Academic literature on the topic 'GTP Homeostasis'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'GTP Homeostasis.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Journal articles on the topic "GTP Homeostasis"
1
Shen, Chwan-Li, Jannette M. Dufour, Jonathan M. Miranda, Gurvinder Kaur, Eunhee Chung, Latha Ramalingam, Naima Moustaid-Moussa, and Jay J. Cao. "Effect of Dietary Geranylgeraniol and Green Tea Polyphenols on Glucose Homeostasis, Bone Turnover Biomarkers, and Bone Microstructure in Obese Mice." International Journal of Molecular Sciences 24, no. 2 (January 4, 2023): 979. http://dx.doi.org/10.3390/ijms24020979.
Full textAbstract:
Previously, we demonstrated that the administration of either geranylgeraniol (GGOH) or green tea polyphenols (GTP) improved bone health. This study examined the combined effects of GGOH and GTP on glucose homeostasis in addition to bone remodeling in obese mice. We hypothesized that GGOH and GTP would have an additive or synergistic effect on improving glucose homeostasis and bone remodeling possibly in part via suppression of proinflammatory cytokines. Forty-eight male C57BL/6J mice were assigned to a high-fat diet (control), HFD + 400 mg GGOH/kg diet (GG), HFD + 0.5% GTP water (TP), or HFD + GGOH + GTP (GGTP) diet for 14 weeks. Results demonstrated that GTP supplementation improved glucose tolerance in obese mice. Neither GGOH nor GTP affected pancreas insulin or bone formation procollagen type I intact N-terminal, bone volume at the lumbar vertebrae, or bone parameters at the trabecular bone and cortical bone of the femur. There was an interactive effect for serum bone resorption collagen type 1 cross-linked C-telopeptide concentrations, resulting in no-GGOH and no-GTP groups having the highest values. GGOH increased trabecular number and decreased trabecular separation at the lumbar vertebrae. GTP increased trabecular thickness at lumbar vertebrae. The GG group produced the greatest connectivity density and the lowest structure model index. Only GTP, not GGOH, decreased adipokines concentrations (resistin, leptin, monocyte chemoattractant protein-1, and interleukin-6). In an obese male mouse model, individual GGOH and GTP supplementation improved glucose homeostasis, serum CTX, and trabecular microstructure of LV-4. However, the combined GGOH and GTP supplementation compromises such osteoprotective effects on serum CTX and trabecular bone of obese mice.
2
Seccia, Roberta, Silvia De Santis, Maria A. Di Noia, Ferdinando Palmieri, Daniela V. Miniero, Raffaele Marmo, Eleonora Paradies, et al. "Citrate Regulates the Saccharomyces cerevisiae Mitochondrial GDP/GTP Carrier (Ggc1p) by Triggering Unidirectional Transport of GTP." Journal of Fungi 8, no. 8 (July 29, 2022): 795. http://dx.doi.org/10.3390/jof8080795.
Full textAbstract:
The yeast mitochondrial transport of GTP and GDP is mediated by Ggc1p, a member of the mitochondrial carrier family. The physiological role of Ggc1p in S. cerevisiae is probably to transport GTP into mitochondria in exchange for GDP generated in the matrix. ggc1Δ cells exhibit lower levels of GTP and increased levels of GDP in mitochondria, are unable to grow on nonfermentable substrates and lose mtDNA. Because in yeast, succinyl-CoA ligase produces ATP instead of GTP, and the mitochondrial nucleoside diphosphate kinase is localized in the intermembrane space, Ggc1p is the only supplier of mitochondrial GTP required for the maturation of proteins containing Fe-S clusters, such as aconitase [4Fe-4S] and ferredoxin [2Fe-2S]. In this work, it was demonstrated that citrate is a regulator of purified and reconstituted Ggc1p by trans-activating unidirectional transport of GTP across the proteoliposomal membrane. It was also shown that the binding site of Ggc1p for citrate is different from the binding site for the substrate GTP. It is proposed that the citrate-induced GTP uniport (CIGU) mediated by Ggc1p is involved in the homeostasis of the guanine nucleotide pool in the mitochondrial matrix.
3
Rodríguez-Fdez, Sonia, and Xosé R. Bustelo. "Rho GTPases in Skeletal Muscle Development and Homeostasis." Cells 10, no. 11 (November 2, 2021): 2984. http://dx.doi.org/10.3390/cells10112984.
Full textAbstract:
Rho guanosine triphosphate hydrolases (GTPases) are molecular switches that cycle between an inactive guanosine diphosphate (GDP)-bound and an active guanosine triphosphate (GTP)-bound state during signal transduction. As such, they regulate a wide range of both cellular and physiological processes. In this review, we will summarize recent work on the role of Rho GTPase-regulated pathways in skeletal muscle development, regeneration, tissue mass homeostatic balance, and metabolism. In addition, we will present current evidence that links the dysregulation of these GTPases with diseases caused by skeletal muscle dysfunction. Overall, this information underscores the critical role of a number of members of the Rho GTPase subfamily in muscle development and the overall metabolic balance of mammalian species.
4
Khadilkar, Rohan J., Diana Rodrigues, Ridim Dadasaheb Mote, Arghyashree Roychowdhury Sinha, Vani Kulkarni, Srivathsa Subramanya Magadi, and Maneesha S. Inamdar. "ARF1–GTP regulates Asrij to provide endocytic control ofDrosophilablood cell homeostasis." Proceedings of the National Academy of Sciences 111, no. 13 (March 18, 2014): 4898–903. http://dx.doi.org/10.1073/pnas.1303559111.
Full text
5
Mazhab-Jafari, Mohammad T., Christopher B. Marshall, Noboru Ishiyama, Jason Ho, Vanessa Di Palma, Vuk Stambolic, and Mitsuhiko Ikura. "An Autoinhibited Noncanonical Mechanism of GTP Hydrolysis by Rheb Maintains mTORC1 Homeostasis." Structure 20, no. 9 (September 2012): 1528–39. http://dx.doi.org/10.1016/j.str.2012.06.013.
Full text
6
Chen, Hui-Jie, Na Li, Ye Luo, Yong-Liang Jiang, Cong-Zhao Zhou, Yuxing Chen, and Qiong Li. "The GDP-switched GAF domain of DcpA modulates the concerted synthesis/hydrolysis of c-di-GMP in Mycobacterium smegmatis." Biochemical Journal 475, no. 7 (April 9, 2018): 1295–308. http://dx.doi.org/10.1042/bcj20180079.
Full textAbstract:
The second messenger c-di-GMP [bis-(3′-5′)-cyclic dimeric guanosine monophosphate] plays a key role in bacterial growth, survival and pathogenesis, and thus its intracellular homeostasis should be finely maintained. Mycobacterium smegmatis encodes a GAF (mammalian cGMP-regulated phosphodiesterases, Anabaenaadenylyl cyclases and Escherichia coli transcription activator FhlA) domain containing bifunctional enzyme DcpA (diguanylate cyclase and phosphodiesterase A) that catalyzes the synthesis and hydrolysis of c-di-GMP. Here, we found that M. smegmatis DcpA catalyzes the hydrolysis of c-di-GMP at a higher velocity, compared with synthetic activity, resulting in a sum reaction from the ultimate substrate GTP to the final product pGpG [5′-phosphoguanylyl-(3′-5′)-guanosine]. Fusion with the N-terminal GAF domain enables the GGDEF (Gly-Gly-Asp-Glu-Phe) domain of DcpA to dimerize and accordingly gain synthetic activity. Screening of putative metabolites revealed that GDP is the ligand of the GAF domain. Binding of GDP to the GAF domain down-regulates synthetic activity, but up-regulates hydrolytic activity, which, in consequence, might enable a timely response to the transient accumulation of c-di-GMP at the stationary phase or under stresses. Combined with the crystal structure of the EAL (Glu-Ala-Leu) domain and the small-angle X-ray scattering data, we propose a putative regulatory model of the GAF domain finely tuned by the intracellular GTP/GDP ratio. These findings help us to better understand the concerted control of the synthesis and hydrolysis of c-di-GMP in M. smegmatis in various microenvironments.
7
Kristensson, Maria Alvarado. "The Game of Tubulins." Cells 10, no. 4 (March 28, 2021): 745. http://dx.doi.org/10.3390/cells10040745.
Full textAbstract:
Members of the tubulin superfamily are GTPases; the activities of GTPases are necessary for life. The members of the tubulin superfamily are the constituents of the microtubules and the γ-tubulin meshwork. Mutations in members of the tubulin superfamily are involved in developmental brain disorders, and tubulin activities are the target for various chemotherapies. The intricate functions (game) of tubulins depend on the activities of the GTP-binding domain of α-, β-, and γ-tubulin. This review compares the GTP-binding domains of γ-tubulin, α-tubulin, and β-tubulin and, based on their similarities, recapitulates the known functions and the impact of the γ-tubulin GTP-binding domain in the regulation of the γ-tubulin meshwork and cellular homeostasis.
8
Kotelevets, Larissa, and Eric Chastre. "Rac1 Signaling: From Intestinal Homeostasis to Colorectal Cancer Metastasis." Cancers 12, no. 3 (March 12, 2020): 665. http://dx.doi.org/10.3390/cancers12030665.
Full textAbstract:
The small GTPase Rac1 has been implicated in a variety of dynamic cell biological processes, including cell proliferation, cell survival, cell-cell contacts, epithelial mesenchymal transition (EMT), cell motility, and invasiveness. These processes are orchestrated through the fine tuning of Rac1 activity by upstream cell surface receptors and effectors that regulate the cycling Rac1-GDP (off state)/Rac1-GTP (on state), but also through the tuning of Rac1 accumulation, activity, and subcellular localization by post translational modifications or recruitment into molecular scaffolds. Another level of regulation involves Rac1 transcripts stability and splicing. Downstream, Rac1 initiates a series of signaling networks, including regulatory complex of actin cytoskeleton remodeling, activation of protein kinases (PAKs, MAPKs) and transcription factors (NFkB, Wnt/β-catenin/TCF, STAT3, Snail), production of reactive oxygen species (NADPH oxidase holoenzymes, mitochondrial ROS). Thus, this GTPase, its regulators, and effector systems might be involved at different steps of the neoplastic progression from dysplasia to the metastatic cascade. After briefly placing Rac1 and its effector systems in the more general context of intestinal homeostasis and in wound healing after intestinal injury, the present review mainly focuses on the several levels of Rac1 signaling pathway dysregulation in colorectal carcinogenesis, their biological significance, and their clinical impact.
9
Gumataotao, Natalie, K. P. Wasantha Lankathilaka, Brian Bennett, and Richard C. Holz. "The iron-type nitrile hydratase activator protein is a GTPase." Biochemical Journal 474, no. 2 (January 6, 2017): 247–58. http://dx.doi.org/10.1042/bcj20160884.
Full textAbstract:
The Fe-type nitrile hydratase activator protein from Rhodococcus equi TG328-2 (ReNHase TG328-2) was successfully expressed and purified. Sequence analysis and homology modeling suggest that it is a G3E P-loop guanosine triphosphatase (GTPase) within the COG0523 subfamily. Kinetic studies revealed that the Fe-type activator protein is capable of hydrolyzing GTP to GDP with a kcat value of 1.2 × 10−3 s−1 and a Km value of 40 μM in the presence of 5 mM MgCl2 in 50 mM 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid at a pH of 8.0. The addition of divalent metal ions, such as Co(II), which binds to the ReNHase TG328-2 activator protein with a Kd of 2.9 μM, accelerated the rate of GTP hydrolysis, suggesting that GTP hydrolysis is potentially connected to the proposed metal chaperone function of the ReNHase TG328-2 activator protein. Circular dichroism data reveal a significant conformational change upon the addition of GTP, which may be linked to the interconnectivity of the cofactor binding sites, resulting in an activator protein that can be recognized and can bind to the NHase α-subunit. A combination of these data establishes, for the first time, that the ReNHase TG328-2 activator protein falls into the COG0523 subfamily of G3E P-loop GTPases, many of which play a role in metal homeostasis processes.
10
Mori, Risa, and Takashi Toda. "The dual role of fission yeast Tbc1/cofactor C orchestrates microtubule homeostasis in tubulin folding and acts as a GAP for GTPase Alp41/Arl2." Molecular Biology of the Cell 24, no. 11 (June 2013): 1713–24. http://dx.doi.org/10.1091/mbc.e12-11-0792.
Full textAbstract:
Supplying the appropriate amount of correctly folded α/β-tubulin heterodimers is critical for microtubule dynamics. Formation of assembly-competent heterodimers is remarkably elaborate at the molecular level, in which the α- and β-tubulins are separately processed in a chaperone-dependent manner. This sequential step is performed by the tubulin-folding cofactor pathway, comprising a specific set of regulatory proteins: cofactors A–E. We identified the fission yeast cofactor: the orthologue of cofactor C, Tbc1. In addition to its roles in tubulin folding, Tbc1 acts as a GAP in regulating Alp41/Arl2, a highly conserved small GTPase. Of interest, the expression of GDP- or GTP-bound Alp41 showed the identical microtubule loss phenotype, suggesting that continuous cycling between these forms is important for its functions. In addition, we found that Alp41 interacts with Alp1D, the orthologue of cofactor D, specifically when in the GDP-bound form. Intriguingly, Alp1D colocalizes with microtubules when in excess, eventually leading to depolymerization, which is sequestered by co-overproducing GDP-bound Alp41. We present a model of the final stages of the tubulin cofactor pathway that includes a dual role for both Tbc1 and Alp1D in opposing regulation of the microtubule.
Dissertations / Theses on the topic "GTP Homeostasis"
1
Zolle, Lapuente Olga C. "Cyclic GMP and calcium homeostasis in endothelial cells." Thesis, University of Liverpool, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.367654.
Full text
2
Abrahamsson, Niclas. "On the Impact of Bariatric Surgery on Glucose Homeostasis." Doctoral thesis, Uppsala universitet, Institutionen för medicinska vetenskaper, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-276381.
Full textAbstract:
Obesity has grown to epidemic proportions, and in lack of efficient life-style and medical treatments, the bariatric surgeries are performed in rising numbers. The most common surgery is the Gastric Bypass (GBP) surgery, with the Biliopancreatic diversion with duodenal switch (DS) as an option for the most extreme cases with a BMI>50 kg/m2. In paper I 20 GBP-patients were examined during the first post-operative year regarding the natriuretic peptide, NT-ProBNP, which is secreted from the cardiac ventricles. Levels of NT-ProBNP quickly increased during the first post-surgery week, and later established itself on a higher level than pre-surgery. In paper II we report of 5 patient-cases after GBP-surgery with severe problems with postprandial hypoglycaemia that were successfully treated with GLP-1-analogs. The effect of treatment could be observed both symptomatically and in some cases using continuous glucose measuring systems (CGMS). In paper III three groups of subjects; 15 post-GBP patients, 15 post-DS, and 15 obese controls were examined for three days using CGMS during everyday life. The post-GBP group had high glucose variability as measured by MAGE and CONGA, whereas the post-DS group had low variability. Both post-operative groups exhibited significant time in hypoglycaemia, about 40 and 80 minutes per day <3.3mmol/l and 20 and 40 minutes < 2.8mmol/l, respectively, longer time for DS-group. Remarkably, only about 20% of these hypoglycaemic episodes were accompanied with symptoms. In Paper IV the hypoglycaemia counter regulatory system was investigated; 12 patients were examined before and after GBP-surgery with a stepped hypoglycaemic hyperinsulinemic clamp. The results show a downregulation of symptoms, counter regulatory hormones (glucagon, cortisol, epinephrine, norepinephrine, growth hormone), incretin hormones (GLP-1 and GIP), and sympathetic nervous response. In conclusion patients post bariatric surgery exhibit a downregulated counter regulatory response to hypoglycaemia, accompanied by frequent asymptomatic hypoglycaemic episodes in everyday life. Patients suffering from severe hypoglycaemic episodes can often be treated successfully with GLP-1-analogues.
3
Lusche, Daniel Felix. "Cyclic GMP in the development of the social amoeba Dictyostelium discoideum regulation of calcium homeostasis by cGMP. /." [S.l. : s.n.], 2004. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB11482073.
Full text
4
Schmitt, Charlotte. "Implication du transporteur intestinal GLUT2 dans l'absorption des sucres et la fonction entéroendocrine." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066465.
Full textAbstract:
L'épithélium intestinal, en constant renouvellement, assure de nombreuses fonctions vitales comme l'absorption des nutriments et le maintien d'une barrière entre le milieu extérieur et l'organisme. L'absorption intestinale des sucres est assurée par de nombreux transporteurs au niveau de l'intestin proximal. Parmi eux, GLUT2, localisé dans les entérocytes et les cellules endocrines de l'intestin, transporte le glucose, le fructose et le galactose. Les cellules L entéroendocrines produisent le GLP-1, un puissant stimulateur de la sécrétion d'insuline en réponse au glucose. L'objectif de ma thèse a été d'élucider le rôle de GLUT2 intestinal dans l'absorption des sucres et la fonction entéroendocrine grâce à l'étude d'un modèle murin spécifiquement invalidé pour ce transporteur dans les cellules épithéliales intestinales. La délétion intestinale de GLUT2 entraîne une malabsorption intestinale modérée des sucres associée à une distribution retardée du glucose aux tissus périphériques. Le retard spatial et temporel de l'absorption des sucres provoque une dysbiose intestinale au profit de bactéries ayant un rôle protecteur de l'homéostasie intestinale. De façon surprenante, l'invalidation de GLUT2 intestinal s'accompagne d'une chute de la densité de cellules L entéroendocrines, sans modification des niveaux plasmatiques de GLP-1. Cette étude met en exergue le rôle primordial de GLUT2 intestinal dans l'absorption des sucres et la fonction endocrine de l'intestin. Elle permet d'envisager le criblage de molécules capables d'inhiber l'activité de GLUT2 intestinal, pour atténuer la prise de poids et limiter les perturbations métaboliques induites par des régimes riches en sucresThe constantly renewing intestinal epithelium handles various essential functions including nutrient absorption and persistence of a barrier between our internal and external environments. Several transporters mediate sugar absorption in the proximal intestine. Among them, GLUT2, a very efficient glucose, fructose and galactose transporter and receptor, is located at the membranes of enterocytes and enteroendocrine cells. The enteroendocrine L-cells produce GLP-1, a strong activator of glucose-induced insulin secretion. This thesis aimed to further decipher the role of intestinal GLUT2 in sugar absorption and enteroendocrine cell function. To address this question, mice lacking GLUT2 specifically in intestinal epithelial cells have been generated and studied. Intestinal GLUT2 invalidation alters intestinal glucose absorption and delays glucose biodistribution to peripheral tissues. This spatial and temporal sugar absorption delay provokes intestinal dysbiosis, favoring gut microbiota having a protective impact on gut homeostasis. Surprisingly, intestinal GLUT2 deletion leads to a strong loss in enteroendocrine L cell density, with no impact on GLP-1 plasma levels. This study highlights critical roles for GLUT2 in sugar absorption and enteroendocrine cell function management. The use of specific GLUT2 inhibitors could be considered to limit body weight gain and metabolic disorders induced by sugar rich diets
5
Berbel, Luciane Celeste Lazari. "Influência da variação genotípica Glu354Gln do receptor para o GIP sobre a homeostase glicêmica e a sensibilidade insulínica em indivíduos sadios." Universidade Estadual de Londrina. Centro de Ciências da Saúde. Programa de Pós-Graduação em Ciências da Saúde, 2014. http://www.bibliotecadigital.uel.br/document/?code=vtls000189459.
Full textAbstract:
A possível variabilidade na resposta fisiológica hormonal após a alimentação, relacionada à elevação do GIP pós-prandial entre indivíduos, despertou o interesse para avaliar a influência do polimorfismo no gene para o receptor do polipeptídeo insulinotrópico dependente de glicose (GIPR) na homeostase glicêmica e na função da célula beta pancreática. Foram estudados 25 adultos (12 mulheres, 13 homens) com IMC<30 e sem doenças relacionadas à síndrome metabólica. Foram coletadas amostras de sangue nos tempos basal (T0) e após refeição contendo 58g de carboidratos e 28g de lipídeos a cada 30 minutos até o T150, para dosagem de insulinemia e glicemia. Foi realizada pesquisa da variante Glu354Gln para o GIPR (SNPGIPR, rs1800437) em amostra de sangue periférico pela técnica de PCRRFLP. Foi avaliada a homeostase glicêmica de jejum e pós-prandial através dos cálculos de HOMA-IR, HOMA-B, área sob a curva (AUC) de insulina e glicemia e sua razão (AUCi/AUCg), índice insulinogênico (IGI) em cada tempo relativo ao basal e razão IGI/HOMA-IR. Na curva pós-prandial, 72% dos indivíduos apresentaram picos de glicose e 64% de insulina até o T60, com média de 107 mg/dl e 42,1 UI/mL, respectivamente. A pesquisa do SNP-GIPR revelou alelo C presente (C+, polimórfico) em 7 indivíduos, com 72% dos genótipos GG, 24% GC e 4% CC. Houve diferença significativa entre C+ e o grupo com alelo C ausente (C-) em relação ao HOMA-B (100+/-26 vs 160+/- 189%, respectivamente; p=0,04). Não houve diferença estatisticamente significativa quanto aos seguintes parâmetros: AUCg, AUCi, HOMA-IR, IGI e razões AUCi/AUCg e IGI/HOMA-IR. Porém, em todos os tempos, o IGI foi superior no grupo C+ (T30, 189%; T60, 147%; T90, 1066%; T120, 29% e T150, 93%), enquanto que uma tendência semelhante ocorreu para a razão IGI/HOMA-IR exceto no T150. O indivíduo portador do SNP-GIPR em homozigose (CC) apresentou resposta precoce de insulina. Além disso, 42,9% dos indivíduos C+ apresentaram história familiar de diabetes em comparação com 22,2% do grupo C- (p=0,29). Em conclusão, estudamos o perfil de glicemia e insulina de jejum e na curva pós-prandial incluindo 1ª e 2ª fases de secreção insulínica de uma amostra de indivíduos sadios com distribuição genotípica do SNP-GIPR semelhante à população reportada na literatura. Indivíduos euglicêmicos C+ e C- apresentaram semelhanças em diversos dos parâmetros utilizados para avaliar a função da célula beta pancreática e resistência insulínica. Por outro lado, foi encontrada variação no HOMA-B entre os genótipos estudados, sugerindo redução na função da célula beta relacionada ao polimorfismo do GIPR, sem alteração na sensibilidade à insulina. A redução do HOMA-B em indivíduos sadios, independente do histórico familiar de diabetes, sugere aprofundar o estudo deste SNP-GIPR como possível marcador precoce para o risco de falência pancreática associada ao diabetes tipo 2.The potential variability in hormonal physiological response after feeding, related to the elevation of postprandial GIP between individuals, arouse interest to evaluate the influence of polymorphisms in the gene for glucose-dependent insulinotropic polypeptide receptor (GIPR) in glucose homeostasis and in pancreatic beta cell function. Altogether 25 adults (12 women, 13 men) with BMI <30 and without metabolic syndrome related diseases were studied. After diet containing 58g of carbohydrates and 28g of lipids, blood samples at baseline (T0) and every 30 minutes until the T150 were collected for measurement of insulin and glucose. The polymorphic GIPR variant Glu354Gln, rs1800437 (SNP-GIPR) was studied in peripheral blood sample through PCR-RFLP. Glucose homeostasis in fasting and postprandial was assessed by calculating HOMA-IR, HOMA-B, area under the curve (AUC) of insulin and glucose, AUCi/AUCg ratio, insulinogenic index (IGI) at each time relative to baseline and IGI/HOMA-IR ratio. In the postprandial curve, 72% of subjects showed glucose peaks and 64% insulin until the T60, with mean of 107 mg/dl and 42.1 IU/mL, respectively. The SNP-GIPR study revealed presence of C allele (C+) in 7 individuals, with 72% of the genotypes GG, 24% GC and 4%CC. There was a significant difference between C + or the group without C allele (C-) in HOMA-B (100 +/- 26 vs. 160 +/- 89 % respectively; p = 0.04).There was no significant difference in the following parameters: AUCg, AUCi, HOMA-IR, IGI, AUCi/AUCg and IGI/HOMA-IR. However, the IGI was higher in the C+ allele group at all time-points (T30, 189%; T60, 147%; T90, 1066%; T120, 29% and T150, 93%), while a similar trend occurred for the IGI/HOMA-R ratio, except in T150. Furthermore, family history of diabetes was positive in 42.9% of C+ subjects, compared with 22.2% from C- group (p = 0.29). In conclusion, we have studied the fasting and postprandial variation of glucose and insulin, including insulin secretions 1st and 2nd phases of healthy subjects; our sample presented genotype distribution similar to the reported population in the literature. C+ and C- euglycemic subjects had similar parameters of beta cell function and insulin sensitivity. In other way, we found variation in HOMA-B according to the genotype, suggesting a reduction in beta cell function related to GIPR polymorphism, without change in insulin sensitivity. The reduction in HOMA-B in healthy individuals, regardless of family history of diabetes, suggests further study of this SNP-GIPR as a possible early marker for the risk of pancreatic failure associated with type 2 diabetes.
6
Ayari, Sami. "Implication des récepteurs nucléaires HNF-4α et HNF-4γ dans la fonction entéroendocrine et la susceptibilité à l'obésité et au diabète de type II." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066380.
Full textAbstract:
L’obésité et le diabète de type 2 (DT2) sont des pathologies métaboliques associées à des perturbations de l’homéostasie glucidique et énergétique. Les enterohormones sont des acteurs importants de la regulation des mécanismes perturbés lors de ces pathologies. Parmi ces enterohormones, le GLP-1, sécrété par les cellules entéroendocrines de type L suite à un repas, permet d’amplifier la sécrétion d’insuline par les cellules β-pancréatiques et de diminuer la prise alimentaire. L’objectif de ma thèse a été de caractériser le rôle du récepteur nucléaire HNF-4γ dans l’homéostasie énergétique et la fonction endocrine de l’intestin.A l’aide d’un modèle murin d’invalidation totale et constitutive du facteur de transcription HNF-4γ, notre équipe a mis en évidence que l’absence de HNF-4γ induit une amélioration de la tolérance au glucose grâce à une augmentation du nombre de cellules L et de la quantité plasmatique de GLP-1 en réponse au glucose. L’ensemble de ces données démontre pour la première fois un rôle de HNF-4γ dans l’homéostasie glucidique via une modulation du lignage enteroendocrine spécifique du GLP-1 et suggère que son absence pourrait protéger les souris de l’établissement d’un DT2.Par ailleurs, la perte d’expression de HNF-4γ confère une protection vis-à-vis de la prise de poids et de l’intolérance au glucose normalement induites par six semaines d’un régime riche en lipides et en fructose grâce une perte énergétique accrue dans les fécès essentiellement due à une malabsorption des acides gras.En conclusion, cette étude met en exergue le rôle du récepteur nucléaire intestinal HNF-4γ dans la fonction enteroendocrine et la susceptibilité à l’obésité et au DT2Obesity and type 2 diabetes (T2D) are metabolic pathologies associated with glucose and energy homeostasis perturbations. Enterohormones are important players in the regulation of the mechanisms disturbed during these pathologies. Among these enterohormones, GLP-1, secreted by enteroendocrine L cells in response to a meal, potentiates insulin secretion by pancreatic β cells and inhibits food intake. The aim of my thesis was to characterize the role of the nuclear receptor HNF-4γ in the energy homeostasis and the endocrine function of the intestine.By using a total and constitutive HNF-4γ knock-out mouse model, our team has highlighted that the loss of hnf-4γ induces an improved glucose tolerance. This effect is due to an increased GLP-1 cell number and GLP-1 plasma levels in response to glucose. All together these data demonstrate for the first time a role of HNF-4γ in glucose homeostasis through a modulation of the enteroendocrine lineage specific for GLP-1 and suggest that its absence could protect mice from the T2D establishment.The loss of HNF-4γ protects mice from body weight gain and glucose intolerance normally induced by six weeks of a high-fat/high-fructose diet demonstrating its involvement in obesity and T2D. HNF-4γ -/- mice are protected from obesity by a greater energy loss in faeces mainly due to lipid malabsorption. These results demonstrate that HNF-4γ is necessary for the intestinal fatty acids uptake.In conclusion, this study highlights the role of the intestinal nuclear receptor HNF-4γ in enteroendocrine function and susceptibility to obesity and T2D
7
Domingues, Ana Sofia Jesus. "A reporter system to study the role of tRNA modifying enzymes in human proteostasis." Master's thesis, Universidade de Aveiro, 2016. http://hdl.handle.net/10773/21083.
Full textAbstract:
Mestrado em Biologia Molecular e CelularA síntese proteica é um processo essencial para que todos os organismos mantenham a homeostasia celular. Os tRNAs são elementos cruciais na síntese proteica, uma vez que codificam a informação genética presente no mRNA. A linha celular HeLa, utilizada neste estudo, foi primeiramente isolada de uma mulher com cancro do colo do útero e desde então tem sido bastante usada na investigação, sendo muito importante no estudo das bases moleculares de muitas doenças. De modo a monitorizar a agregação proteica nesta linha celular, um sistema repórter foi desenvolvido utilizando uma fusão entre HspB1 (Hsp27) e a GFP. HspB1 é um chaperone molecular com capacidade de recrutar outros chaperones e restabelecer a conformação ideal das proteínas em situações de stress. A GFP é uma proteína fluorescente que marca certas condições biológicas de interesse. Para perceber o impacto dos erros da tradução na agregação de proteínas e no surgimento das doenças, o principal objetivo deste estudo foi desenvolver uma linha celular estável (HeLa) expressando um sistema repórter HspB1-GFP, de modo a monitorizar os erros no enovelamento das proteínas em resposta ao stress proteotóxico. Ao longo deste estudo o sistema repórter expressando HspB1-GFP foi desenvolvido com sucesso, permitindo assim a sua utilização para identificar situações fisiológicas e patológicas em que a agregação de proteínas ocorre em células de mamífero.
Protein synthesis is essential for all organisms to maintain cell homeostasis. tRNAs are crucial elements in protein synthesis as they decode the genetic information organized in the mRNA codons. A HeLa cell line, used in this study, was first isolated from a woman with cervical cancer and since then was highly used in biological studies, being extremely important in the study of the molecular basis of several diseases. In order to monitor protein aggregation in this cell line, a reporter system was developed using an HspB1 (Hsp27) and a GFP fusion. HspB1 is a small heat shock protein that, in stress situations, recruits other proteins in order to restore the conformation of the proteins. GFP is a biosensor that reports several cellular conditions of interest. To understand the impact of translation errors on protein aggregation and on the disease arising, the main goal of this study was to develop a stable cell line (HeLa) expressing a reporter system HspB1-GFP to monitor the protein misfolding in response to proteotoxic stress. During this study, the reporter system expressing HspB1-GFP was developed successfully, allowing the identification of physiological and pathological situations where protein aggregation occurs in mammalian cells.
8
Gupta, Kuldeepkumar Ramnaresh. "(p)ppGpp and c-di-GMP : A Tale of Two Second Messengers in Mycobacterium smegmatis." Thesis, 2015. http://etd.iisc.ac.in/handle/2005/4117.
Full textAbstract:
Nucleotide based second messengers are known to regulate wide variety of processes in all domains of life. Two such bacterial second messengers are (p)ppGpp (guanosine tetra- or pentaphosphate) and c-di-GMP (cyclic dimeric guanosine monophosphate). The alarmone (p)ppGpp is synthesized by bacteria to face any kind of stress; while the signalling nucleotide c-di-GMP is synthesized principally to switch from motile (planktonic) to sessile (biofilm) life style. Apart from mediating the said functions, these nucleotides also regulate transcription, translation, replication, virulence and pathogenicity of the several bacterial species. In this work, we have tried to uncover novel functions or phenotypes that are governed by the second messengers (p)ppGpp and c-di-GMP in Mycobacterium smegmatis. In M. smegmatis, (p)ppGpp and c-di-GMP are synthesized and degraded by the bifunctional proteins RelMsm and DcpA, respectively. The architecture of both the proteins is similar; the synthesis and hydrolysis domains for the second messengers occur in tandem. The knockout mutants of relMsm and dcpA genes, ∆relMsm and ∆dcpA, have been used in this study to uncover the novel functions of these second messengers in mycobacterial physiology. Chapter 1 provides is an overview of the current literature pertaining to (p)ppGpp and c-di-GMP. An historical perspective with regard to the discovery of the (p)ppGpp and c-di-GMP is given. The metabolism of these second messengers has been discussed. This has been followed by the description of various functions governed by the second messengers. Finally, the scope of the current work has been outlined.
Chapter 2 investigates the effect of disrupting (p)ppGpp and c-di-GMP signalling on the antibiotic sensitivity in M. smegmatis. Using Phenotype Microarray (PM) technology, the growth of ∆relMsm and ∆dcpA knock out strains was compared to those of the wild-type and respective complemented strains in 240 different antimicrobials. It was found that the knockout mutants displayed enhanced survival in the presence of multiple antibiotics. The PM data was corroborated by the independent determination of minimum inhibitory concentrations of seven different antibiotics. Finally, the plausible reasons for the multidrug resistance of ∆relMsm and ∆dcpA strains have been discussed.
Chapter 3 explores how the impairment of (p)ppGpp and c-di-GMP alters the cell wall of M. smegmatis. Thin layer chromatography analysis of cell wall fractions such as glycopeptidolipids (GPLs), mycolic acids, polar and apolar lipids was carried out. It was found that the amount of GPLs and polar lipids were reduced in the ∆relMsm and ∆dcpA knockout strains.
Chapter 4 explores the effect of (p)ppGpp and c-di-GMP on the growth, cell morphology and cell division in M. smegmatis. It was found that the ∆relMsm and ∆dcpA knockout strains have slow growth compared to those of the wild type and respective complemented strain. The overproduction of (p)ppGpp and c-di-GMP, achieved through overexpression of Rel and DcpA proteins, encased the overexpression strains relOE and dcpAOE in a biofilm like matrix. The higher levels of (p)ppGpp and c-di-GMP caused M. smegmatis assume coccoid morphology. Microscopy analyses revealed that the ∆relMsm and ∆dcpA strains are elongated, multinucleate and multiseptate.
Chapter 5 explores effects of (p)ppGpp and c-di-GMP on the global gene expression profile in M. smegmatis. Many genes were shown to be differentially expressed in the ∆relMsm and ∆dcpA knockout strains. Genes regulating cell division, cell wall biosynthesis, superoxide metabolism or reactive oxygen species metabolism and genes encoding transporters were differentially expressed in the ∆relMsm and ∆dcpA knockout mutants. The microarray data were corroborated by quantitative real-time PCR. Gene expression data explained the multidrug resistance, the reduction in the level of GPLs and polar lipids, slow growth, changes in cell morphology and defective cell division exhibited by the ∆relMsm and ∆dcpA knockout mutants.
Chapter 6 summarizes the entire work embodied in the thesis.
Appendix 1 lists the 240 antimicrobials compounds and their mode of action for which antibiotic sensitivity of the ∆relMsm and ∆dcpA knockout mutants was tested.
Appendix 2 lists the growth differences among the knockout, wild type and complemented strains in the form of area under curve values.
Appendix 3 lists the genes that were differentially expressed in the ∆relMsm and ∆dcpA knockout strains.
Appendix 4 is a comprehensive review on the kinetic and thermodynamic parameters governing the sigma factor competition in Escherichia coli and how (p)ppGpp and anti-sigma factors regulate this competition among sigma factors for the limited pool of core RNA polymerase in E. coli.
9
Maida, Adriano. "Effects of Enteroendocrine Hormones on Beta-cell Function and Glucose Homeostasis." Thesis, 2011. http://hdl.handle.net/1807/29800.
Full textAbstract:
Mechanisms to augment the cellular function and mass of beta-cells may be effective means of treating type 2 diabetes. Important in the physiological control of beta-cell function and nutrient disposal are factors released from gut enteroendocrine cells during nutrient digestion. In enteroendocrine L-cells, post-translational processing of proglucagon gives rise to a number of proglucagon-derived peptides. One such peptide, glucagon-like peptide-1 (GLP-1), acts via its own receptor (GLP-1R) to stimulate beta-cell insulin secretion, proliferation and survival. Another, oxyntomodulin (OXM), weakly activates the GLP-1R and inhibits food intake in a GLP-1R-dependent manner in rodents, which led us to hypothesize that OXM modulates GLP-1R-dependent glucoregulation. While OXM did not mimic the inhibitory effect of GLP-1 on gastric emptying in mice, OXM stimulated insulin secretion, beta-cell survival and improved glucose tolerance in a GLP-1R-dependent manner.
In a similar manner to GLP-1, glucose-dependent insulinotropic polypeptide (GIP), secreted from enteroendocrine K-cells, physiologically stimulates insulin secretion via a distinct GIP receptor (GIPR) in beta-cells. Beyond the beta-cell, GIP and GLP-1 appear to exert divergent actions for the control of glucose homeostasis. Moreover, I illustrate that physiological and pharmacological GLP-1R signalling may be comparatively more important for the preservation of beta-cell mass and glucose homeostasis in murine streptozotocin-induced diabetes.
Lastly, studies in rodents and humans have showed that metformin increases circulating levels of GLP-1, leading us to hypothesize that GIP and GLP-1 may be involved in the glucoregulatory effects of metformin. Interestingly, transcripts for the Glp1r and Gipr were significantly increased within islets of metformin-treated mice, and metformin treatment enhanced the sensitivity of cultured beta-cells to GIP and GLP-1.
In summary, these studies illustrate mechanisms by which enteroendocrine peptides compare and contrast with respect to beta-cell survival and function and the control of glucose homeostasis.
10
Chiang, Yu-ting. "The Role of p21-activated Protein Kinase 1 in Metabolic Homeostasis." Thesis, 2014. http://hdl.handle.net/1807/44107.
Full textAbstract:
Our laboratory has demonstrated previously that the proglucagon gene (gcg), which encodes the incretin hormone GLP-1, is among the downstream targets of the Wnt signaling pathway; and that Pak1 mediates the stimulatory effect of insulin on Wnt target gene expression in mouse gut non- endocrine cells. Here, I asked whether Pak1 controls gut gcg expression and GLP-1 production, and whether Pak1 deletion leads to impaired metabolic homeostasis in mice. I detected the expression of Pak1 and two other group I Paks in the gut endocrine L cell line GLUTag, and co-localized Pak1 and GLP-1 in the mouse gut. Insulin was shown to stimulate Pak1 Thr423 and β-cat Ser675 phosphorylation. The stimulation of insulin on β-cat Ser675 phosphorylation, gcg promoter activity and gcg mRNA expression could be attenuated by the Pak inhibitor IPA3. Male Pak1-/- mice showed significant reduction in both gut and brain gcg expression levels, and attenuated elevation of plasma GLP-1 levels in response to oral glucose challenge. Notably, the Pak1-/- mice were intolerant to both intraperitoneal and oral glucose administration. Aged Pak1-/- mice showed a severe defect in response to intraperitoneal pyruvate challenge (IPPTT). In primary hepatocytes, however, IPA3 reduced basal glucose production, attenuated glucagon-stimulated glucose production, and inhibited the expression of Pck1 and G6pc. This implicates that the direct effect of group I Paks in hepatocytes is the stimulation of gluconeogenesis, and that the impairment in IPPTT in aged Pak1-/- mice is due to the lack of Pak1 elsewhere. The defect in IPPTT in aged Pak1-/- mice could be rescued by stimulating gcg expression with forskolin injection or by enhancing the incretin effect via sitagliptin administration. In summary, my study demonstrates that: 1) Pak1 positively regulates GLP-1 production, 2) Pak1/β-cat signaling plays a role in gut/liver axis or gut/pancreas/liver axis governing glucose homeostasis, and 3) Pak1-/- mice can be utilized as a novel model for metabolic research.
Books on the topic "GTP Homeostasis"
1
Hinder, Lucy M., Kelli A. Sullivan, Stacey A. Sakowski, and Eva L. Feldman. Mechanisms Contributing to the Development and Progression of Diabetic Polyneuropathy. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199937837.003.0114.
Full textAbstract:
Advances in our understanding of diabetes in human patients and experimental models indicate that a number of mechanisms may contribute to sensory nerve damage in diabetic polyneuropathy (DPN). In addition to oxidative stress, hyperglycemia and hyperlipidemia, recent research in pain, advanced glycation endproduct (AGE), and proteomics specify a contributory role for altered neuronal calcium homeostasis in DPN. Technology advances indicate neuronal energy balance and mitochondrial biogenesis, fission, and fusion are additional potential mechanisms. The effects of dysregulation or loss of insulin signaling and the effects of glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R) are also implicated.
2
Chakera, Aron, William G. Herrington, and Christopher A. O’Callaghan. Disorders of plasma potassium. Edited by Patrick Davey and David Sprigings. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199568741.003.0173.
Full textAbstract:
Potassium is the major intracellular cation, and maintenance of potassium homeostasis is critical for normal cellular function. Serum potassium levels usually range from 3.5–4.5 mmol/l (compared with intracellular levels of ~150 mmol/l). Hypokalaemia is defined as a serum potassium level <3.5 mmol/l, and hyperkalaemia as a serum potassium level >4.5 mmol/l. Hyperkalaemia occurs in over 5% of hospitalized patients, and is most common in older age groups, where it is associated with renal impairment and medication use. Medications that block the renin–angiotensin system, such as angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers, are often responsible. Hypokalaemia is also common, affecting over 15% of hospitalized patients, and is usually related to diuretic use, gastrointestinal losses, or inadequate potassium in the diet. This chapter reviews the causes and management of derangements of plasma potassium.
3
Nestler, Eric J. The Biological Basis of Depression. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190603342.003.0001.
Full textAbstract:
Most major advances in biomedical research have relied on the use of animal and cell models of disease. This is a particularly difficult challenge in psychiatry, because many core symptoms of mental illnesses are inherently inaccessible in animals. Moreover, because still today there are no bona fide molecular-cellular abnormalities that are pathogenomic for these illnesses, cell models are even more far afield. This chapter reviews efforts to overcome these obstacles and use animal and cell studies to better understand the biological basis of depression and to develop improved treatments. An important distinction is made between acute vs. chronic stress models as well as differentiating the changes that stress induces in brain that mediate deleterious maladaptations as opposed to homeostatic adaptations that help the individual cope with the stress. Studies along these lines are making major strides in identifying candidate molecular pathways that should be mined for new antidepressant treatments. However, a major gap in the field is the great difficulty in testing novel mechanisms in humans; closing this gap is one of the highest priorities for the field.
4
Joynt, Gavin M., and Gordon Y. S. Choi. Blood gas analysis in the critically ill. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0072.
Full textAbstract:
Arterial blood gases allow the assessment of patient oxygenation, ventilation, and acid-base status. Blood gas machines directly measure pH, and the partial pressures of carbon dioxide (PaCO2) and oxygen (PaO2) dissolved in arterial blood. Oxygenation is assessed by measuring PaO2 and arterial blood oxygen saturation (SaO2) in the context of the inspired oxygen and haemoglobin concentration, and the oxyhaemoglobin dissociation curve. Causes of arterial hypoxaemia may often be elucidated by determining the alveolar–arterial oxygen gradient. Ventilation is assessed by measuring the PaCO2 in the context of systemic acid-base balance. A rise in PaCO2 indicates alveolar hypoventilation, while a decrease indicates alveolar hyperventilation. Given the requirement to maintain a normal pH, functioning homeostatic mechanisms result in metabolic acidosis, triggering a compensatory hyperventilation, while metabolic alkalosis triggers a compensatory reduction in ventilation. Similarly, when primary alveolar hypoventilation generates a respiratory acidosis, it results in a compensatory increase in serum bicarbonate that is achieved in part by kidney bicarbonate retention. In the same way, respiratory alkalosis induces kidney bicarbonate loss. Acid-base assessment requires the integration of clinical findings and a systematic interpretation of arterial blood gas parameters. In clinical use, traditional acid-base interpretation rules based on the bicarbonate buffer system or standard base excess estimations and the interpretation of the anion gap, are substantially equivalent to the physicochemical method of Stewart, and are generally easier to use at the bedside. The Stewart method may have advantages in accurately explaining certain physiological and pathological acid base problems.
Book chapters on the topic "GTP Homeostasis"
1
Ransom, Bruce R. "Do Glial Gap Junctions Play a Role in Extracellular Ion Homeostasis?" In Neuroscience Intelligence Unit, 159–73. Berlin, Heidelberg: Springer Berlin Heidelberg, 1996. http://dx.doi.org/10.1007/978-3-662-21935-5_9.
Full text
2
Nadkarni, Prashant, Oleg G. Chepurny, and George G. Holz. "Regulation of Glucose Homeostasis by GLP-1." In Progress in Molecular Biology and Translational Science, 23–65. Elsevier, 2014. http://dx.doi.org/10.1016/b978-0-12-800101-1.00002-8.
Full text
3
Iorio, Jessica, Lisa Lastraioli, and Elena Lastraioli. "Potassium in Solid Cancers." In Physiology. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.101108.
Full textAbstract:
Electrolyte disorders are a frequent finding in cancer patients. In the majority of cases the etiologies of such disorders are common to all cancer types (i.e. diuretic-induced hyponatremia or hypokalemia). Sometimes, electrolyte disorders are caused by paraneoplastic syndromes or are due to cancer therapy. Potassium is one of the most important electrolytes of the human body since it is involved in the regulation of muscle contraction, maintenance of the integrity of the skeleton, blood pressure and nerve transmission as well as in the normal function of cells. Potassium homeostasis is strictly regulated since the gap between the recommended daily dietary intake (120 mEq/day) and the levels stored in the extracellular fluid (around 70 mEq) is huge. Alterations of potassium homeostasis are frequent in cancer patients as well alterations in potassium channels, the transmembrane proteins that mediate potassium fluxes within the cells. The present chapter is focused on the clinical significance of potassium homeostasis and potassium channels in patients with solid tumors.
4
Ventura, Raúl, and María Isabel Hernández-Alvarez. "Endoplasmic Reticulum: A Hub in Lipid Homeostasis." In Updates on Endoplasmic Reticulum [Working Title]. IntechOpen, 2022. http://dx.doi.org/10.5772/intechopen.105450.
Full textAbstract:
Endoplasmic Reticulum (ER) is the largest and one of the most complex cellular structures, indicating its widespread importance and variety of functions, including synthesis of membrane and secreted proteins, protein folding, calcium storage, and membrane lipid biogenesis. Moreover, the ER is implicated in cholesterol, plasmalogen, phospholipid, and sphingomyelin biosynthesis. Furthermore, the ER is in contact with most cellular organelles, such as mitochondria, peroxisomes, Golgi apparatus, lipid droplets, plasma membrane, etc. Peroxisomes are synthesized from a specific ER section, and they are related to very-long-chain fatty acid metabolism. Similarly, lipid droplets are vital structures in lipid homeostasis that are formed from the ER membrane. Additionally, there is a specific region between the ER-mitochondria interface called Mitochondria-Associated Membranes (MAMs). This small cytosolic gap plays a key role in several crucial mechanisms from autophagosome synthesis to phospholipid transfer. Due to the importance of the ER in a variety of biological processes, alterations in its functionality have relevant implications for multiple diseases. Nowadays, a plethora of pathologies like non-alcoholic steatohepatitis (NASH), cancer, and neurological alterations have been associated with ER malfunctions.
5
Rocha-Ortiz, Luis Roberto, Elva Leticia Perez-Luque, and Juan Manuel Malacara. "Analysis of Beta-Cell Function and GLP-1 Levels in Carriers of Rs7903146 and Rs12255372TCF7L2Genotypes in Mexican Pre-Diabetic Subjects." In BASIC/TRANSLATIONAL - Diabetes & Glucose Homeostasis: Genetic & Translational Approaches, P2–513—P2–513. The Endocrine Society, 2011. http://dx.doi.org/10.1210/endo-meetings.2011.part3.p6.p2-513.
Full text
6
Ponce, Arturo, Liora Shoshani, Alejandro Ogazon del Toro, and Marcelino Cereijido. "Influence of Cardiac Glycosides and Prostaglandins on the Physiology of Epithelial Cells." In Human Physiology - Annual Volume 2023 [Working Title]. IntechOpen, 2023. http://dx.doi.org/10.5772/intechopen.111845.
Full textAbstract:
Epithelial cells play a major role in animal and human homeostasis because they selectively regulate the exchange of solutes between two given media, such as blood or urine. Cardiac glycosides (CG) are a group of highly toxic compounds whose best therapeutic known effect is on heart, although recent evidence has shown that it exerts a wide range of physiological effects on cells and tissues other than the heart. Prostaglandins, on the other hand, are a group of lipids that produce diverse physiological and pathological effects among which inflammation stands out. In this chapter, we describe that cardiac glycosides modulate key features of epithelial cell physiology, including cell-cell contact junctional complexes, cilliogenesis, and gap junction-mediated intercellular communication (GJIC) in epithelial cells. Prostaglandin PGE2 also modulates GJIC through a different signaling pathway. In addition, we describe that CG induce paracrine release of prostaglandin PGE2, which in turn modulates GJIC by itself.
7
Pearce, Simon H. S., and Catherine J. Owen. "Endocrine Autoimmunity." In Oxford Textbook of Endocrinology and Diabetes 3e, edited by John A. H. Wass, Wiebke Arlt, and Robert K. Semple, 50–58. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780198870197.003.0007.
Full textAbstract:
The elucidation of the molecular basis for the rare monogenic polyendocrinopathy syndromes including autoimmune polyendocrinopathy type 1, has also allowed novel insights into key points of normal immune homeostasis such as thymic T-lymphocyte antigen receptor selection and the role of peripheral regulatory T cells. These fundamental advances have had far-reaching implications beyond those for endocrine patients. In contrast, the common, complex autoimmune endocrinopathies have been shown to be determined by numerous genetic variants within immune system receptors and signalling pathways along with a small number of variants in the target tissue antigens. A variety of environmental risk factors have been identified for several of these conditions, but it remains to be clarified how these impact pathogenesis at a molecular level. Moreover, the mainstay of therapies for these conditions is hormone replacement and there remains a ‘translational gap’ whereby information about disease pathogenesis has yet to be converted to useful patient advances.
8
Nasir, Aimen, Irum Shahzadi, and Ismat Nawaz. "Molecular Mechanisms and Strategies Contributing toward Abiotic Stress Tolerance in Plants." In Abiotic Stress in Plants - Adaptations to Climate Change [Working Title]. IntechOpen, 2023. http://dx.doi.org/10.5772/intechopen.109838.
Full textAbstract:
Plants respond to climate change via sensing the extreme environmental conditions at cell level, which initiated significant changes in their physiology, metabolism, and gene expression. At the cell membrane, plants activate certain genes (like GRP, PRP, AGP) to provide strengthening to cell wall. Drought and salinity stress tolerance attained by osmotic adjustments, activation of transcriptional factors (like AREB, ABF, DREB2), and regulation of Na+ homeostasis via transporters (like NSCC, NHX1, SOS1, HKT1, LTC1). For adaptations to chilling and frost stress, plants use hydrophobic barriers (waxes/cuticles), antinucleator (cryoprotective glycoprotein), and antifreeze proteins. Higher expression of HSPs (heatshock proteins such as HSP70, HSP100, HSP90, HSP60) is important for thermal tolerance. Tolerance to heavy metal (HM) stress can be achieved via vacuolar sequestration and production of phytochelatin, organic acids and metallothionein. ROS generated due to abiotic stresses can be alleviated through enzymatic (APX, CAT, POD, SOD, GR, GST) and nonenzymatic (ascorbate, glutathione, carotenoids, flavonoids) antioxidants. Genetic manipulation of these genes in transgenic plants resulted in better tolerance to various abiotic stresses. Genetic engineering of plants through various genome editing tools, such as CRISPR/Cas9, improve the abiotic stress tolerance as well as enhance the crops’ quality, texture, and shelf life.
9
Ježek, Petr, Blanka Holendová, Martin Jabůrek, Jan Tauber, Andrea Dlasková, and Lydie Plecitá-Hlavatá. "Redox Signaling is Essential for Insulin Secretion." In Type 2 Diabetes [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.94312.
Full textAbstract:
In this review, we place redox signaling in pancreatic β-cells to the context with signaling pathways leading to insulin secretion, acting for example upon the action of incretins (GLP-1, GIP) and the metabotropic receptor GPR40. Besides a brief description of ion channel participation in depolarization/repolarization of the plasma membrane, we emphasize a prominent role of the elevated glucose level in pancreatic β-cells during glucose-stimulated insulin secretion (GSIS). We focus on our recent findings, which revealed that for GSIS, not only elevated ATP synthesis is required, but also fundamental redox signaling originating from the NADPH oxidase 4- (NOX4-) mediated H2O2 production. We hypothesized that the closing of the ATP-sensitive K+ channel (KATP) is only possible when both ATP plus H2O2 are elevated in INS-1E cells. KATP alone or with synergic channels provides an element of logical sum, integrating both metabolic plus redox homeostasis. This is also valid for other secretagogues, such as branched chain ketoacids (BCKAs); and partly for fatty acids (FAs). Branched chain aminoacids, leucine, valine and isoleucine, after being converted to BCKAs are metabolized by a series of reactions resembling β-oxidation of FAs. This increases superoxide formation in mitochondria, including its portion elevated due to the function of electron transfer flavoprotein ubiquinone oxidoreductase (ETF:QOR). After superoxide conversion to H2O2 the oxidation of BCKAs provides the mitochondrial redox signaling extending up to the plasma membrane to induce its depolarization together with the elevated ATP. In contrast, experimental FA-stimulated insulin secretion in the presence of non-stimulating glucose concentrations is predominantly mediated by GPR40, for which intramitochondrial redox signaling activates phospholipase iPLA2γ, cleaving free FAs from mitochondrial membranes, which diffuse to the plasma membrane and largely amplify the GPR40 response. These events are concomitant to the insulin release due to the metabolic component. Hypothetically, redox signaling may proceed by simple H2O2 diffusion or via an SH-relay enabled by peroxiredoxins to target proteins. However, these aspects have yet to be elucidated.
Reports on the topic "GTP Homeostasis"
1
Splitter, Gary A., Menachem Banai, and Jerome S. Harms. Brucella second messenger coordinates stages of infection. United States Department of Agriculture, January 2011. http://dx.doi.org/10.32747/2011.7699864.bard.
Full textAbstract:
Aim 1: To determine levels of this second messenger in: a) B. melitensiscyclic-dimericguanosinemonophosphate-regulating mutants (BMEI1448, BMEI1453, and BMEI1520), and b) B. melitensis16M (wild type) and mutant infections of macrophages and immune competent mice. (US lab primary) Aim 2: To determine proteomic differences between Brucelladeletion mutants BMEI1453 (high cyclic-dimericguanosinemonophosphate, chronic persistent state) and BMEI1520 (low cyclicdimericguanosinemonophosphate, acute virulent state) compared to wild type B. melitensisto identify the role of this second messenger in establishing the two polar states of brucellosis. (US lab primary with synergistic assistance from the Israel lab Aim 3: Determine the level of Brucellacyclic-dimericguanosinemonophosphate and transcriptional expression from naturally infected placenta. (Israel lab primary with synergistic assistance from the US lab). B. Background Brucellaspecies are Gram-negative, facultative intracellular bacterial pathogens that cause brucellosis, the most prevalent zoonosis worldwide. Brucellosis is characterized by increased abortion, weak offspring, and decreased milk production in animals. Humans are infected with Brucellaby consuming contaminated milk products or via inhalation of aerosolized bacteria from occupational hazards. Chronic human infections can result in complications such as liver damage, orchitis, endocarditis, and arthritis. Brucellaspp. have the ability to infect both professional and non-professional phagocytes. Because of this, Brucellaencounter varied environments both throughout the body and within a cell and must adapt accordingly. To date, few virulence factors have been identified in B. melitensisand even less is known about how these virulence factors are regulated. Subsequently, little is known about how Brucellaadapt to its rapidly changing environments, and how it alternates between acute and chronic virulence. Our studies suggest that decreased concentrations of cyclic dimericguanosinemonophosphate (c-di-GMP) lead to an acute virulent state and increased concentrations of c-di-GMP lead to persistent, chronic state of B. melitensisin a mouse model of infection. We hypothesize that B. melitensisuses c-di-GMP to transition from the chronic state of an infected host to the acute, virulent stage of infection in the placenta where the bacteria prepare to infect a new host. Studies on environmental pathogens such as Vibrio choleraeand Pseudomonas aeruginosasupport a mechanism where changes in c-di-GMP levels cause the bacterium to alternate between virulent and chronic states. Little work exists on understanding the role of c-di-GMP in dangerous intracellular pathogens, like Brucellathat is a frequent pathogen in Israeli domestic animals and U.S. elk and bison. Brucellamust carefully regulate virulence factors during infection of a host to ensure proper expression at appropriate times in response to host cues. Recently, the novel secondary signaling molecule c-di-GMP has been identified as a major component of bacterial regulation and we have identified c-di-GMP as an important signaling factor in B. melitensishost adaptation. C. Major conclusions, solutions, achievements 1. The B. melitensis1453 deletion mutant has increased c-di-GMP, while the 1520 deletion mutant has decreased c-di-GMP. 2. Both mutants grow similarly in in vitro cultures; however, the 1453 mutant has a microcolony phenotype both in vitro and in vivo 3. The 1453 mutant has increased crystal violet staining suggesting biofilm formation. 4. Scanning electron microscopy revealed an abnormal coccus appearance with in increased cell area. 5. Proteomic analysis revealed the 1453 mutant possessed increased production of proteins involved in cell wall processes, cell division, and the Type IV secretion system, and a decrease in proteins involved in amino acid transport/metabolism, carbohydrate metabolism, fatty acid production, and iron acquisition suggesting less preparedness for intracellular survival. 6. RNAseq analysis of bone marrow derived macrophages infected with the mutants revealed the host immune response is greatly reduced with the 1453 mutant infection. These findings support that microlocalization of proteins involved in c-di-GMP homeostasis serve a second messenger to B. melitensisregulating functions of the bacteria during infection of the host.
2
Chalutz, Edo, Michael Wisniewski, Samir Droby, Yael Eilam, and Ilan Chet. Mode of Action of Yeast Biocontrol Agents of Postharvest Diseases of Fruits. United States Department of Agriculture, June 1996. http://dx.doi.org/10.32747/1996.7613025.bard.
Full textAbstract:
In a previous BARD-supported study, three of the investigators of this research were involved in a study on biological control of postharvest diseases of citrus and deciduous fruits. Several naturally occurring, non-antibiotic producing yeast antagonists were identified. Application of some of these antagonists resulted in very high levels of biocontrol under laboratory conditions but lower efficacy in semi-commercial tests. It was felt that the lack of knowledge on the mode of action of the biocontrol agents was limiting their efficient use. The current study was aimed at narrowing this gap in our knowledge. Two specific objectives were outlined: to study the mechanism by which calcium salts enhance biocontrol activity and to determine the role, if any, of the yeast extracellular materials and/or enzymes which degrade fungal cell walls during the interaction between the antagonists, the pathogen and the host. CaCl2 but not MgCl2, inhibited spore germination, and germ-tube elongation of Botrytis cinerea, Penicillium expansum and P. digitatum in culture. It also inhibited the pectinolytic activity of the pathogens. Biocontrol of apple decay by isolate 182 of Candida oleophila, an effective biocontrol agent, was enhanced by the addition of CaCl2 whereas there was no effect on the biocontrol activity of isolate 247 of this yeast. Similarly, CaCl2 enhanced efficacy of the US-7 isolate of Pichia guilliermondii in reducing infection of P. digitatum in citrus fruit. CaCl2 by itself also reduced the infection of peel wounds and stimulated ethylene production by grapefruit peel. This antagonist exhibited a very high ability to maintain cytosolic Ca2+ homeostasis when exposed to high CaCl2 concentrations. It is postulated, therefore, that enhanced biocontrol activity by calcium is the result of direct inhibition of the pathogen by calcium ions on spore germination and metabolism and indirectly due to the ability of the biocontrol agent to maintain normal metabolism in the presence of high levels of calcium. The extracellular materials produced by P. guilliermondii in culture and on the fruit inhibited, at low concentrations, the pathogen in culture and reduced percent infection of the fruit. The direct inhibition of the pathogen by these materials may thus be involved in the mode of action of the antagonist. This study contributed to our knowledge on the action of calcium salts and the yeast antagonist extracellular materials on biocontrol activity and will contribute to a more efficient use of this technology in the control of postharvest diseases of fruits.