis revealed that selenium deficiency causes a pregnancy specific condition similar to preeclampsia. This condition was found to be associated with increased placental oxidative stress and significant reductions in the systemic activity of selenobased antioxidants that could be modified through selenium supplementation. In summary, data obtained in this thesis indicate that placental oxidative stress and reduced antioxidant enzyme activity play a significant role in the pathogenesis of preeclampsia. These studies support the hypothesis that antioxidant sufficiency is crucial in the maintenance of oxidative balance and that antioxidant dysfunction may result in damage to the placenta and the progression of the disease. These novel data further our understanding of the pathophysiology of preeclampsia and provide new insight into the pathogenesis of clinical complications exhibited in this condition, suggesting antioxidant therapy as a possible means for improving the health outcomes of both mother and baby.<br>Thesis (PhD Doctorate)<br>Doctor of Philosophy (PhD)<br>School of Medical Science<br>Full Text
10
Bolotta, Alessandra <1982>. "Oxidative Stress and Friedreich’s Ataxia." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6282/1/Bolotta_Alessandra_tesi.pdf.
Повний текст джерелаАнотація:
Friedreich’s Ataxia (FRDA) is a neurodegenerative disorder caused by a deficiency of the protein frataxin and characterized by oxidative stress. The first aim of my research project was to analyze the effects of tocotrienol in FRDA patients. Patients received for 2 months a low dose of tocotrienol. A number of biochemical parameters related to oxidative stress were studied. We consistently showed that taking for 2 months a low dose of tocotrienol led to the decrease of oxidative stress indexes in FRDA patients. Also, this study provides a suitable model to investigate the efficacy of natural compounds to counteract the oxidative stress in FRDA.
Furthermore, we investigated whether the tocotrienol was able to modulate the expression of the frataxin isoforms (FXN-1, FXN -2, FXN-3) in FRDA patients. We demonstrated that tocotrienol leads to a specific and significant increase of FXN-3 expression. As no structural and functional details were available for FNX-2 and FXN-3, 3D-models were built. FXN-1, the canonical isoform, was then docked on the human iron-sulphur complex and functional interactions were computed; when FXN-1 was replaced by FXN-2 or FNX-3, we found that the interactions were maintained, thus suggesting a possible biological role for both isoforms.
The second aim of my research project was to investigate the role of a single nucleotide polymorphism (SNP) in the protein Sirtuin 6 in FRDA patients. In fact, it was known that those who harbour a SNP (Asn46/Ser46) in the gene enconding Sirt6 show a better outcome those individuals who are homozygous for the Asn 46 allele. We found that fibroblasts and iPSC-derived neurons from FRDA patients harboring the SNP (Asn46/Ser46) have a reduced amount of Sirt6 protein compared to cells from individuals who are homozygous for the prevalent Asn allele. Our studies provide new information on the role of Sirtuins in FRDA pathogenesis.
11
Bolotta, Alessandra <1982>. "Oxidative Stress and Friedreich’s Ataxia." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6282/.
Повний текст джерелаАнотація:
Friedreich’s Ataxia (FRDA) is a neurodegenerative disorder caused by a deficiency of the protein frataxin and characterized by oxidative stress. The first aim of my research project was to analyze the effects of tocotrienol in FRDA patients. Patients received for 2 months a low dose of tocotrienol. A number of biochemical parameters related to oxidative stress were studied. We consistently showed that taking for 2 months a low dose of tocotrienol led to the decrease of oxidative stress indexes in FRDA patients. Also, this study provides a suitable model to investigate the efficacy of natural compounds to counteract the oxidative stress in FRDA.
Furthermore, we investigated whether the tocotrienol was able to modulate the expression of the frataxin isoforms (FXN-1, FXN -2, FXN-3) in FRDA patients. We demonstrated that tocotrienol leads to a specific and significant increase of FXN-3 expression. As no structural and functional details were available for FNX-2 and FXN-3, 3D-models were built. FXN-1, the canonical isoform, was then docked on the human iron-sulphur complex and functional interactions were computed; when FXN-1 was replaced by FXN-2 or FNX-3, we found that the interactions were maintained, thus suggesting a possible biological role for both isoforms.
The second aim of my research project was to investigate the role of a single nucleotide polymorphism (SNP) in the protein Sirtuin 6 in FRDA patients. In fact, it was known that those who harbour a SNP (Asn46/Ser46) in the gene enconding Sirt6 show a better outcome those individuals who are homozygous for the Asn 46 allele. We found that fibroblasts and iPSC-derived neurons from FRDA patients harboring the SNP (Asn46/Ser46) have a reduced amount of Sirt6 protein compared to cells from individuals who are homozygous for the prevalent Asn allele. Our studies provide new information on the role of Sirtuins in FRDA pathogenesis.
12
Collins, Tracey Helen. "Investigation into the Effects of Oxidative Stress on Reproductive Development." The University of Waikato, 2007. http://hdl.handle.net/10289/2364.
Повний текст джерелаАнотація:
Nuclear transfer (NT), or cloning, which is the transfer of a donor nucleus to a recipient enucleated oocyte, has been successfully achieved to produce viable offspring in many species. The process is very inefficient, as reprogramming of the donor nucleus is required, and losses are high throughout development. Placentation abnormalities are a common feature amongst cloned animals. Incomplete nuclear reprogramming and erroneous epigenetic imprinting may contribute to aberrant protein transcription and DNA mutations, affecting mitochondrial metabolism and inducing cellular stress. In vitro produced embryos under high oxygen culture conditions may also suffer oxidative stress, with the resulting reactive oxygen species causing mitochondrial DNA mutations and cellular stress similar to clones. In this study, expression of oxidative stress protein markers (Hsp60, SOD2, Hsp70) in NT cotyledons were compared to artificial insemination (AI) at different time points of gestation (days 50, 100, and 150). As a continuum of the oxidative stress investigation in cloned cotyledons, in vitro produced embryos were cultured under 20% oxygen compared to the control 7% oxygen laboratory standard culture, with oxidative stress protein markers examined between the groups at blastocyst stage (day 7) and day 15. Embryo morphology was also observed to determine apparent physiological differences between the treatment and control embryos. No previous studies to date have investigated the developmental effects of oxidative stress in day 15 bovine embryos. The significant differences in oxidative stress proteins observed at several time points in the NT and AI groups were not repeatable, possibly due to sample freeze/thaw degradation. Morphological differences observed between embryos cultured in 20% oxygen and control groups were visually apparent, although not quantified. At day 15 manganese superoxide dismutase expression was significantly lower in the 20% group compared to control. The 20% oxygen group did not show higher heat shock protein 60 expression than control, however the same results have been observed in another study at blastocyst stage. The results of this study suggest that the effect of oxidative stress on embryonic development is evident yet inconclusive in bovine NT cotyledons, however does not appear apparent in day 15 embryos following culture in 20% oxygen.
13
Rajaraman, Gnana Oli [Verfasser], and Helga [Akademischer Betreuer] Stopper. "Oxidative stress : role in genomic damage and disease = Oxidativer Stress / Gnana Oli Rajaraman. Betreuer: Helga Stopper." Würzburg : Universitätsbibliothek der Universität Würzburg, 2012. http://d-nb.info/1024851885/34.
Повний текст джерела
14
Silva, Andreza Amaral da [UNESP]. "Estudo clínico, hemagasométrico e do estresse oxidativo em ovinos clinicamente sadios portadores de pneumonia." Universidade Estadual Paulista (UNESP), 2012. http://hdl.handle.net/11449/101285.
Повний текст джерелаАнотація:
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silva_aa_dr_botfmvz.pdf: 1478521 bytes, checksum: 3590a41144246c2ed3a4619905b51919 (MD5)<br>Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)<br>Nas espécies domésticas as pneumonias cursam com intensa resposta inflamatória e acúmulo de células fagocíticas nos pulmões, levando a danos expressivos das estruturas do trato respiratório e à função pulmonar devido ao estresse oxidativo decorrente da liberação de grandes quantidades de Espécies Reativas do Oxigênio (ERO) durante a explosão respiratória. O objetivo deste estudo foi analisar o status oxidativo, a resposta inflamatória e a gasometria arterial, de ovinos sadios (n=20) e com diagnóstico clínico de pneumonia (n=20). Inicialmente os animais foram submetidos ao exame clínico e divididos em dois grupos: I) G1/controle, composto pelos animais clinicamente sadios e II) G2, composto pelos animais portadores de pneumonia. O status oxidativo foi avaliado por determinação indireta da atividade enzimática da Superóxido Dismutase (SOD) e Glutationa Peroxidase (GSH-Px) e das concentrações de Glutationa total (GSH-t) e Substâncias Reativas ao Ácido Tiobarbitúrico (TBARS) no sangue periférico por método colorimétrico. A resposta inflamatória foi avaliada pelo hemograma e proteína total e fibrinogênio plasmáticos e a função pulmonar pela determinação das variáveis hemogasométricas Pressão Arterial de Oxigênio (PaO2), Pressão Arterial de Gás Carbônico (PaCO2), Hidrogeniônico (pH), Saturação de Oxigênio (SO2), Bicarbonato (HCO3¯), Dióxido de Carbono Total (TCO2) e Excesso de Bases (EB), avaliados em sangue arterial. O leucograma revelou leucocitose com neutrofilia, eosinofilia, monocitose e linfopenia nos animais doentes (p<0,05). Com relação aos parâmetros bioquímicos, os ovinos portadores de pneumonia apresentaram aumento significativo (p>0,05) da concentração de fibrinogênio e proteína plasmática total. Os animais portadores de pneumonia apresentaram diminuição estatisticamente...<br>In domestic species, pneumonia is accompanied by intense inflammatory response and accumulation of phagocytic cells in the lungs, causing structural damage of the respiratory tract due to oxidative stress resulting from the release of large amounts of Reactive Oxygen Species (ROS) during the respiratory burst. The aim of this study was to analyze the oxidative status, inflammatory response and arterial blood gases values in healthy sheep (n=20) and animals with a clinically diagnosed pneumonia (n = 20). After physical examination the animals were divided into two groups: i) G1/control, composed of clinically healthy animals and ii) G2, composed of animals with pneumonia. The oxidative status was assessed by indirect determinations of enzymatic activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and concentrations of total glutathione (GSH-t) and thiobarbituric acid reactive substances (TBARS) in peripheral blood by a colorimetric method. The inflammatory response was evaluated by complete blood count and total protein and plasma fibrinogen. The lung function was evaluated by determinations of blood gas parameters in arterial blood: Oxygen Pressure (PaO2) Pressure of Carbon Dioxide (PaCO2), Pressure Hydrogen (pH), Oxygen Saturation (SO2), Bicarbonate (HCO3¯), Total Carbon Dioxide (TCO2) and Base Excess (EB). The leucogram results showed Leukocytosis with neutrophilia, eosinophilia, monocytosis and lymphopenia in sick animals (p<0,05). With regard to biochemical parameters, sheep with pneumonia showed a significant increase (p<0,05) of fibrinogen and total plasma protein concentrations. The animals from group G2 had a statistically significant reduction (p<0,05) in SOD and GSH-Px enzymatic activity and GSH-t concentration, while TBARS concentration was significantly higher (p<0,05). Arterial blood... (Complete abstract click electronic access below)
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Silva, Andreza Amaral da. "Estudo clínico, hemagasométrico e do estresse oxidativo em ovinos clinicamente sadios portadores de pneumonia /." Botucatu, 2012. http://hdl.handle.net/11449/101285.
Повний текст джерелаАнотація:
Orientador: Roberto Calderon Gonçalves<br>Banca: Simone Biagio Chiacchio<br>Banca: Raimundo de Souza Lopes<br>Banca: Fernando José Benesi<br>Banca: Débora Cristina Damasceno<br>Resumo: Nas espécies domésticas as pneumonias cursam com intensa resposta inflamatória e acúmulo de células fagocíticas nos pulmões, levando a danos expressivos das estruturas do trato respiratório e à função pulmonar devido ao estresse oxidativo decorrente da liberação de grandes quantidades de Espécies Reativas do Oxigênio (ERO) durante a explosão respiratória. O objetivo deste estudo foi analisar o status oxidativo, a resposta inflamatória e a gasometria arterial, de ovinos sadios (n=20) e com diagnóstico clínico de pneumonia (n=20). Inicialmente os animais foram submetidos ao exame clínico e divididos em dois grupos: I) G1/controle, composto pelos animais clinicamente sadios e II) G2, composto pelos animais portadores de pneumonia. O status oxidativo foi avaliado por determinação indireta da atividade enzimática da Superóxido Dismutase (SOD) e Glutationa Peroxidase (GSH-Px) e das concentrações de Glutationa total (GSH-t) e Substâncias Reativas ao Ácido Tiobarbitúrico (TBARS) no sangue periférico por método colorimétrico. A resposta inflamatória foi avaliada pelo hemograma e proteína total e fibrinogênio plasmáticos e a função pulmonar pela determinação das variáveis hemogasométricas Pressão Arterial de Oxigênio (PaO2), Pressão Arterial de Gás Carbônico (PaCO2), Hidrogeniônico (pH), Saturação de Oxigênio (SO2), Bicarbonato (HCO3¯), Dióxido de Carbono Total (TCO2) e Excesso de Bases (EB), avaliados em sangue arterial. O leucograma revelou leucocitose com neutrofilia, eosinofilia, monocitose e linfopenia nos animais doentes (p<0,05). Com relação aos parâmetros bioquímicos, os ovinos portadores de pneumonia apresentaram aumento significativo (p>0,05) da concentração de fibrinogênio e proteína plasmática total. Os animais portadores de pneumonia apresentaram diminuição estatisticamente... (Resumo completo, clicar acesso eletrônico abaixo)<br>Abstract: In domestic species, pneumonia is accompanied by intense inflammatory response and accumulation of phagocytic cells in the lungs, causing structural damage of the respiratory tract due to oxidative stress resulting from the release of large amounts of Reactive Oxygen Species (ROS) during the respiratory burst. The aim of this study was to analyze the oxidative status, inflammatory response and arterial blood gases values in healthy sheep (n=20) and animals with a clinically diagnosed pneumonia (n = 20). After physical examination the animals were divided into two groups: i) G1/control, composed of clinically healthy animals and ii) G2, composed of animals with pneumonia. The oxidative status was assessed by indirect determinations of enzymatic activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and concentrations of total glutathione (GSH-t) and thiobarbituric acid reactive substances (TBARS) in peripheral blood by a colorimetric method. The inflammatory response was evaluated by complete blood count and total protein and plasma fibrinogen. The lung function was evaluated by determinations of blood gas parameters in arterial blood: Oxygen Pressure (PaO2) Pressure of Carbon Dioxide (PaCO2), Pressure Hydrogen (pH), Oxygen Saturation (SO2), Bicarbonate (HCO3¯), Total Carbon Dioxide (TCO2) and Base Excess (EB). The leucogram results showed Leukocytosis with neutrophilia, eosinophilia, monocytosis and lymphopenia in sick animals (p<0,05). With regard to biochemical parameters, sheep with pneumonia showed a significant increase (p<0,05) of fibrinogen and total plasma protein concentrations. The animals from group G2 had a statistically significant reduction (p<0,05) in SOD and GSH-Px enzymatic activity and GSH-t concentration, while TBARS concentration was significantly higher (p<0,05). Arterial blood... (Complete abstract click electronic access below)<br>Doutor
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Ferreira, Paula Souza. "Atividade anti-inflamatória e antioxidante de flavonoides cítricos em camundongos submetidos a dieta indutora do estado pró-inflamatório /." Araraquara, 2014. http://hdl.handle.net/11449/113840.
Повний текст джерелаАнотація:
Orientador: Thais Borges Cesar<br>Banca: Amanda Martins Baviera<br>Banca: Luis Carlos Spolidorio<br>Resumo: O estresse oxidativo e a inflamação na obesidade estão associados ao desenvolvimento de doenças crônicas, tais como o diabetes mellitus e as doenças cardiovasculares. A ingestão de dietas com alto teor de gorduras saturadas e açúcar, mas deficientes em compostos antioxidantes, contribui para o acúmulo de tecido adiposo e podem levar ao aumento de marcadores inflamatórios no sangue e tecidos. Os flavonoides cítricos possuem propriedades biológicas capazes de atenuar o estresse oxidativo e a inflamação, protegendo contra as desordens metabólicas decorrentes da obesidade e excesso de tecido adiposo. Neste trabalho foi avaliado o efeito da hesperidina, eriocitrina e eriodictiol sobre a inflamação, o estresse oxidativo e alterações no soro, fígado, coração e baço de camundongos induzidos à obesidade com dieta hiperlipídica, contendo 45% de calorias derivadas de lipídios, por quatro semanas. A hesperidina, eriocitrina e eriodictiol inibiram eficientemente o aumento dos níveis séricos de IL-6, MCP-1, proteína C-reativa, e de TBARS no fígado causado pelo consumo da dieta hiperlipídica e excesso de gordura visceral, impedindo o aumento da massa do baço e aumentando a capacidade antioxidante total no soro. A eriocitrina e eriodictiol reduziram também os níveis de TBARS no soro, enquanto o acúmulo de gordura e danos no fígado foram reduzidos pela hesperidina e eriocitrina, e a massa do coração pela hesperidina e eriodictiol. Esses resultados mostram que a hesperidina, eriocitrina e eriodictiol protegem contra a inflamação e estresse oxidativo causados pelo consumo de dieta hiperlipídica e acúmulo de gordura visceral, como indicado pela diminuição dos marcadores inflamatórios, da peroxidação lipídica, esteatose e danos hepáticos, e da massa do baço e coração, sendo bons candidatos para o tratamento das alterações primárias da obesidade, nas quais eles poderiam ajudar a prevenir o desenvolvimento de ...<br>Abstract: Oxidative stress and inflammation in obesity are associated with the development of chronic diseases such as diabetes mellitus and cardiovascular diseases. The ingestion of diets rich in saturated fatty acids and sugar, but deficient in antioxidants, contributes to adipose tissue accumulation and may lead to increased inflammatory markers in the blood and tissues. Citrus flavonoids have biological properties capable of attenuating oxidative stress and inflammation, protecting against metabolic disorders resulting from obesity and adipose tissue excess. In the present work we assessed the effect of hesperidin, eriocitrin and eriodictyol over inflammation, oxidative stress and the changes resulting from these process in the blood serum, liver, heart and spleen of mice fed a high-fat diet, which contained 45% of calories from fat, for a period of four weeks. Hesperidin, eriocitrin and eriodictyol supplementation efficiently inhibited the increase of serum IL-6, MCP-1 and C-reactive protein, and also the TBARS levels of the liver, caused by high-fat diet ingestion and excessive visceral fat, thus preventing the increase in spleen weight and increasing serum total antioxidant capacity. Eriocitrin and eriodictyol also reduced TBARS levels in the blood serum, while liver fat accumulation and damage were reduced by hesperidin and eriocitrin, and heart weight by hesperidin and eriodictyol. These results show that hesperidin, eriocitrin and eriodictiol have protective effect against inflammation and oxidative stress caused by high-fat diet feeding and visceral obesity, as indicated by reduced liver damage and fat accumulation, and reduced heart and spleen weight, making them good candidates for use in such conditions, in which they could possibly help to prevent cardiovascular diseases ...<br>Mestre
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Ferreira, Paula Souza [UNESP]. "Atividade anti-inflamatória e antioxidante de flavonoides cítricos em camundongos submetidos a dieta indutora do estado pró-inflamatório." Universidade Estadual Paulista (UNESP), 2014. http://hdl.handle.net/11449/113840.
Повний текст джерелаАнотація:
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000797265.pdf: 823819 bytes, checksum: 82bdb4c30be8ca9c7bb831e2a43e8816 (MD5)<br>Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)<br>O estresse oxidativo e a inflamação na obesidade estão associados ao desenvolvimento de doenças crônicas, tais como o diabetes mellitus e as doenças cardiovasculares. A ingestão de dietas com alto teor de gorduras saturadas e açúcar, mas deficientes em compostos antioxidantes, contribui para o acúmulo de tecido adiposo e podem levar ao aumento de marcadores inflamatórios no sangue e tecidos. Os flavonoides cítricos possuem propriedades biológicas capazes de atenuar o estresse oxidativo e a inflamação, protegendo contra as desordens metabólicas decorrentes da obesidade e excesso de tecido adiposo. Neste trabalho foi avaliado o efeito da hesperidina, eriocitrina e eriodictiol sobre a inflamação, o estresse oxidativo e alterações no soro, fígado, coração e baço de camundongos induzidos à obesidade com dieta hiperlipídica, contendo 45% de calorias derivadas de lipídios, por quatro semanas. A hesperidina, eriocitrina e eriodictiol inibiram eficientemente o aumento dos níveis séricos de IL-6, MCP-1, proteína C-reativa, e de TBARS no fígado causado pelo consumo da dieta hiperlipídica e excesso de gordura visceral, impedindo o aumento da massa do baço e aumentando a capacidade antioxidante total no soro. A eriocitrina e eriodictiol reduziram também os níveis de TBARS no soro, enquanto o acúmulo de gordura e danos no fígado foram reduzidos pela hesperidina e eriocitrina, e a massa do coração pela hesperidina e eriodictiol. Esses resultados mostram que a hesperidina, eriocitrina e eriodictiol protegem contra a inflamação e estresse oxidativo causados pelo consumo de dieta hiperlipídica e acúmulo de gordura visceral, como indicado pela diminuição dos marcadores inflamatórios, da peroxidação lipídica, esteatose e danos hepáticos, e da massa do baço e coração, sendo bons candidatos para o tratamento das alterações primárias da obesidade, nas quais eles poderiam ajudar a prevenir o desenvolvimento de ...<br>Oxidative stress and inflammation in obesity are associated with the development of chronic diseases such as diabetes mellitus and cardiovascular diseases. The ingestion of diets rich in saturated fatty acids and sugar, but deficient in antioxidants, contributes to adipose tissue accumulation and may lead to increased inflammatory markers in the blood and tissues. Citrus flavonoids have biological properties capable of attenuating oxidative stress and inflammation, protecting against metabolic disorders resulting from obesity and adipose tissue excess. In the present work we assessed the effect of hesperidin, eriocitrin and eriodictyol over inflammation, oxidative stress and the changes resulting from these process in the blood serum, liver, heart and spleen of mice fed a high-fat diet, which contained 45% of calories from fat, for a period of four weeks. Hesperidin, eriocitrin and eriodictyol supplementation efficiently inhibited the increase of serum IL-6, MCP-1 and C-reactive protein, and also the TBARS levels of the liver, caused by high-fat diet ingestion and excessive visceral fat, thus preventing the increase in spleen weight and increasing serum total antioxidant capacity. Eriocitrin and eriodictyol also reduced TBARS levels in the blood serum, while liver fat accumulation and damage were reduced by hesperidin and eriocitrin, and heart weight by hesperidin and eriodictyol. These results show that hesperidin, eriocitrin and eriodictiol have protective effect against inflammation and oxidative stress caused by high-fat diet feeding and visceral obesity, as indicated by reduced liver damage and fat accumulation, and reduced heart and spleen weight, making them good candidates for use in such conditions, in which they could possibly help to prevent cardiovascular diseases ...
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Kotecki, Claire. "Oxidative stress resistance in drosophila melanogaster." Thesis, Open University, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.527450.
Повний текст джерела
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Anderson, Richard Anthony. "Lipids, oxidative stress and endothelial function." Thesis, King's College London (University of London), 2004. https://kclpure.kcl.ac.uk/portal/en/theses/lipids-oxidative-stress-and-endothelial-function(ca261d48-d716-4156-9a38-dbb72775b36a).html.
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Schock, Bettina C. "Oxidative stress in paediatric lung disease." Thesis, Queen's University Belfast, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300998.
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Sacre, Sandra Michelle. "Endothelial cell annexins and oxidative stress." Thesis, University College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.394510.
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Yusof, Ashril bin. "Exercise-induced oxidative stress in erythrocytes." Thesis, University of Essex, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.434390.
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Jan, Mohamed Hamid Jan. "Iron absorption : control and oxidative stress." Thesis, King's College London (University of London), 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.444192.
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Han, Bing. "Mechanistic Consequences of Cardiac Oxidative Stress." The Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=osu1203478009.
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DHALIWAL, PARVIN. "PARKINSON'S GDNF THERAPY AND OXIDATIVE STRESS." Thesis, The University of Arizona, 2008. http://hdl.handle.net/10150/190438.
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Andrade, Lara Filipe Rocha. "Hereditary hemochromatosis: cellular response to oxidative stress." Master's thesis, Universidade de Aveiro, 2013. http://hdl.handle.net/10773/12495.
Повний текст джерелаАнотація:
Mestrado em Bioquímica - Bioquímica Clínica<br>Iron is a key element for basic cellular functions. If iron homeostasis is not maintained it may lead to iron overload. Patients with Hereditary Hemochromatosis (HH) and with the C282Y HFE mutation have a progressive severe iron overload that, if it is not treated, may lead to tissue damage, that mostly culminate in hepatic cirrhosis and carcinoma. Having in mind that tissue damage in HH may be related with oxidative stress (OS) caused by iron toxicity, it is important to understand in what way the OS defense is acting in cells from HH patients with severe forms of iron overload. Few studies have been performed concerning the eventual prooxidant state in blood cells, which bear a major source of OS. Nevertheless, in a recent study it was shown that cultured lymphocytes (LY) from HH, when compared with cultured LY from controls and patients with secondary forms of hemochromatosis, have an increased protection against chromosome instability (CI) induced by 1,2:3,4 diepoxybutane (DEB) – an OS-related alkylating agent. This suggests an adaptive response of HH cells to the high level of OS. However, it is not known yet if the same response can be observed with other sources of iron toxicity, namely in the presence of bleomycin (BLM), that acts forming a complex with non-transferrin bound iron (NTBI).
In order to better understand the oxidant status of HH blood cells and the putative adaptive response of HH cells to iron toxicity, a study was performed to characterize two selected OS parameters: evaluation of reduced glutathione (GSH) depletion and of lipid peroxidation (LPO). The study was performed in red blood cells (RBC) and lymphocytes (LY), either basal and after 36h in culture, with and without induction of OS. Induction of OS was performed with DEB and with BLM. A second objective of the present work was to test if the previously observed adaptive response of HH cells to DEB-induced OS can also be observed after induction with BLM.
Characterization of the OS parameters was performed in RBC and LY from 5 HH patients with severe iron overload and 6 healthy donors (HD), at day 0 and after 36h of culture, non-treated and treated with DEB or BLM. Studies of CI were performed in BLM-induced LY from the same 5 HH patients and 6 HD.
The results show that RBC from HH patients, compared with those from HD, have a larger GSH depletion and more LPO, either at day 0 and after 36h in culture medium. This suggests an increased level of OS in HH RBC. On the contrary, LY from HH patients present less GSH depletion after 36h of culture than LY from HD, being this effect more pronounced in DEB and BLM-treated cultures. Additionally, LPO levels were decreased in LY from HH patients after 36h of culture when compared with LY from HD. This result suggests that HH cultured LY, either non-treated or treated with DEB and BLM, have a still not completely understood mechanism of defense against OS. BLM-induced CI in cultured LY from HH patients was not different from the observed in cultured LY from HD. Therefore, we can postulate that toxicity induced by BLM did not increased CI in cells from HH patients with severe iron overload.<br>O ferro é um dos elementos chave para as funções celulares básicas. Se a sua homeostasia não for corretamente mantida, poderá ocorrer uma sobrecarga de ferro no organismo. Os doentes com Hemocromatose Hereditária (HH), com a mutação C282Y no gene HFE, possuem uma progressiva e severa sobrecarga de ferro que, se não for tratada, pode levar a dano nos tecidos, podendo mesmo culminar em cirrose hepática e carcinoma. Tendo em conta que o dano tecidular pode estar associado ao stress oxidativo (OS) causado pela sobrecarga de ferro, é importante perceber de que modo atua o sistema de defesa contra o OS nas células dos doentes HH com forma severa de sobrecarga de ferro. Poucos estudos foram realizados sobre o potencial estado oxidante nas células do sangue, onde se encontra uma das maiores fontes de reações oxidativas. Contudo, num estudo recente foi demonstrado que linfócitos de doentes com HH, quando comparados com linfócitos de controlos e pacientes com formas secundárias de hemocromatose, apresentam uma maior proteção relativamente à instabilidade cromossómica (CI) induzida por 1,2:3,4 diepoxibutano (DEB) – um agente alquilante que provoca OS. Este estudo sugere uma resposta adaptativa das células HH a níveis elevados de OS. No entanto, ainda não se sabe se esta mesma resposta pode ser observada com outras fontes de toxicidade do ferro, nomeadamente na presença de bleomicina (BLM) cuja atividade depende da formação de complexos com o ferro não ligado à transferrina (NTBI).
Para compreender melhor o estado oxidante das células do sangue dos doentes HH e a suposta resposta adaptativa das células dos doentes de HH à toxicidade do ferro, foi feita a análise de dois parâmetros de OS selecionados: avaliação da depleção da glutationa reduzida (GSH) e da peroxidação lipídica (LPO). Esta análise foi efetuada em eritrócitos (RBC) e linfócitos (LY), tanto no tempo 0 como passadas 36h em cultura, com ou sem indução de OS. O segundo objetivo deste trabalho foi testar se a BLM promove uma resposta adaptativa à CI comparável à que foi observada com o DEB.
Tanto a caracterização dos parâmetros de OS como os estudos de CI foram efetuados em células de 5 doentes com HH, com elevada sobrecarga de ferro, e em células de 6 dadores saudáveis (HD).
Os resultados mostraram que os RBC dos doentes com HH, comparativamente com os dos HD, apresentam uma maior depleção de GSH e maior LPO, quer ao dia 0 quer após 36h em meio de cultura. Estes resultados sugerem um aumento de OS nos RBC dos doentes. Contrariamente, os LY dos doentes de HH apresentaram menor depleção de GSH após 36h de cultura, sendo esta mais notória nas culturas induzidas com DEB e BLM. Adicionalmente, os níveis de LPO são menores em LY dos doentes de HH, após 36h de cultura, comparativamente com os dos HD. Isto sugere que culturas de LY, quer não-tratadas quer tratadas com DEB ou BLM, têm um algum tipo de mecanismo de defesa contra o OS, ainda não compreendido. A frequência de CI induzida por BLM em LY de doentes com HH não é significativamente diferente da observada em LY de HD, não se observando assim uma diferença na capacidade de resposta à BLM, entre células de doentes e controlos. Pode-se então concluir que a toxicidade induzida por BLM não aumenta a CI em células de doentes com HH com forma severa de sobrecarga de ferro.
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Chang, Hui. "Oxidative stress in the retina an experimental study in the rat /." Lund : Dept. of Ophthalmology, University Hospital, Lund University, 1994. http://catalog.hathitrust.org/api/volumes/oclc/39725792.html.
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Prado, Renato Paschoal [UNESP]. "Influência dos caretonóides, retinol e α-Tocoferol e dos polimorfismos dos genes CYP1A1, GSTP1, MTHFR (A1298C E C6777) E XRCC1 (194Trp E 399 Gln) sobre os níveis de danos oxidativos do DNA, de uracilas incorporadas ao DNA e da capacidade de reparo do DNA". Universidade Estadual Paulista (UNESP), 2013. http://hdl.handle.net/11449/104583.
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prado_rp_dr_botfm.pdf: 1768816 bytes, checksum: 9cf30006e86899d47a461a8d33e92140 (MD5)<br>É crescente o número de estudos que demonstram a importância de micronutrientes e compostos bioativos presentes nos alimentos na prevenção de diversas doenças degenerativas crônicas. Entretanto vários estudos moleculares epidemiológicos têm demonstrado que além de fatores ambientais, como a dieta, essas doenças degenerativas podem ser modulada por genes envolvidos no biometabolismo de xenobióticos, metabolismo do carbono e no reparo de DNA. Portanto, o presente estudo avaliou a possível influência do padrão alimentar e dos polimorfismos dos genes GSTP1, CYP1A1, XRCC1 e MTHFR sobre os níveis de danos oxidativos no DNA, uracilas incorporadas no DNA e eficiência do sistema de reparo de DNA em dois grupos de indivíduos residentes em Botucatu com diferentes padrões alimentares. Grupo I (GI): 87 indivíduos com alimentação rica em produtos orgânicos, grãos integrais, frutas e vegetais, e baixa ingestão de produtos industrializados; Grupo II (GII): 97 indivíduos com alimentação rica em produtos industrializados e pobres em frutas e vegetais. A quantificação do nível de danos oxidativos no DNA, uracilas incorporadas ao DNA e a eficiência do sistema reparo de DNA em linfócitos de sangue periférico, foi analisada utilizando-se o Teste do Ensaio Cometa. Os polimorfismos dos genes GSTP1, CYP1A1, XRCC1 e MTHFR foram analisados por realtime PCR. Também foi realizada a análise dos níveis de luteína, criptoxantina, -caroteno, -caroteno, licopeno, retinol e -tocoferol no plasma, pela técnica de cromatografia líquida de alta pressão (HPLC). Os indivíduos do GI apresentaram menores níveis de danos oxidativos no DNA e menores níveis de dano no DNA induzidos pela H2O2 quando comparados aos indivíduos do GII. Quanto aos subgrupos de micronutrientes: Indivíduos do subgrupo percentil 75 para todos os micronutrientes tiveram maior nível de danos no DNA do que os indivíduos...<br>Not available
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Prado, Renato Paschoal. "Influência dos caretonóides, retinol e α-Tocoferol e dos polimorfismos dos genes CYP1A1, GSTP1, MTHFR (A1298C E C6777) E XRCC1 (194Trp E 399 Gln) sobre os níveis de danos oxidativos do DNA, de uracilas incorporadas ao DNA e da capacidade de reparo do DNA /". Botucatu, 2013. http://hdl.handle.net/11449/104583.
Повний текст джерелаАнотація:
Orientador: Marcelo Sady Plácido Ladeira<br>Banca: Luis Carlos Giarola<br>Banca: Alaor Aparecido Almeida<br>Banca: Aniele Radzikoski Agner<br>Banca: Rodrigo Otávio Alves de Lima<br>Resumo: É crescente o número de estudos que demonstram a importância de micronutrientes e compostos bioativos presentes nos alimentos na prevenção de diversas doenças degenerativas crônicas. Entretanto vários estudos moleculares epidemiológicos têm demonstrado que além de fatores ambientais, como a dieta, essas doenças degenerativas podem ser modulada por genes envolvidos no biometabolismo de xenobióticos, metabolismo do carbono e no reparo de DNA. Portanto, o presente estudo avaliou a possível influência do padrão alimentar e dos polimorfismos dos genes GSTP1, CYP1A1, XRCC1 e MTHFR sobre os níveis de danos oxidativos no DNA, uracilas incorporadas no DNA e eficiência do sistema de reparo de DNA em dois grupos de indivíduos residentes em Botucatu com diferentes padrões alimentares. Grupo I (GI): 87 indivíduos com alimentação rica em produtos orgânicos, grãos integrais, frutas e vegetais, e baixa ingestão de produtos industrializados; Grupo II (GII): 97 indivíduos com alimentação rica em produtos industrializados e pobres em frutas e vegetais. A quantificação do nível de danos oxidativos no DNA, uracilas incorporadas ao DNA e a eficiência do sistema reparo de DNA em linfócitos de sangue periférico, foi analisada utilizando-se o Teste do Ensaio Cometa. Os polimorfismos dos genes GSTP1, CYP1A1, XRCC1 e MTHFR foram analisados por realtime PCR. Também foi realizada a análise dos níveis de luteína, criptoxantina, -caroteno, -caroteno, licopeno, retinol e -tocoferol no plasma, pela técnica de cromatografia líquida de alta pressão (HPLC). Os indivíduos do GI apresentaram menores níveis de danos oxidativos no DNA e menores níveis de dano no DNA induzidos pela H2O2 quando comparados aos indivíduos do GII. Quanto aos subgrupos de micronutrientes: Indivíduos do subgrupo percentil 75 para todos os micronutrientes tiveram maior nível de danos no DNA do que os indivíduos... (Resumo completo, clicar acesso eletrônico abaixo)<br>Abstract: Not available<br>Doutor
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Plant, Stuart D. "The response of human umbilical vein endothelial cells and blood platelets to modified NiTi surfaces." Thesis, University of Nottingham, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275630.
Повний текст джерела
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Murray, Ashley Rebecca. "Oxidative stress in skin induced by chemical and physical agents." Morgantown, W. Va. : [West Virginia University Libraries], 2006. https://eidr.wvu.edu/etd/documentdata.eTD?documentid=4558.
Повний текст джерелаАнотація:
Thesis (Ph. D.)--West Virginia University, 2006.<br>Title from document title page. Document formatted into pages; contains xii, 203 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references.
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Cruz, Daniel Filipe Soares Pereira da. "Lifestyle impact on human sperm oxidative balance." Master's thesis, Universidade de Aveiro, 2014. http://hdl.handle.net/10773/13262.
Повний текст джерелаАнотація:
Mestrado em Biomedicina Molecular<br>Infertility is a clinical condition that affects about 15% of reproductive-aged couples worldwide. Half of these cases are due to male factors. A large percentage of male infertility cases are idiopathic, however, in the last years the influence of oxidative stress in decreased semen quality has been discussed. The lifestyle, including consumption of alcohol, tobacco, drugs and the alteration in circadian cycle, has been proposed as responsible for the increase of reactive oxygen species (ROS). This increase leads to an alteration of the balance between oxidants and antioxidant defenses present in the organism, causing oxidative stress. High levels of ROS damage biomolecules – DNA, proteins or lipids – present in sperm cells and may lead to the loss of membrane integrity, DNA fragmentation or even to death by apoptosis.
The aims of the thesis was to evaluate the influence of acute lifestyle changes on oxidative balance of sperm cells. Therefore, we analyzed the antioxidant capacity of the sperm, as well as the presence of certain antioxidant proteins, by colorimetric techniques and immunoblotting. We also evaluated the effect of ROS by measuring the protein oxidation. The seminal quality was evaluated by performing a routine semen analysis.
The results indicate that there is a relationship between the changes in lifestyle and the amount of antioxidants in sperm, and the most reported change involved the protein superoxide dismutase (SOD). It was also demonstrated that the variation in protein oxidation levels is dependent on the consumption of alcohol and nicotine.
In this study it was concluded that oxidative balance of sperm cells is affected by lifestyle changes; in turn, oxidative balance changes is then reflected in semen quality.<br>A infertilidade é um problema clínico que afeta cerca de 15% dos casais em idade fértil. Metade dos casos de infertilidade deve-se a fatores masculinos, sendo que uma grande percentagem tem origem idiopática. Nos últimos anos tem-se discutido a influência do stress oxidativo na diminuição da qualidade seminal. O estilo de vida, nomeadamente o consumo de álcool e tabaco têm sido fatores propostos como responsáveis pelo aumento de espécies reativas de oxigénio (ROS), levando a uma alteração do equilíbrio entre os oxidantes e as defesas antioxidantes presentes no organismo, causando stress oxidativo. Níveis aumentados de ROS danificam as biomoléculas – DNA, proteínas ou lípidos – presentes nos espermatozoides, podendo levar à perda da integridade da membrana, à fragmentação de DNA ou até mesmo à morte por apoptose.
Este estudo tem como objetivo avaliar a influência da alteração aguda do estilo de vida no equilíbrio oxidativo dos espermatozoides. Desta forma, foi analisada a capacidade antioxidante dos espermatozoides, bem como a presença de certas proteínas antioxidantes, através de técnicas colorimétricas e de immunoblotting. Foi também avaliado o efeito das ROS através da medição de oxidação proteica. A qualidade seminal foi avaliada através da realização de espermogramas.
Os resultados obtidos indicam que existe uma relação entre as alterações do estilo de vida e a quantidade de antioxidantes no espermatozoide, sendo que a alteração mais marcada envolveu a proteína superóxido dismutase (SOD). Foi também detetado uma variação dos níveis de oxidação proteica, dependente da alteração dos consumos de álcool e nicotina.
Com este trabalho concluiu-se que o equilíbrio oxidativo dos espermatozoides é afetado pelas alterações no estilo de vida, sendo que a alteração deste equilíbrio reflete-se posteriormente na qualidade seminal.
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Hammerman, Malin. "Oxidative Stress and Protein Acetylation in Adipocytes." Thesis, Linköpings universitet, Proteinkemi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-75785.
Повний текст джерелаАнотація:
Obesity is an increasing health problem which is causally associated with insulin resistance and type 2 diabetes. Oxidative stress, i.e. overproduction of reactive oxygen species, is associated with insulin resistance and obesity and may be a major risk factor in the onset and progression of diabetes. Bernlohr Lab at University of Minnesota have study oxidative stress in adipocytes by silencing the enzyme glutathione S-transferase A-4 (GSTA4), an enzyme detoxifying 4-hydroxynonenal formed during oxidative stress. Their results indicate that lysine acetylation, an important post-translational modification, may be involved during oxidative stress. In this study lysine acetylation has been investigated in condition of oxidative stress in 3T3-L1 adipocytes and subcutaneous adipose tissue from mice using SDS-PAGE gel electrophoresis and western blot. Lysine acetylation was analyzed in different compartments of the cell such as in cytoplasm, mitochondria as well as in whole cell extracts. Silencing of GSTA4 and stimulation by TNF-α in 3T3-L1 adipocytes resulted in an increase of lysine acetylation in cytoplasm. Furthermore, stimulation by IL-6 did not have any effect on lysine acetylation. Surprisingly, subcutaneous adipose tissue from mice fed on a high-fat diet showed a decrease of lysine acetylation in cytoplasm compare to mice fed on a chow diet. In conclusion, lysine acetylation seems to change during oxidative stress and may be an important factor during insulin resistance, type 2 diabetes and obesity. Therefore, studying lysine acetylation and enzymes modulating acetylation may potentially increase our understanding of insulin resistance, type 2 diabetes and obesity and could lead to new therapies.
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Sova, H. (Henri). "Oxidative stress in breast and gynaecological carcinogenesis." Doctoral thesis, Oulun yliopisto, 2014. http://urn.fi/urn:isbn:9789526204062.
Повний текст джерелаАнотація:
Abstract Cancer is the leading cause of death worldwide. Despite the significant research effort, underlying mechanisms of carcinogenic processes are still poorly understood. In recent decades, a group of extremely reactive oxygen metabolites, reactive oxygen species (ROS), have been linked closely to carcinogenesis. Levels of ROS are constantly controlled by antioxidants to ensure stable redox balance in our cells. An aberrant cellular redox balance is thought to be connected to carcinogenesis by inflicting damage to cellular macromolecules and disturbing normal cellular signalling. In this work, the role of ROS in carcinogenesis was studied by observing the ROS-derived DNA damage marker 8-hydroxydeoxyguanosine (8-OHdG) in breast cancer and endometriosis-associated ovarian cancer. This marker was also measured in connection with endometriosis and PCOS to study the early stages of the carcinogenic process. In addition, peroxiredoxin antioxidant enzymes were studied in endometriosis-associated ovarian cancer to explore their impact on the carcinogenic process and relationship with ROS-derived DNA damage. There seems to be a decreasing trend in the expression of 8-OHdG in the development of breast cancer and endometriosis-associated ovarian cancer. In breast cancer, low levels of 8-OHdG in serum and in tumour tissue were found to be associated with more aggressive disease. In endometriosis-associated ovarian cancer, 8-OHdG and Prx II expressions in tissue decreased with malignant transformation from benign endometriosis tissue to ovarian cancer. Patients with PCOS were found to have lower levels of 8-OHdG in serum compared with healthy controls and metformin treatment further decreased 8-OHdG levels in obese patients. These results, together with observations is previous studies indicate that in breast cancer and endometriosis-associated ovarian cancer, a high level of ROS-derived DNA damage could be significant factor in the initiation stage of carcinogenesis, whereas in later stages carcinomas benefit from lower ROS levels that support tumour growth and survival via cellular signalling. In endometriosis, there seem to be high amounts of ROS-derived DNA damage, which could explain the increased ovarian cancer risk, while in PCOS, aberrant ROS levels could contribute to the pathogenesis of the disease itself and also to possible cancer incidence by inducing abnormal cellular signalling<br>Tiivistelmä Syöpä on nykyisin maailman yleisin kuolinsyy. Vaikka syöpätutkimukseen kohdistetaan maailmanlaajuisesti huomattavia resursseja, syövän kehittymisen perimmäinen syy on edelleen heikosti tunnettu. Yhä kasvavan todistusaineiston perusteella happiradikaalien epäillään liittyvän läheisesti syövän kehittymiseen. Nämä erittäin reaktiiviset hapen aineenvaihduntatuotteet ovat välttämättömiä solujemme normaalille toiminnalle, mutta liian suurina määrinä ne voivat vaurioittaa solun rakenteita ja häiritä solun normaalia viestintää. Solut sisältävät useita antioksidantteja, joiden tärkeimpänä tehtävänä on kontrolloida happiradikaalien määrää ja näin ylläpitää solun hapetus-pelkistys -tasapaino. Tässä väitöskirjatutkimuksessa tutkittiin happiradikaalien yhteyttä syövän kehittymiseen tarkastelemalla niiden aiheuttaman DNA-vaurion merkkiainetta, 8-hydroksideoksiguanosiinia (8-OHdG), rintasyövässä ja endometrioosiin liittyvässä munasarjasyövässä sekä peroksiredoksiiniperheen antioksidanttientsyymejä endometrioosiin liittyvässä munasarjasyövässä. 8-OHdG:n avulla selvitettiin myös munasarjojen monirakkulaoireyhtymän (PCOS) ja endometrioosin yhteyttä syövän kehittymiseen. Lisäksi tutkittiin metformiinin vaikutusta happiradikaalien aiheuttamaan DNA-vaurioon. Väitöskirjatutkimuksen tulosten perusteella 8-OHdG:n määrä vähentyy rintasyövän edetessä ja endometrioosiin liittyvän munasarjasyövän kehittyessä. Matalat 8-OHdG -tasot syöpäkudoksessa ja verinäytteissä ovat yhteydessä aggressiivisempaan taudinkuvaan rintasyövässä. Endometrioosiin liittyvässä munasarjasyövässä kudoksen ilmentämä 8-OHdG ja Prx II vähentyi asteittain siirryttäessä hyvänlaatuisesta endometrioosista munasarjasyöpään. Munasarjojen monirakkulaoireyhtymässä potilaiden verinäytteiden 8-OHdG -tasot olivat merkittävästi matalammat terveisiin verrokkeihin verrattuna. Korkeilla happiradikaalipitoisuuksilla ja niistä aiheutuvalla DNA-vauriolla on väitöskirjatutkimuksen tulosten perusteella tärkeä rooli syövän syntyvaiheessa, kun taas syövän myöhemmissä kehitysvaiheissa matalat happiradikaalipitoisuudet tukevat syövän kasvua ja selviytymistä soluviestinnän avulla. Endometrioosipotilaiden kohonnut munasarjasyöpäriski vaikuttaisi olevan seurausta runsaasta happiradikaalien aiheuttamasta DNA-vauriosta endometrioosikudoksessa. Munasarjojen monirakkulaoireyhtymässä poikkeavien happiradikaalitasojen aiheuttama puutteellinen soluviestintä liittyy mahdollisesti taudin patogeneesiin ja syöpäriskiin
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Flint, Annika. "The Oxidative Stress Defenses of Campylobacter jejuni." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/32073.
Повний текст джерелаАнотація:
Campylobacter jejuni infection is one of the leading causes of gastroenteritis in humans worldwide. During colonization of the gastrointestinal tract, C. jejuni will be unavoidably exposed to reactive oxygen species (ROS) produced by the host immune system and other intestinal microbiota. Identification of defenses against ROS is therefore important for understanding how Campylobacter survives this environmental stress during infection. Construction of isogenic deletion mutants into genes encoding potential oxidative stress defense systems followed by phenotypic screening revealed genes important for oxidant defense within C. jejuni. Surprisingly, genes involved in motility were found to play an indirect role in resistance to oxidative stress. Deletion of the flagellar motor apparatus genes, motAB, resulted in increased sensitivity towards superoxide which could be restored by fumarate supplementation or tandem deletion of motAB with ccoQ (cytochrome c oxidase). This finding suggested that disruption of the proton gradient across the inner membrane resulted in increased superoxide production in non-motile flagellar mutants. Phenotypic screening of the mutant library also identified a novel gene (cj1386) specifically involved in hydrogen peroxide defense within the cell. Hydrogen peroxide detoxification within living organisms is predominantly carried out by catalase enzymes. Interestingly, cj1386 is located directly downstream from katA (catalase) in the C. jejuni genome and it was found that a ∆cj1386 mutant had reduced catalase activity relative to wild-type C. jejuni. Immunoprecipitation of KatA from ∆cj1386 revealed a significant reduction in hemin content associated with KatA suggesting a role for cj1386 in hemin trafficking to KatA. Hemin binding experiments with purified Cj1386 demonstrated the ability of Cj1386 to bind hemin with a 1:1 hemin-to-protein binding ratio. Furthermore, co-immunoprecipitation experiments revealed an interaction between KatA and Cj1386. Mutagenesis of conserved amino acids in Cj1386 demonstrated that tyrosine 57 plays an important role in hemin affinity and is required for proper hemin content of KatA within the cell. Overall, this work provides a global characterization of key oxidant defenses within C. jejuni and provides one of the first studies investigating hemin trafficking to KatA.
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Li, Wei Beck Melinda A. "Nutritionally-induced oxidative stress and viral infection." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2006. http://dc.lib.unc.edu/u?/etd,523.
Повний текст джерелаАнотація:
Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2006.<br>Title from electronic title page (viewed Oct. 10, 2007). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Nutrition." Discipline: Nutrition; Department/School: Public Health.
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Renganathan, Kutralanathan. "Oxidative stress and age related macular degeneration." online version, 2008. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1193002743.
Повний текст джерела
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Garlick, Andrew P. "Carbohydrate metabolism during oxidative stress in plants." Thesis, University of Oxford, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.270014.
Повний текст джерела
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Watt, Jonathan. "Targeting oxidative stress after percutaneous coronary intervention." Thesis, University of Glasgow, 2011. http://theses.gla.ac.uk/2877/.
Повний текст джерелаАнотація:
Percutaneous coronary intervention (PCI) improves the blood supply to the heart by unblocking narrowed coronary arteries. Implantation of a coronary stent is usually required to scaffold the artery and improve long-term vessel patency. Drug-eluting stents (DES) have been developed to decrease the incidence of stent renarrowing, known as in-stent restenosis (ISR), the main limitation of bare metal stents (BMS). DES release potent drugs into the artery wall to inhibit cell division and attenuate ISR. However, this strategy can also impair vascular healing and increase the risk of stent thrombosis, which is a serious concern. Novel approaches to this problem are urgently required. Oxidative stress reflects a state in which reactive oxygen species (ROS) prevail over antioxidant defences. PCI causes a major release of ROS from the injured artery wall and these molecules appear to play an important role in critical signalling pathways involved in vascular repair. Numerous animal studies have found that oral antioxidants may reduce ISR and improve healing, yet these strategies have not been effective in humans. Stent-based delivery of antioxidants may offer more efficacious, targeted protection against oxidative stress than oral administration. The role of oxidative stress in endothelial repair mediated by bone marrow-derived endothelial progenitor cells (EPCs) in patients with coronary heart disease is also poorly defined. The main aims of this thesis were: to determine the in vitro effects of oxidative stress on key aspects of thrombosis and vascular healing; to evaluate a novel antioxidant-eluting stent in an in vivo porcine model; and to examine the relationship between oxidised low-density lipoprotein (oxLDL), EPCs and coronary endothelial function in patients with stable angina. Oxidative stress, generated by the xanthine/xanthine oxidase reaction, inhibited whole blood aggregation in a concentration-dependent fashion. This was probably due to an excess of ROS which impaired, rather than stimulated, thrombosis. Healthy endothelial cells (ECs) also inhibited whole blood aggregation, but this was not mitigated by oxidative stress. EC migration was assessed using an in vitro endothelial wound scratch assay. Oxidative stress was highly toxic to ECs and inhibited migratory activity. Nitrone D, a novel spin trapping antioxidant, was evaluated for its suitability as a novel DES coating. Nitrone D displayed weak antithrombotic effects, but markedly inhibited EC migration. Nitrone D was therefore unsuitable for a DES that was intended to improve re-endothelialisation. Oral probucol has established efficacy in animal models of restenosis, but not in humans. Probucol has been successfully incorporated as a dual DES coating with rapamycin in clinical trials. Succinobucol is a novel derivative of probucol with more potent antioxidant, anti-inflammatory and antiproliferative effects. A novel polymer-free succinobucol-eluting stent (SES) and succinobucol/rapamycin-eluting stent (SRES) were developed and compared to a commercially available polymer-free rapamycin-eluting stent (RES) and BMS. Pharmacokinetic studies demonstrated optimal drug elution from the SES. However, in a porcine coronary model, the SES significantly increased neointimal thickness and aggravated ISR. The RES reduced neointimal thickness non-significantly, whereas the SRES caused no difference in neointimal thickness, compared with the BMS. The SES was associated with greater inflammation and persistent fibrin deposition around the stent struts, which are signs of defective healing. There were no significant differences in endothelial regeneration between the groups. Subsequent cell culture studies found that succinobucol was toxic to ECs and smooth muscle cells. In the clinical study, circulating levels of EPCs were strongly correlated with coronary endothelial function, which is a novel finding. Plasma oxLDL levels were not correlated with EPCs or coronary endothelial function. In conclusion, ROS reflect a large array of molecules released after PCI that are multi-faceted regulators of platelets and vascular cells. As such, they represent a complex target for novel DES technologies. Excessive ROS may inhibit thrombus formation and delay re-endothelialisation. However, potent antioxidants delivered to injured arterial tissue after PCI may not necessarily encourage the physiological processes required to accelerate vascular repair. At high dose, local delivery of antioxidants may actually promote inflammation and aggravate ISR. Although oxLDL is known to induce endothelial dysfunction, it is not correlated with the number of circulating EPCs. These findings underline the complicated role of oxidative stress in vascular repair after PCI. Further studies are required to clarify whether antioxidants will ever provide advantages over existing options in the rapidly evolving field of interventional cardiology.
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Thomson, Katrina. "Investigating and detecting biomarkers for oxidative stress." Thesis, University of Glasgow, 2011. http://theses.gla.ac.uk/2408/.
Повний текст джерелаАнотація:
It is widely reported that during periods of inflammation the heme enzyme, myeloperoxidase is generated by macrophages producing reactive oxidative species. Oxidative stress is the imbalance of these oxidative species which will lead to the post translational modification of proteins. Some biomarkers are proteins or post translational modifications that can be used to indicate disease and are becoming increasingly important particularly for the study of progressive diseases. Analysis of biomarkers in bodily fluids will not only be faster and less invasive than a biopsy but will also diagnose disease at an earlier stage and allow disease treatment and progression to be monitored. Known biomarkers for the production of myeloperoxidase are chlorotyrosine and nitrotyrosine. Elevated levels of chlorotyrosine and nitrotyrosine are indicative of atherosclerosis. The early diagnosis of atherosclerosis is important as the onset of this disease can occur at a young age and be asymptomatic until later, more developed stages. Here I aim to develop sensitive methods of detection for these biomarkers in a hope that they can be used to classify disease. A Qtrap mass spectrometer is employed with precursor scan for the selective and sensitive detection of chlorotyrosine modifications in in vitro HOCl modified 9 protein mix samples. Compared to a conventional MSMS experiment the precursor scan detects more chlorotyrosine modifications suggesting it is a better method for the detection of post translational modifications. Additionally the precursor scan can be used when there is no prior knowledge of the modification sites. A multiple reaction monitoring method was developed from the MSMS analysis of in vitro chemical modification of human serum albumin and plasma samples. Observations from the MSMS analysis were employed to write the multiple reaction monitoring method to target for chloro- and nitrotyrosine modified peptides of the human serum albumin protein in plasma samples. Detection of these modified peptides was indicated by the common elution of three transitions specific to the peptides precursor mass. Where anomalous peaks of one transition were seen it was known that this was not the elution of the targeted peptide. The use of three transition masses instead of one reduces the generation of false positives. Where more than one peak for the common elution time was seen for a targeted peptide in the chromatography gradient the retention times were used for identification. Peptides are separated by liquid chromatography prior to their analysis on the Qtrap by their hydrophobicity or their polarity. When a peptide becomes chloro- or nitrotyrosine modified the peptide becomes less polar and therefore is seen later in the gradient than in the unmodified state. The observation of more than one peak where the three transitions are seen to be commonly eluted was caused by break-through of signal from poor selection of a m/z value in Q1. The multiple reaction method developed from the analysis of in vitro chemically modified human serum albumin and plasma was then applied for the analysis of clinical samples in the hope that the chloro- and nitrotyrosine modified peptides targeted for in the samples could be used to classify disease. The clinical plasma samples were sourced from 12 healthy volunteers and 12 diseased cardiovascular patients. The multiple reaction monitoring method indicated the modification of peptides and the presence of these modified peptides was confirmed using targeted MSMS. Classification of these samples was not successful and it was thought that a combination of biomarkers is required for the classification of disease.
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Costa, N. J. "Mitochondrial protein thiol modifications during oxidative stress." Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.598052.
Повний текст джерелаАнотація:
The focus of this thesis is to investigate the interactions of mitochondrial protein thiols with ROS and examine the oxidation of these thiols in response to oxidative stress. Among these protein thiol modifications, an area of great interest is the interactions of mitochondrial protein thiols with glutathione, therefore possible connections between the modifications and cell death were investigated. I explored the possibility that staurosporine (STS) induces apoptosis via the mitochondrial pathway, causing early changes in the mitochondrial membrane potential (Δψ), by changing the thiol redox status of the cell. The hypothesis tested was that there may be a common link between oxidative stress and thiol changes of mitochondrial proteins and oxidation of the cellular glutathione pool which then initiates the critical mitochondrial events that lead to apoptosis. STS caused apoptosis after 2-4 hours of treatment and caused a decrease in total glutathione measured in cells, with the depletion of cellular glutathione occurring after the induction of apoptosis. There were no changes in glutathione (GSH)/glutathione disulphide (GSSG) redox state up to one hour of STS treatment, and thus no association of cellular GSH oxidation with the early mitochondrial Δψ changes observed. However, the GSH pool was significantly oxidised after 2 hours. Even so, no significant changes in protein glutathionylation by STS were observed at 2 hours. I next explored the possibility that protein thiol modifications might respond to oxidative stress for the purpose of redox signalling, whereby redox-sensitive modifications might contribute to biological regulation. Therefore, I went on to quantify total and exposed protein thiols in subcellular fractions including mitochondria. This analysis showed that 74% of total liver cell lysate protein thiols are exposed compared to 57% of mitochondrial proteins, 67% of cytosolic proteins and 62% of soluble proteins. The amount of exposed thiols as a percentage of total thiols in each of the four fractions did not differ when comparing rat liver and rat heart tissue. I then further characterised the distribution of protein thiols in the mitochondria and found that approximately two-thirds of protein thiols present in the mitochondrial membrane fraction were exposed compared to 78% in the mitochondrial matrix fraction. In addition, by using two membrane-impermeant thiol-alkylating agents, I was able to show that approximately a third of all the exposed protein thiols in the mitochondrial membrane fraction were either on the outer membrane, facing outward into the cytosol or facing inward into the intermembrane space, within the intermembrane space itself or on the outer leaflet of the inner membrane. The possibility that protein thiols might have a protective role acting as a redox buffer was also explored, and loss of exposed protein thiols during oxidative stress was investigated.
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Wallace, Shona M. "The role of metallothionein in oxidative stress." Thesis, University of Aberdeen, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.318980.
Повний текст джерелаАнотація:
A cell culture model was developed to examine the role of metallothionein in oxidative stress. Chinese hamster ovary cells, which contain little endogenous metallothionein, were transfected with a metallothionein-expressing gene. Metallothionein content of the resultant cell lines ranged from a physiological level to a very high level. The major antioxidant enzyme activities did not vary between the cell lines. Glutathione content, and the proportion of glutathione that was oxidised, was higher than that of the wild type in one of the cell lines, indicating that this cell line had a different phenotype from the wild type, which would affect its response to oxidative stress. Evidence gained from the metallothionein-enriched cells in which glutathione was unaltered from the wild type, indicated a protective effect of metallothionein against oxidative stress. In these cell lines high levels of metallothionein protected the cell against membrane-lysing effects of <I>tert</I>-butyl hydroperoxide (tBuOOH) and menadione sodium bisulphite (MSB). Physiological levels of metallothionein protected cells against tBuOOH. Metallothionein failed to protect DNA against tBuOOH or ferric chloride, but afforded protection to DNA against MSB or cupric chloride, agents with which it can form a conjugate or complex. This suggests that metallothionein was probably located in the cytoplasm, where it was able to scavenge free radicals and reactive oxygen species, thus protecting cytoplasmic components. It only affords protection to DNA when it can prevent the damaging agent from reaching the target site by conjugation or complexing. The cell line with altered phenotype from the wild type, exhibited an enhanced sensitivity to oxidative stress, despite high metallothionein content. Thus a protective role of metallothionein is dependent on the phenotype of the cell.
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Gavriilidis, Christos. "Mitochondrial dysfunction and oxidative stress in osteoarthritis." Thesis, University of Newcastle upon Tyne, 2012. http://hdl.handle.net/10443/1599.
Повний текст джерелаАнотація:
Mitochondria are considered the powerhouse of the cell being the major site of ATP production but in addition to this function they also regulate ROS production and inhibition, calcium handling and apoptosis. Previous studies have reported a downregulation in the levels of superoxide dismutase 2 (SOD2), an inhibitor of mitochondrial superoxide (O2--), in osteoarthritic (OA) hip cartilage compared to that from healthy joints (neck of femur fracture; NOF). This finding provides the opportunity to characterise the functional effects of SOD2 downregulation in OA in the context of oxidative damage and mitochondrial dysfunction. SOD2 depletion increased the mitochondrial O2-- levels in human articular chondrocytes (HAC). Measurement of lipid peroxidation levels in OA and NOF cartilage showed that OA cartilage has higher levels of lipid peroxidation compared to NOF. SOD2 depletion in a chondrosarcoma cell-line, SW1353, also led to a significant increase in lipid peroxidation levels. Additionally, SOD2 depletion led to a significant increase in mtDNA strand breaks in SW1353 cells although there was no difference detected in OA compared to NOF mtDNA. However, large-scale mtDNA deletions were identified in OA cartilage and other OA joint tissues but the low levels of mutated mtDNA observed were not considered to be pathologically relevant. Mitochondrial respiratory function was also determined in OA and NOF isolated chondrocytes. OA chondrocytes showed less spare respiratory capacity (SRC), higher non-phosphorylating respiration and higher proton leak compared to NOF. SOD2-depleted HAC also showed a lower SRC and higher proton leak. Additionally, HAC demonstrated a very low mitochondrial/glycolysis ratio, suggesting that HAC are highly glycolytic cells. SOD2 depletion caused depolarization of the Δψm. NLRX1, a mitochondrially localised gene involved in innate immunity signalling was also identified to regulate basal levels of matrix metalloproteinase 13 (MMP-13) and double stranded RNA- induced ROS levels in chondrocytes. These findings suggest that SOD2 depletion in chondrocytes leads to oxidative damage and mitochondrial dysfunction caused by increasing ROS levels and can potentially lead towards alterations in cell signalling pathways, cellular dysfunction and cartilage degradation.
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Honn, Marie. "The oxidative stress response of Francisella tularensis." Doctoral thesis, Umeå universitet, Klinisk bakteriologi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-115635.
Повний текст джерелаАнотація:
Francisella tularensis is capable of infecting numerous cell types, including professional phagocytes. Upon phagocytosis, F. tularensis resides within the phagosome before escaping into the cytosol to replicate. Phagocytes constitute a hostile environment rich in ROS, which are employed as a means of killing pathogens. ROS interact with and disrupt the function of vital molecules such as DNA, proteins and bacterial structures. Iron potentiates the danger of ROS through the Fenton reaction where ferrous iron reduces H2O2 causing the formation of highly reactive hydroxyl radicals and anions. Low levels of ROS are formed during normal aerobic metabolism and pathogens thus have a need for defense mechanisms to handle the ever present levels of ROS but even more so to combat the onslaught of ROS experienced within a host. This thesis was focused on the investigation of the iron status and oxidative stress response of F. tularensis; thereby identifying key players controlling the bacterial iron content, its adaptation to oxygen-rich environments and defense against ROS. We identified subspecies-specific differences in iron content, where F. tularensis subsp. tularensis was found to contain significantly less iron than strains of subsp. holarctica. The reduced iron content resulted in an increased tolerance to H2O2, despite simultaneously causing a decrease in the activity of catalase - the iron-dependent enzyme responsible for degrading H2O2 in F. tularensis. This strongly suggests that the restricted iron uptake and storage by subsp. tularensis strains is beneficial by rendering the bacteria less susceptible to H2O2, thereby evading the toxic effects of the iron-driven Fenton reaction. This evasion is likely to be an important part of the higher virulence displayed by subsp. tularensis as compared to subsp. holarctica. We further identified that the global regulator, MglA, is important for the adaptation of LVS to oxygen-rich environments. Deletion of mglA from LVS resulted in a mutant, ΔmglA, with impaired defense to oxidative stress, as manifested by an inability to grow to wild-type levels under aerobic conditions, an accumulation of proteins with oxidative damage, a suppressed expression of iron-uptake related genes, an increased catalase activity, and an increased tolerance to H2O2. This phenotype was reversed in a microaerobic environment. We therefore conclude that MglA is an important factor for the defense of LVS to oxidative damage under aerobic conditions and speculate that MglA is of greatest importance in oxygen-rich foci. We also studied the role of OxyR in LVS by creating a ΔoxyR mutant as well as a double mutant, ΔoxyR/ΔkatG. The in vitro response of these mutants, as well as of ΔkatG, to defined ROS was assessed using H2O2, the O2- generating agent paraquat, and the ONOO- generator SIN-1. ΔoxyR was more susceptible to all ROS than LVS as was ΔkatG, with the exception of O2- Strikingly, ΔoxyR/ΔkatG was significantly more susceptible to all ROS tested compared to either single deletion mutant. LVS, ΔoxyR and ΔkatG replicated efficiently in bone marrow-derived macrophages whereas ΔoxyR/ΔkatG showed no replication. In mice, the ΔoxyR mutant displayed impaired replication in liver, but intact replication vs. LVS in spleen. Collectively, our results demonstrate an important role of OxyR in the oxidative stress response and virulence of F. tularensis, and further reveal overlapping roles of OxyR and catalase in the defense against ROS. The results thus shed new light on the complexity of ROS defense in F. tularensis.
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Al, Jothery Aqeel Handil Tarish. "Lactation and oxidative stress in small mammals." Thesis, University of Aberdeen, 2014. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=215095.
Повний текст джерелаАнотація:
During peak lactation female mammals reach a limit in their maximal sustained energy intake (SusEI). The causes of such limits is disputed. In this thesis, I examined the causes of the limits on SusEI at peak lactation, and then explored the consequences of such limits for reproductive performance. Finally I tested a possible physiological mechanism that may underpin the trade-off between reproduction and somatic protection (the oxidative stress theory). To answer these questions, I studied reproductive performance and oxidative stress in two lines of mice previously selected for high and low food intake (MH and ML, respectively). I found that these mice reached a plateau in their food intake around day 13 of lactation. In support of the heat dissipation limits theory, reproductive performance in the MH mice was significantly higher than that of the ML mice. Oxidative damage is expected to be higher among lactating individuals. Moreover, lactating mice with greater reproductive performance are also predicted to experience more oxidative damage. By measuring multiple-markers of oxidative damage and protection in different tissues, I found that lactation resulted in reduced oxidative damage in both brain and serum. Additionally, it did not increase oxidative damage to proteins and DNA in liver. Moreover, multiple measures of oxidative stress in the mammary gland were not significantly different between mice with different reproductive effort. Furthermore, I found that lactating mice with greater reproductive performance (litter size and litter mass) had reduced protein damage in their livers and upregulated protection (HSP70) in their brains. These results were inconsistent with the oxidative stress theory. Finally, I employed a novel approach to assess oxidative stress differences with metabolomics analysis. I found that lactation resulted in significant differences in the metabolome. By focusing on the metabolites that are related to vi oxidative stress, I found that most of these metabolites measured in livers and brains were not affected by lactation which provides more evidence against the oxidative stress theory. My results provide support for the heat dissipation theory as a mechanism explaining the limits on reproductive performance. Moreover it provides comprehensive information against oxidative stress as a mediator of life history trade-offs.
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Dewar, Mairead. "Oxidative stress and cardiovascular ageing in diabetes." Thesis, University of Leicester, 2004. http://hdl.handle.net/2381/29910.
Повний текст джерелаАнотація:
Oxidative stress is thought to be elevated in diabetes as a consequence of hyperglycaemia. This thesis investigates oxidative DNA damage in diabetes, which may contribute to accelerated vascular ageing. Telomeric and mitochondrial DNA are two areas of the genome that may be more susceptible to oxidative stress and were therefore investigated.;51 patients with diabetes (aged 31-78 years) and 101 healthy controls (aged 19-75 years) were recruited. 51 of the controls were age- and sex-matched to be patient group. For both populations physiological profiles were obtained and pulse wave velocity (PWV), an index of vascular stiffness, was measured. Oxidative DNA damage was also investigated in peripheral blood using the comet assay, and in more depth by measuring terminal restriction fragment (TRF) lengths and quantifying mitochondrial DNA (mtDNA) content. PWV increased with age in both study groups (p<0.001) and was significantly higher in the patient group (8.00 +/- 2.89 versus 7.29 +/- 1.64 m/s; p=0.006), suggesting accelerated vascular ageing in diabetes. This was accompanied by elevated levels of oxidative DNA damage; 25.81 +/- 1.18 versus 21.40 +/- 0.81% Tail DNA (p=0.003) in patients and controls respectively. TRF length inversely correlated with age in both groups (p<0.05), with similar rates of attrition, and although they were shorter in the patients with diabetes, this was not significant (p=0.10). Quantification of mtDNA revealed significantly lower levels in the patients with diabetes compared to the controls (0.014 versus 0.016; p=0.020). There is accelerated vascular ageing in diabetes, which is accompanied by elevated oxidative DNA damage, and a decrease in mtDNA, but no alteration in TRF length compared to a healthy control population. The mechanisms underlying these alterations are unknown with the lack of correlations with glycaemic control suggesting it is not the sole cause but it may still contribute.
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Mota, Martorell Natàlia. "Oxidative stress homeostasis and longevity in mammals." Doctoral thesis, Universitat de Lleida, 2021. http://hdl.handle.net/10803/672775.
Повний текст джерелаАнотація:
Les espècies més longeves han evolucionat disminuint la producció endògena d’espècies reactives d’oxigen i proveint-se d’estructures resistents a la oxidació. Per tant, aquelles espècies que viuen més gaudeixen de mitocòndries metabòlicament més eficients i estructuralment més estables. De fet, característiques fenotípiques de la longevitat inclouen la reducció del contingut del complex I i dels aminoàcids sulfurats. Aleshores, l’activitat de determinades vies de senyalització intracel·lulars juga un paper clau regulant l’expressió de gens associats a un fenotip longeu.
En aquest context, aquesta tesi pretén determinar i) la modulació de determinades subunitats del complex I associada a la longevitat; ii) els canvis en el contingut dels aminoàcids sulfurats i els seus intermediaris metabòlics en teixits post-mitòtics i iii) plasma d’espècies més longeves; iv) la regulació del contingut dels diferents elements específics del complex 1 de mTOR en termes de longevitat; i v) l’existència un perfil metabòlic associat a humans de longevitat extrema.
Els resultats obtinguts mostren l’existència de perfils metabòlics associats a la longevitat de les espècies que, en alguns casos, són diferents a aquells perfils associats a la longevitat individual. A més, les espècies més longeves han evolucionat disminuint el contingut de determinades subunitats del complex I que podrien ésser responsables de la menor producció d’espècies reactives d’oxigen. Per altra banda, existeixen factors genètics que podrien determinar l’activitat basal de mTORC1, i que podrien, almenys en part, explicar el fenotip associat a la longevitat. Per tant, sembla que l’assoliment d’una major longevitat implica una adaptació metabòlica i estructural.<br>Las especies más longevas han evolucionado disminuyendo la producción endógena de especies reactivas de oxígeno y proveyéndose de estructuras resistentes a la oxidación. Por lo tanto, aquellas especies que viven más disfrutan de mitocondrias metabólicamente más eficientes y estructuralmente más estables. De hecho, características fenotípicas de la longevidad incluyen la reducción del contenido del complejo I y de amino ácidos sulfurados. Por lo tanto, la activad de determinadas vías de señalización intracelular juegan un papel clave regulando la expresión de genes asociados a un fenotipo longevo.
En este contexto, esta tesis pretende determinar i) la modulación de determinadas subunidades del complejo I asociada a la longevidad; ii) los cambios en el contenido de amino acido sulfurados y de sus intermediarios metabólicos en tejidos post-mitóticos y iii) plasma de especies más longevas; iv) la regulación del contenido de distintos elementos específicos del complejo 1 de mTOR en términos de longevidad; y v) la existencia de un perfil metabólico asociado a humanos de longevidad extrema.
Los resultados obtenidos muestran la existencia de perfiles metabólicos asociados a la longevidad de las especies que, en algunos casos, son diferentes a aquellos perfiles asociados a la longevidad individual. Además, las especies más longevas han evolucionado disminuyendo el contenido de determinadas subunidades del complejo I que podrían ser responsables de la menor producción de especies reactivas de oxígeno. Por otra parte, existen factores genéticos que podrían determinar la actividad basal de mTOR, y que podrían, al menos en parte, explicar el fenotipo asociado a la longevidad. Por lo tanto, parece que lograr una mayor longevidad implica una adaptación metabólica y estructural.<br>Long-lived species have evolved by decreasing the rate of endogenous reactive oxygen species production and providing them of oxidation-resistant structures. Hence, species that live longer benefit from metabolically efficient and structurally stable mitochondria. In fact, phenotypic traits of longevity include reduced content of complex I and sulphur-containing amino acids. Then, the activity of selected intracellular signalling pathways plays a key role regulating the expression of genes associated to a longevity phenotype.
In this context, this thesis aims to determine i) the modulation of specific complex I subunits associated to longevity; ii) the changes on sulphur amino acids content and its metabolic intermediates in post-mitotic tissues and ii) plasma from long-lived species; iv) the content regulation of the different mTOR complex 1 specific forming elements in terms of longevity; and v) the existence of a metabolic profile associated to human extreme longevity.
The obtained results reveal the existence of metabolic profiles associated to species longevity that, in some cases, differ from those profile associated to individual longevity. Furthermore, longer lived species have evolved reducing the content of specific complex 1 subunits that might be responsible for the limited reactive oxygen species production. Otherwise, genetic factors that might determine the basal activity of mTORC1 exist, and that could, at least In part, explain the longevity associated phenotype. Thus, it seems that the achievement of an extended longevity implies a metabolic and structural adaptation.
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Howbrook, David. "Development of an oxidative stress-responsive biosensor." Thesis, University of Surrey, 2000. http://epubs.surrey.ac.uk/844280/.
Повний текст джерелаАнотація:
The promoter region of the katG gene of Escherichia coli has been fused to two reporter genes GFPuv, encoding green fluorescent protein derived from Aequorea victoria and luxCDABE, encoding bacterial luciferase, from Photorhadbus luminescens to compare the qualities of these two reporters in microbial biosensor applications. In Escherichia coli both reporter systems produce stable signals. The lux construct was more sensitive at lower concentrations of hydrogen peroxide and the response time was shorter when compared with GFPuv. The latter, however, was better able to sense oxidative stress at concentrations that impaired signal output in the E. coli lux system. Low level non-induced bioluminescence was observed using the P. luminescens reporter system and this was utilised to measure EC50. As many compounds produce an increase in luminescence when incubated with this system, there is no means of specifically identifying any oxidative pollutants in the unknown sample. The system is limited to compounds that produce oxidative stress. Here we describe a system to add specificity to the stress-response whole-cell biosensor using glucose oxidase, which produces from glucose, hydrogen peroxide and gluconate. On incubation of these two adjuncts, glucose and glucose oxidase, with the pkatGlux whole cell biosensor, we found that the system was specific for glucose and had a range of sensitivity from 2 to 12 mM glucose. We propose that by adding glucose oxidase to the oxidative stress whole cell biosensor the specificity of the oxidative stress response can be increased, and by adding other oxidase enzymes the range of compounds that can be detected is expanded. There are enzymes of which the products of metabolism include glucose, beta-galactosidase converts lactose into glucose and galactose. The enzymes, beta-amylase and beta-amlyglucosidase digest starch to produce glucose and cellulases that act on cellulose to liberate glucose. Glucose oxidase then converts glucose to hydrogen peroxide and gluconate, the latter of which induces an increase in luminescence from the E. coli lux system. Thus it is possible to further develop the theme of adding in specificity to the stress response whole cell biosensor in the use of dual enzyme systems, where the first enzyme acts on the first substrate to yield glucose on to which glucose oxidase can metabolise, to yield hydrogen peroxide. If pkatGlux is incubated with a dual enzyme system then the number of compounds that can be biosensed can be increased and a greater specificity introduced. Samples may originate from lake, river or soil samples. These will not be 'clean'; they may contain organic debris, dirt and other bacteria that could interfere with the biosensing process. To this end lake and soil samples were spiked with substrates to see if direct sensing is possible, without the need for sample preparation. It was indicated that biosensing could take place in samples that originated from an aqueous environment. Where there were high levels of soil present, luminescence signal was quenched, which was restored on extraction of the substrate with appropriate solvent.
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Babintseva, A. G. "Oxidative Stress and Neonatal Acute Kidney Injury." Thesis, БДМУ, 2022. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/19793.
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SENFT, ALBERT PAUL. "AROMATIC HYDROCARBON RECEPTOR-DEPENDENT MITOCHONDRIAL OXIDATIVE STRESS." University of Cincinnati / OhioLINK, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1016461170.
Повний текст джерела