Academic literature on the topic 'Stress signalling pathway'
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Journal articles on the topic "Stress signalling pathway"
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MATHIAS, Shalini, Louis A. PEÑA, and Richard N. KOLESNICK. "Signal transduction of stress via ceramide." Biochemical Journal 335, no. 3 (November 1, 1998): 465–80. http://dx.doi.org/10.1042/bj3350465.
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The sphingomyelin (SM) pathway is a ubiquitous, evolutionarily conserved signalling system analogous to conventional systems such as the cAMP and phosphoinositide pathways. Ceramide, which serves as second messenger in this pathway, is generated from SM by the action of a neutral or acidic SMase, or by de novosynthesis co-ordinated through the enzyme ceramide synthase. A number of direct targets for ceramide action have now been identified, including ceramide-activated protein kinase, ceramide-activated protein phosphatase and protein kinase Cζ, which couple the SM pathway to well defined intracellular signalling cascades. The SM pathway induces differentiation, proliferation or growth arrest, depending on the cell type. Very often, however, the outcome of signalling through this pathway is apoptosis. Mammalian systems respond to diverse stresses with ceramide generation, and recent studies show that yeast manifest a form of this response. Thus ceramide signalling is an older stress response system than the caspase/apoptotic death pathway, and hence these two pathways must have become linked later in evolution. Signalling of the stress response through ceramide appears to play a role in the development of human diseases, including ischaemia/reperfusion injury, insulin resistance and diabetes, atherogenesis, septic shock and ovarian failure. Further, ceramide signalling mediates the therapeutic effects of chemotherapy and radiation in some cells. An understanding of the mechanisms by which ceramide regulates physiological and pathological events in specific cells may provide new targets for pharmacological intervention.
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Šrámek, Jan, Vlasta Němcová-Fürstová, and Jan Kovář. "Molecular Mechanisms of Apoptosis Induction and Its Regulation by Fatty Acids in Pancreatic β-Cells." International Journal of Molecular Sciences 22, no. 8 (April 20, 2021): 4285. http://dx.doi.org/10.3390/ijms22084285.
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Pancreatic β-cell failure and death contribute significantly to the pathogenesis of type 2 diabetes. One of the main factors responsible for β-cell dysfunction and subsequent cell death is chronic exposure to increased concentrations of FAs (fatty acids). The effect of FAs seems to depend particularly on the degree of their saturation. Saturated FAs induce apoptosis in pancreatic β-cells, whereas unsaturated FAs are well tolerated and are even capable of inhibiting the pro-apoptotic effect of saturated FAs. Molecular mechanisms of apoptosis induction by saturated FAs in β-cells are not completely elucidated. Saturated FAs induce ER stress, which in turn leads to activation of all ER stress pathways. When ER stress is severe or prolonged, apoptosis is induced. The main mediator seems to be the CHOP transcription factor. Via regulation of expression/activity of pro- and anti-apoptotic Bcl-2 family members, and potentially also through the increase in ROS production, CHOP switches on the mitochondrial pathway of apoptosis induction. ER stress signalling also possibly leads to autophagy signalling, which may activate caspase-8. Saturated FAs activate or inhibit various signalling pathways, i.e., p38 MAPK signalling, ERK signalling, ceramide signalling, Akt signalling and PKCδ signalling. This may lead to the activation of the mitochondrial pathway of apoptosis, as well. Particularly, the inhibition of the pro-survival Akt signalling seems to play an important role. This inhibition may be mediated by multiple pathways (e.g., ER stress signalling, PKCδ and ceramide) and could also consequence in autophagy signalling. Experimental evidence indicates the involvement of certain miRNAs in mechanisms of FA-induced β-cell apoptosis, as well. In the rather rare situations when unsaturated FAs are also shown to be pro-apoptotic, the mechanisms mediating this effect in β-cells seem to be the same as for saturated FAs. To conclude, FA-induced apoptosis rather appears to be preceded by complex cross talks of multiple signalling pathways. Some of these pathways may be regulated by decreased membrane fluidity due to saturated FA incorporation. Few data are available concerning molecular mechanisms mediating the protective effect of unsaturated FAs on the effect of saturated FAs. It seems that the main possible mechanism represents a rather inhibitory intervention into saturated FA-induced pro-apoptotic signalling than activation of some pro-survival signalling pathway(s) or metabolic interference in β-cells. This inhibitory intervention may be due to an increase of membrane fluidity.
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Zhang, Shengrui, Klaus Apel, and Chanhong Kim. "Singlet oxygen-mediated and EXECUTER-dependent signalling and acclimation of Arabidopsis thaliana exposed to light stress." Philosophical Transactions of the Royal Society B: Biological Sciences 369, no. 1640 (April 19, 2014): 20130227. http://dx.doi.org/10.1098/rstb.2013.0227.
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Plants respond to environmental changes by acclimation that activates defence mechanisms and enhances the plant's resistance against a subsequent more severe stress. Chloroplasts play an important role as a sensor of environmental stress factors that interfere with the photosynthetic electron transport and enhance the production of reactive oxygen species (ROS). One of these ROS, singlet oxygen ( 1 O 2 ), activates a signalling pathway within chloroplasts that depends on the two plastid-localized proteins EXECUTER 1 and 2. Moderate light stress induces acclimation protecting photosynthetic membranes against a subsequent more severe high light stress and at the same time activates 1 O 2 -mediated and EXECUTER-dependent signalling. Pre-treatment of Arabidopsis seedlings with moderate light stress confers cross-protection against a virulent Pseudomonas syringae strain. While non-pre-acclimated seedlings are highly susceptible to the pathogen regardless of whether 1 O 2 - and EXECUTER-dependent signalling is active or not, pre-stressed acclimated seedlings without this signalling pathway lose part of their pathogen resistance. These results implicate 1 O 2 - and EXECUTER-dependent signalling in inducing acclimation but suggest also a contribution by other yet unknown signalling pathways during this response of plants to light stress.
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Desideri, Enrico, and L. Miguel Martins. "Mitochondrial Stress Signalling: HTRA2 and Parkinson's Disease." International Journal of Cell Biology 2012 (2012): 1–6. http://dx.doi.org/10.1155/2012/607929.
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Mitochondria are cellular energy generators whose activity requires a continuous supply of oxygen. Recent genetic analysis has suggested that defects in mitochondrial quality control may be key factors in the development of Parkinson’s disease (PD). Mitochondria have a crucial role in supplying energy to the brain, and their deterioration can affect the function and viability of neurons, contributing to neurodegeneration. These organelles can sow the seeds of their own demise because they generate damaging oxygen-free radicals as a byproduct of their intrinsic physiological functions. Mitochondria have therefore evolved specific molecular quality control mechanisms to compensate for the action of damaging agents such as oxygen-free radicals. PTEN-induced putative kinase 1 (PINK1) and high-temperature-regulated A2 (HTRA2), a mitochondrial protease, have recently been proposed to be key modulators of mitochondrial molecular quality control. Here, we review some of the most recent advances in our understanding of mitochondria stress-control pathways, focusing on how signalling by the p38 stress kinase pathway may regulate mitochondrial stress by modulating the activity of HTRA2 via PINK1 and cyclin-dependent kinase 5 (CDK5). We also propose how defects in this pathway may contribute to PD.
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Ma, Chen-Yu, Yu-Qian Ma, and Min Deng. "Mechanism of Zhen Wu Decoction in the Treatment of Heart Failure Based on Network Pharmacology and Molecular Docking." Evidence-Based Complementary and Alternative Medicine 2022 (March 15, 2022): 1–10. http://dx.doi.org/10.1155/2022/4877920.
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Heart failure (HF) is a serious manifestation or advanced stage of various cardiovascular diseases, and its mortality and rehospitalization rate are still on the rise in China. Based on the network pharmacology method, 59 components of Zhen Wu decoction (ZWD) and 83 target genes related to HF were obtained. Through the PPI network, four potential therapeutic targets were identified: AKT1, IL6, JUN, and MAPK8. The beneficial components of ZWD might intervene HF through the AGE-RAGE signalling pathway in the diabetes component, fluid shear stress and atherosclerosis, the TNF signalling pathway, TB, and Kaposi sarcoma related herpesvirus infection, according to a KEGG enrichment study. The protein interaction network of candidate targets was constructed by the STRING database, and the protein interaction network was clustered by MEODE software. GO and KEGG enrichment analyses were performed on the core modules obtained by clustering. Finally, AutoDock Vina software was used for molecular docking verification of key targets and active ingredients. The result was that 75 active ingredients and 109 genes were screened as potential active ingredients and potential targets of Shengjie Tongyu decoction for CHF treatment. The main active components were quercetin, luteolin, kaempferol, dehydrated icariin, isorhamnetin, formononetin, and other flavonoids. Il-6, MAPK1, MAPK8, AKT1, VEGFA, and JUN were selected as the core targets. Molecular docking showed that the key components were well connected with the target. GO enrichment analysis showed that Shengjie Tongyu decoction could play a role through multiple biological pathways including angiogenesis, regulation of endothelial cell proliferation, binding of cytokine receptors, negative regulation of apoptotic signalling pathways, regulation of nitric oxide synthase activity, and reactive oxygen metabolism. Key pathways mainly focus on the toll-like receptor signalling pathway, nod-like receptor signalling pathway, MAPK signalling pathway, mTOR signalling pathway, JAK-STAT signalling pathway, VEGF signalling pathway, and other pathways. Through molecular docking technology, it was found that a variety of effective components in ZWD, such as kaempferol. Molecular docking technology has preliminatively verified the network pharmacology and laid a foundation for the follow-up pharmacological research.
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Whitmarsh, A. J. "The JIP family of MAPK scaffold proteins." Biochemical Society Transactions 34, no. 5 (October 1, 2006): 828–32. http://dx.doi.org/10.1042/bst0340828.
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The components of MAPK (mitogen-activated protein kinase) signalling pathways can assemble into complexes that are co-ordinated by regulatory proteins including scaffold proteins. There is increasing evidence that scaffold proteins (i) maintain signalling specificity and facilitate the activation of pathway components, (ii) localize pathway components to particular subcellular sites or to specific targets, and (iii) serve as a point of signal integration to allow regulation of MAPK pathways by other signalling events in the cell. One family of scaffold proteins that regulate signalling by stress-activated MAPKs are the JIPs [JNK (c-Jun N-terminal kinase)-interacting proteins]. JIP proteins have been demonstrated to form complexes with specific JNK and p38 MAPK signalling modules and to play important roles in brain development, neuronal trafficking, apoptosis, β-cell function and insulin responses. Here, I briefly review our current understanding of the biochemical properties and physiological roles of JIP proteins.
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Verma, Poonam, Amit Ghosh, Manisha Ray, and Saurav Sarkar. "Lauric Acid Modulates Cancer-Associated microRNA Expression and Inhibits the Growth of the Cancer Cell." Anti-Cancer Agents in Medicinal Chemistry 20, no. 7 (July 3, 2020): 834–44. http://dx.doi.org/10.2174/1871520620666200310091719.
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Background: microRNAs are known to regulate various protein-coding gene expression posttranscriptionally. Fatty acids are cell membrane constituents and are also known to influence the biological activities of the cells like signal transduction, growth and differentiation of the cells, apoptosis induction, and other physiological functions. In our experiments, we used lauric acid to analyse its effects on human cancerous cell lines. Objective: Our objective was to speculate the miRNA expression profile in lauric acid treated and untreated cancerous cell lines and further study the metabolic pathways of the targeted tumour suppressor and oncogenes. Methods: The KB cells and HepG2 cells were treated with lauric acid and miRNA was isolated and the expression of tumour suppressor and oncogenic miRNA was measured by quantitative PCR. The untreated cells were used as control. The metabolic pathways of the target tumour suppressor and oncogenes were examined by GeneMANIA software. Results: Interestingly, the lauric acid treatment suppresses the expression of oncogenic miRNA and significantly upregulated the expression of some tumour suppressor miRNAs. GeneMANIA metabolic pathway revealed that the upregulated tumour suppressor miRNAs regulate several cancer-associated pathways such as DNA damage, signal transduction p53 class mediator, stem cell differentiation, cell growth, cell cycle phase transition, apoptotic signalling pathway, cellular response to stress and radiation, etc. whereas oncogenic miRNAs regulate the cancer-associated pathway like cell cycle phase transition, apoptotic signalling pathway, cell growth, response to oxidative stress, immune response activating cell surface protein signalling pathway, cyclin-dependent protein kinase activity, epidermal growth factor receptor signalling pathways, etc. Conclusion: In our study, we found that lauric acid works as an anticancer agent by altering the expression of miRNAs.
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Tiong, Yee Lian, Khuen Yen Ng, Rhun Yian Koh, Gnanajothy Ponnudurai, and Soi Moi Chye. "Melatonin Prevents Oxidative Stress-Induced Mitochondrial Dysfunction and Apoptosis in High Glucose-Treated Schwann Cells via Upregulation of Bcl2, NF-κB, mTOR, Wnt Signalling Pathways." Antioxidants 8, no. 7 (June 26, 2019): 198. http://dx.doi.org/10.3390/antiox8070198.
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Neuropathy is a complication that affects more than 50% of long-standing diabetic patients. One of the causes of diabetes neuropathy (DN) is the apoptosis of Schwann cells due to prolonged exposure to high glucose and build-up of oxidative stress. Melatonin is a hormone that has a known antioxidant property. In this study, we investigated the protective effect of melatonin on high glucose-induced Schwann cells’ apoptosis. Our results revealed that high glucose promoted apoptosis via mitochondrial-related oxidative stress and downregulated Bcl-2 family proteins in Schwann cells. In this signalling pathway, Bcl-2, Bcl-XL and Mcl-1 proteins were down-regulated while p-BAD and Puma proteins were up-regulated by high glucose treatment. Besides, we also proved that high glucose promoted apoptosis in Schwann cells through decreasing the p-NF-κB in the NF-κB signalling pathway. Key regulators of mTOR signalling pathway such as p-mTOR, Rictor and Raptor were also down-regulated after high glucose treatment. Additionally, high glucose treatment also decreased the Wnt signalling pathway downstream proteins (Wnt 5a/b, p-Lrp6 and Axin). Our results showed that melatonin treatment significantly inhibited high glucose-induced ROS generation, restored mitochondrial membrane potential and inhibited high glucose-induced apoptosis in Schwann cells. Furthermore, melatonin reversed the alterations of protein expression caused by high glucose treatment. Our results concluded that melatonin alleviates high glucose-induced apoptosis in Schwann cells through mitigating mitochondrial-related oxidative stress and the alterations of Bcl-2, NF-κB, mTOR and Wnt signalling pathways.
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Zhou, Xiang, Guoyin An, and Xiang Lu. "Hydrogen sulfide attenuates the development of diabetic cardiomyopathy." Clinical Science 128, no. 5 (November 13, 2014): 325–35. http://dx.doi.org/10.1042/cs20140460.
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H2S alleviates diabetic cardiomyopathy via attenuation of inflammation, oxidative stress and apoptosis. H2S may reduce high glucose-induced oxidative stress by activating the Nrf2/ARE pathway and exert anti-apoptotic effects by inhibiting JNK and p38 MAPK pathways and activating PI3K/Akt signalling.
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Thoms, Hazel C., and Lesley A. Stark. "The NF-κB Nucleolar Stress Response Pathway." Biomedicines 9, no. 9 (August 25, 2021): 1082. http://dx.doi.org/10.3390/biomedicines9091082.
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The nuclear organelle, the nucleolus, plays a critical role in stress response and the regulation of cellular homeostasis. P53 as a downstream effector of nucleolar stress is well defined. However, new data suggests that NF-κB also acts downstream of nucleolar stress to regulate cell growth and death. In this review, we will provide insight into the NF-κB nucleolar stress response pathway. We will discuss apoptosis mediated by nucleolar sequestration of RelA and new data demonstrating a role for p62 (sequestosome (SQSTM1)) in this process. We will also discuss activation of NF-κB signalling by degradation of the RNA polymerase I (PolI) complex component, transcription initiation factor-IA (TIF-IA (RRN3)), and contexts where TIF-IA-NF-κB signalling may be important. Finally, we will discuss how this pathway is targeted by aspirin to mediate apoptosis of colon cancer cells.
Dissertations / Theses on the topic "Stress signalling pathway"
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Darling, Nicola Jane. "Regulation of ER stress-induced cell death by the ERK1/2 signalling pathway." Thesis, University of Cambridge, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708709.
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Brown, Christopher Martin. "Intracellular mechanisms of stress-induced LTP impairment : a signalling pathway triggered by corticosterone in the rat hippocampus." Thesis, University of Bristol, 2016. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.715798.
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Hendricks, Kaylin. "Signalling molecule “calcium” improves germination and growth of Sorghum bicolor seedlings under salt stress." University of the Western Cape, 2021. http://hdl.handle.net/11394/8254.
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>Magister Scientiae - MScAbiotic stress, mainly in the form of extreme temperatures, drought and salinity has caused major crop losses worldwide, putting a severe strain on agriculture. Salinity severely limits plant growth and productivity and affects all aspects of the plant’s development including the most crucial stage; germination. This study investigated the effect of salt (NaCl) stress on Sorghum bicolor seedlings and the role of exogenously applied calcium (Ca2+) to ameliorate the effects of salt stress during germination. Sorghum seeds were germinated in the presence and absence of various NaCl (100, 200 and 300 mM) and Ca2+ (5, 15 and 35 mM) concentrations. Several assays including physiological (germination and growth assays), biochemical (osmolytes and oxidative stress markers), anatomical (epidermal and xylem layers) and expression profiles of key genes [antioxidant (SbSOD, SbAPX2 and SbCAT3), Salt Overly Sensitive (SbSOS1, 2 and 3) pathway enzymes and the vacuolar Na+/H+ exchanger antiporter2 (SbNHX2)] were investigated. Salt stress delayed germination and negatively affected growth as observed by the reduced root and shoot length and decreased fresh and dry weight. There was an increase in proline content and oxidative stress markers (H2O2 and MDA) under salt stress. Oxidative stress resulted in damage to the epidermal and xylem layers as observed on Scanning Electron Microscopy (SEM) images. Quantitative real-time polymerase chain reaction revealed that salt stress induced the expression of SbAPX2, SbCAT3 and SbSOS1 genes, whereas SbSOD4A, SbSOS2, SbSOS3 and SbNHX2 genes were not affected by salt. Exogenous application of Ca2+ counteracted the harmful effects of salt stress by improving germination efficiency, promoting seedling growth, reducing oxidative damage and the Na+/K+ ratio, indicating the protective effect. Ca2+ also effectively protected the epidermis and xylem layers from the severe damage caused by salt stress. In the presence of Ca2+ the expression of SbAPX2 and SbCAT3 was reduced except for the SbNHX2 gene, which increased by 65-fold compared to the control. The results obtained suggests that sorghum is able to respond to salt stress by inducing osmolytes, the antioxidant defence system as well as the SOS pathway. Furthermore, 5 mM Ca2+ was determined as the optimum Ca2+ concentration required to enhance sorghum’s tolerance to salt stress.
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Abrahams, Amaal. "Regulation of the anti-senescence factor, TBX2, by the UV stress signalling pathway and the mitotic cyclin dependent kinases." Doctoral thesis, University of Cape Town, 2007. http://hdl.handle.net/11427/24805.
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The T-box gene family has achieved great prominence in the field of developmental biology because its members have been demonstrated to play important roles in embryonic development and mutations within several T-box genes are associated with a number of human congenital diseases. Several lines of evidence have also implicated members of the T-box gene family in cell cycle regulation and in cancer. Importantly, the highly related T-box factors, Tbx2 and Tbx3, can suppress senescence through repressing the cyclin dependent kinase inhibitors, p21wAF11 c1P118011 and p19ARF. Both Tbx2 and Tbx3 have also been linked to several cancers primarily because their expression levels have been found to be deregulated in these cancers. However, despite the pivotal role that members of the T-box family play in a wide variety of biological processes, very little is known about the biochemical pathways that regulate their levels and transcriptional activity. In view of the detrimental consequences resulting from altered levels of T-box proteins, as seen both in developmental disorders and in certain cancers, the need to identify such pathways is important. The aim of this study was therefore to identify kinases that phosphorylate and regulate the levels and activity of Tbx2 with the view to understanding its role in cell cycle regulation and cancer. This study shows that the p38 stress mitogen-activated protein kinase, and the mitotic cyclin A/Cdk2 and cyclin B1/Cdk1, are direct regulators of Tbx2 both in vitro and in vivo. It is possible that Tbx2 and Tbx3 may contribute towards the oncogenic process through their anti-senescence function, especially since a dominant negative form of Tbx2 induces senescence in melanoma cells overexpressing Tbx2. However, very little is known about whether Tbx2 is indeed regulated during replicative- or stress-induced senescence. In this study, using a breast cancer cell line known to overexpress Tbx2, the Tbx2 protein is shown to be specifically phosphorylated by the p38 kinase in response to stress induced by ultraviolet irradiation. Using site-directed mutagenesis and in vitro kinase assays, serine residues 336, 623 and 675 in the Tbx2 protein were identified as p38 target sites. These sites are also shown to be phosphorylated in vivo. Importantly, western blotting, immunofluorescence and reporter assays reveal that this phosphorylation leads to increased Tbx2 protein levels, predominant nuclear localisation of the protein, and an increase in the ability of Tbx2 to repress the p21wAF11 c/P118011 promoter. These results show, for the first time, that the ability of Tbx2 to repress the p21 gene is enhanced in response to a stress-induced senescence pathway. This leads to a better understanding of the anti-senescence function of Tbx2. The ability of Tbx2 to function as an anti-senescence factor, as well as its altered regulation being associated with certain cancers, suggests that"its levels may need to be tightly regulated during the cell cycle. Indeed, the Tbx2 protein was previously shown to be regulated during the various phases of the cell cycle, peaking at G2. The changes in the Tbx2 protein levels did not match changes in Tbx2 mRNA levels, suggesting that the protein may be regulated by posttranslational modifications such as phosphorylation. This study shows that the phosphorylation status of Tbx2 is regulated during the cell cycle with levels of phosphorylation peaking in G2 and M, in mouse and human cells respectively. Phosphorylation was shown to be specifically mediated by the mitotic kinases as demonstrated in experiments when the mitotic kinase inhibitor, olomoucine, was included. This study provides data to suggest that Tbx2 may be regulated differently during the cell cycle in mouse and human cells. Using site-directed mutagenesis and in vitro kinase assays, Tbx2 was found to be specifically phosphorylated at serine residues 192 and 336 by cyclin A/Cdk2 and serine residues 336 and 342 by cyclin 81/Cdk1. These sites are also targets for phosphorylation in vivo since mutating them altered the phosphorylation status ofTbx2. Moreover, both cyclin A and 81 were shown to bind Tbx2 in vitro and in vivo and the minimal region required for binding was mapped to its DNA-binding domain. Importantly, immunofluorescence demonstrates that the Tbx2 protein localises specifically to the nucleus at G2; this translocation was shown to be blocked in the presence of olomoucine. Furthermore, western blot analyses and reporter assays showed that pseudo-phosphorylation by cyclin 81/ Cdk1, but not cyclin A/Cdk2, leads to increased Tbx2 protein levels and an increase in the ability of Tbx2 to repress the p21wAFtiCIPt!Sou promoter. These results disclose, for the first time, that phosphorylation by cyclin A/Cdk2 and cyclin 81/Cdk1 of the Tbx2 protein regulates its activity. This data provide additional evidence to support a role for Tbx2 in the G2 and/or M phase of the cell cycle.
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Pacini, Laura. "Deregulation of TLR9 signalling pathway in human keratinocytes by E6 and E7 oncoproteins from beta human papillomavirus type 38." Thesis, Lyon, 2016. http://www.theses.fr/2016LYSE1321/document.
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Les virus du papillome humain (HPV) sont des virus à ADN double-brin encapsidés appartenant à la famille des Papillomaviridae ayant un tropisme distinct pour les épithéliums squameux de type muqueux ou cutanés. Jusqu'à présent, plus de 200 types de HPV ont été isolés et regroupés dans un arbre phylogénétique composé de 5 genres nommés alpha, beta, gamma, mu et nu. Parmi eux, les types HPV muqueux à haut risque appartenant au genre alpha ont été associés au cancer du col de l'utérus ainsi qu'à des sous-groupes de carcinomes ano-génitaux et de la tête et du cou. Ces virus sont responsables d'environ 5% de tous les cancers viro-induits. Les types bêta du HPV ont un tropisme pour la peau et pourraient être impliqués dans le développement du cancer de la peau non mélanique (NMSC), en association avec la lumière ultraviolette (UV). Ainsi, les modèles expérimentaux in vitro et in vivo ont démontré les propriétés de transformation des oncoprotéines E6 et E7 du type HPV bêta 38. De plus, des études sur le modèle de souris transgénique, où E6 et E7 du HPV38 sont exprimés au niveau de la couche basale non différenciée de l'épithélium sous le contrôle du promoteur du gène humain de la kératine (K14), ont montré une très forte susceptibilité de la peau à la carcinogenèse induite par les UV par rapport aux animaux de type sauvage. Tout aussi important que leur capacité à promouvoir la transformation cellulaire, les virus oncogènes ont développé différentes stratégies pour prendre le dessus sur le système immunitaire de l'hôte, favorisant ainsi l'établissement d'une infection persistante. Par conséquent, savoir si des virus oncogènes potentiels ont la capacité d'interférer avec la réponse immunitaire pourrait fournir des preuves supplémentaires de leur implication dans la cancérogenèse humaine. Ici, nous montrons que les oncoprotéines E6 et E7 de HPV38 suppriment l'expression de Tolllike 9 (TLR9), récepteur des ADN double-brins, en favorisant l'accumulation de ΔNp73α, un antagoniste de p53 et p73. Des expériences d'immunoprécipitation de la chromatine ont montré que ΔNp73α fait partie d'un complexe de régulation négative transcriptionnelle qui se lie à un élément de réponse NF-kappaB dans le promoteur TLR9. Fait intéressant, l'expression ectopique de TLR9 dans des cellules HPV38 E6E7 a entraîné une accumulation des inhibiteurs du cycle cellulaire p21WAF1/Cip1 et p27kip1, une réduction de l'activité kinase associée à CDK2 et l'inhibition de la prolifération cellulaire. Ensemble, ces données indiquent que TLR9 est impliqué dans d'autres événements, en plus de la réponse immunitaire innée. Par conséquent, nous avons constaté que le traitement des kératinocytes humains primaires (HPK) avec différents stress cellulaires, par exemple l'irradiation aux UV, la doxorubicine et le traitement H2O2, conduisent à une induction de la transcription de TLR9. Cet évènement induit par les UV est arbitré par le recrutement de plusieurs facteurs de transcription sur le promoteur TLR9, tels que p53, NF-kappaB p65 et c-Jun. L'expression de E6 et E7 de HPV38 affecte fortement le recrutement de ces facteurs de transcription sur le promoteur TLR9, avec comme conséquence l'affaiblissement de l'expression du gène TLR9. En résumé, nos données montrent que HPV38, de manière similaire à d'autres virus avec une activité oncogénique bien connue, peut inhiber 'expression de TLR9. Plus important encore, nous mettons en évidence une nouvelle fonction de TLR9 dans le contrôle de la réponse cellulaire aux stress et nous montrons que E6 et E7 de HPV38 sont capables d'interférer avec un tel mécanisme. Ces résultats confirment le rôle des types HPV bêta dans la carcinogenèse de la peau, en fournissant des informations supplémentaires sur leur contribution précise dans le processus multi-étapes de développement du cancerThe human papillomaviruses (HPV) consist of a group of capsid-enclosed double-stranded deoxyribonucleic acid (dsDNA) viruses from the Papillomaviridae family that display a distinct tropism for mucosal or cutaneous squamous epithelia. Until now, more than 200 types of HPV have been isolated and grouped into a phylogenetic tree composed of 5 genera (alpha, beta, gamma, mu and nu papillomaviruses). Among them, the mucosal high-risk HPV types that belong to the genus alpha have been associated with cervical cancer as well as a subset of anogenital and head and neck carcinomas. They are responsible for approximately 5% of all virus-induced cancers. Beta HPV types have a skin tropism and have been suggested to be involved, together with ultraviolet light (UV), in the development of non-melanoma skin cancer (NMSC). For instance, in vitro and in vivo experimental models highlight the transforming properties of beta HPV38 E6 and E7. Specifically, studies of transgenic mouse model, where HPV38 E6 and E7 are expressed in the undifferentiated basal layer of epithelia under the control of the Keratin 14 (K14) promoter, showed a very high susceptibility to UV-induced skin carcinogenesis in comparison to the wild-type animals. Equally important as their ability to promote cellular transformation, oncogenic viruses have different strategies to overtake the host immune system thus guaranteeing persistent infection. Therefore, understanding whether potential oncogenic viruses have the ability to interfere with the immune response could provide additional evidence relating to their involvement in human carcinogenesis. Here, we show that the E6 and E7 oncoproteins from HPV38 suppress the expression of the dsDNA innate immune sensor Toll-like receptor 9 (TLR9) by promoting the accumulation of ΔNp73α, an antagonist of p53 and p73. Chromatin immunoprecipitation experiments showed that ΔNp73α is part of a negative transcriptional regulatory complex that binds to a NF-κB responsive element within the TLR9 promoter. Interestingly, ectopic expression of TLR9 in HPV38 E6E7 cells resulted in an accumulation of the cell cycle inhibitors p21WAF/Cip1 and p27Kip1, reduction of CDK2-associated kinase activity and inhibition of cellular proliferation. Together these data indicate that TLR9 is involved in additional events, besides the innate immune response. Accordingly, we observed that the treatment of human primary keratinocytes (HPKs) with different cellular stresses, e.g. UV irradiation, doxorubicin and H2O2 treatment, results in TLR9 up-regulation. This UVinduced event is mediated by the recruitment of several transcription factors to the TLR9 promoter, such as p53, NF-kB p65 and c-Jun. The expression of HPV38 E6 and E7 strongly affect the recruitment of these transcription factors to the TLR9 promoter, with consequent impairment of TLR9 gene expression. In summary, our data show that HPV38, similarly to other viruses with well-known oncogenic activity, can down-regulate TLR9. Most importantly, we highlight a novel function of TLR9 in controlling the cellular response to stresses and we show that HPV38 E6 and E7 are able to interfere with such mechanism. These findings further support the role of beta HPV types in skin carcinogenesis, providing additional insight into their precise contribution to the multistep process of cancer development
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Minnaar, Estella Lily. "Regional neurochemical characterization of the flinders sensitive line rat with regard to glutamate-nitric oxide and cGMP signalling pathways / Estella Lily Minnaar." Thesis, North-West University, 2008. http://hdl.handle.net/10394/4214.
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The serious nature of MDD has intensified the need to identify and elucidate new neurobiological targets for antidepressant drug action. Depression presents with evidence for degenerative pathology that relates to disturbances in excitatory glutamatergic pathways, particularly the N-methyl-D-aspartate (NMDA) receptormediated release of the pleiotropic molecule, nitric oxide (NO), and cyclic guanosine monophosphate (cGMP). The contribution of the glutamate-NO/cGMP pathway may
realize great importance as a fundamental substrate underlying the pathophysiology
of major depression. In the next generation of antidepressant drugs, the nitric oxide pathway could playa dynamic role in addressing urgent therapeutic needs. In this study, we have used a genetic model of depression, the Flinders Sensitive Line (FSL) rat, to investigate the surrogate markers of the NO/cGMP pathway.
The aim was to determine whether the depressive-like behaviour of the
hypercholinergic FSL rat is accompanied by altered activation of the NO/cGMP
pathway. To this end, the extent to which the FSL and Flinders Resistant Line (FRL)
rats differ neurochemically with regard to basal hippocampal and frontal cortical
NOS-activity, as well as nitric oxide (NO) and cGMP accumulation, were determined.
Additionally, select behavioural assessments were performed to confirm the
anxiogenic phenotype of the FSL strain.
For neurochemical determinations a sensitive fluorometric reversed phase highperformance
liquid chromatographic (HPLC) assay was developed to analyze total
nitrite and nitrate in brain tissue. Nitrate was enzymatically converted to nitrite before
derivatization with 2,3-diaminonaphthalene (DAN). The stable and highly fluorescent
product, 2,3-naphthotriazole (NAT), was quantified. Secondly, the quantity of the
amino acid L-citrulline was measured by HPLC with electrochemical detection after
o-phthalaldehyde (OPA) derivatization. L-citrulline formation was used as an index
for nNOS activity. Finally, a direct, competitive enzyme immunoassay kit was used to
determine the downstream activity of the NO-pathway in brain tissue.
FSL rats were compared to FRL rats with respect to sensitivity to serotonin 5-HT1A .
receptor-mediated hypothermia under our lab-conditions. The Open Field Test (OFT)
behavioural assessment was performed to compare FSL with FRL groups under
baseline conditions according to their level of inherent anxiety. The parameters used
to measure anxiety were number of line crosses (locomotor activity), time spent in
middle blocks and social interaction time between pairs of rats. As an additional
behavioural assessment, the Forced Swim Test (FST) was performed to assess
behavioural restraint measured as time of immobility.
Basal cGMP levels in the frontal cortex were found to be significantly less in FSL
than in FRL rats, whereas the levels in the hippocampus did not differ significantly.
No other significant differences with respect to NO and nNOS activity were apparent
in either of the brain areas. The hypothermia test confirmed a significantly greater
decrease in temperature in the FSL rat than the FRL rat. The FST did not confirm
any differences in immobility time between the two rat strains. In the OFT, FSL rat
groups exhibited behaviour that indicated significantly more anxiety than FRL rats.
Under basal conditions, FSL rats do not present with significant changes in markers
of the NO cascade in the hippocampus and frontal cortex compared to FRL controls,
including NOS activity as well as NO accumUlation. However, cGMP levels were
found to be significantly lower in the frontal cortex of FSL rats versus FRL rats,
although not in the hippocampus. Since the FSL rat is known to be hypercholinergic,
these data support an interaction between the NO/cGMP pathway and the
cholinergIc system in the frontal cortex but not hippocampus of FSL animals. The
mechanisms and implications of such a mutual involvement need further clarification.
Further, this anatomical differentiation may have important implications for
understanding the role of NO in the depressive-like behaviour of the FSL rat and,
indeed, may reveal more on the neurobiology and treatment of depression. Through
the performed behavioural assessments, the FSL and FRL rats were successfully
separated with respect to their anxiety phenotype as well as their heightened
response to serotonergic challenge, thus confirming a contribution of both the
serotonergic and cholinergic systems to the depressogenic nature of these animals.
As concluding remark can be said that under normal basal conditions markers of the
NO/cGMP signalling cascade are not altered in FSL vs FRL rats, although cGMP
levels are reduced in the frontal cortex of FSL rats, supportive of an NO-independent
mechanism of cGMP regulation, possibly involving ACh.Thesis (M.Sc. (Pharmacology)--North-West University, Potchefstroom Campus, 2009.
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Pai, Mangalore Govind [Verfasser], Ignacio [Gutachter] Rubio, Regine [Gutachter] Heller, and Fried JT [Gutachter] Zwartkruis. "The role of mTOR signalling pathway as a susceptibility factor in genotoxic stress-induced cell death / Mangalore Govind Pai ; Gutachter: Ignacio Rubio, Regine Heller, Fried J. T. Zwartkruis." Jena : Friedrich-Schiller-Universität Jena, 2016. http://d-nb.info/1177613492/34.
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Chaput, Carole. "Therapeutic functionalization of a rare neurodevelopmental and monogenic disease model based on the contribution of the HSF2 stress pathway." Electronic Thesis or Diss., Université Paris Cité, 2024. http://www.theses.fr/2024UNIP5190.
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Les troubles neurodéveloppementaux (TND) touchent environ 10 % des enfants et constituent une source majeure d'invalidité tout au long de la vie. Caractérisés par un développement défectueux du cerveau et une grande variabilité du tableau clinique des patients, qui compromet le diagnostic et l'émergence de solutions thérapeutiques, ils représentent un coût humain, sociétal et économique important. L'objectif de ce projet est de mieux comprendre une caractéristique commune des TND - la dérégulation des voies de réponse au stress - qui constituerait une clef de lecture pour comprendre ces pathologies. L'intégration des processus déclenchés par le stress est régie par les facteurs de transcription du choc thermique (HSF), qui sont fortement dérégulés dans plusieurs TND. Cela a deux conséquences : une altération de la réponse au stress des cellules neurales qui entraîne des défauts dans le développement du cerveau. Nous avons participé a montré que ces HSF sont essentiels au bon développement du cerveau. Plus précisément, l'équipe a démontré que HSF2 joue un rôle clef dans la régulation de la prolifération des cellules progénitrices et la migration neuronale dans le cortex en modulant l'expression de gène impliqués dans l'adhésion cellulaire. La modulation pharmacologique de cette voie pourrait donc offrir de nouvelles possibilités thérapeutiques. Dans une première étude, les mécanismes sous-jacents à la dérégulation des HSF ont été étudiés dans les cellules de patients atteints du syndrome de Rubinstein-Taybi (RSTS), un TND rare d'origine génétique causé par des mutations dans les gènes CREBBP ou EP300. Notre étude a montré une diminution des niveaux protéiques de HSF2 dans les fibroblastes et dans les modèles neuraux (2D et 3D) dérivés à partir de cellules souches pluripotentes induites (iPSC) provenant de patients RSTS. Cette diminution des niveaux protéiques de HSF2 résultait d'un défaut d'acétylation par CBP ou EP300, conduisant à l'ubiquitination et à la dégradation par le protéasome. En conséquence, les cellules RSTS présentaient une altération de la réponse au stress et une réduction de l'expression de gènes essentiels au développement neural, en particulier la N-cadhérine. La restauration des niveaux de HSF2, soit par l'inhibition du protéasome, soit par des mutations imitant l'acétylation, a permis de rétablir à la fois la réponse au stress et l'expression des gènes du neurodéveloppement. Nous avons constaté que la perturbation de la voie CBP/EP300-HSF2-N-cadhérine est récapitulée dans les modèles neuraux RSTS, qui présentent des anomalies de prolifération liées à une altération de l'adhésion cellule-cellule, en particulier dans la voie de la N-cadhérine. Sur la base de ces résultats et en collaboration avec Ksilink, mon projet de thèse CIFRE vise à développer un modèle cellulaire de TND basé sur les patients RSTS. Ce modèle permettra d'explorer comment les perturbations de la voie HSF pourraient contribuer à divers TND. Pour atteindre cet objectif, j'ai d'abord généré un mutant HSF2 qui mime la forme acétylée de la protéine dans les iPSC dérivés de fibroblastes de patients RSTS. En utilisant ce modèle isogénique comme référence, j'ai développé et validé un modèle de culture neural bidimensionnel et identifié de nouvelles cibles et phénotypes dépendants de HSF2 via une approche multiparamétrique allant de la transcriptomique à haut débit à des analyses morphologiques des cellules. Cette approche a permis d'identifier le facteur pro neuronal, ASCL1, et un phénotype morphologique, la formation de rosettes, comme clefs de lecture pour l'analyse par imagerie à haut contenu. Sur la base de ces deux phénotypes, j'ai utilisé le modèle neural pour cribler une sélection de molécules à potentiel thérapeutique par imagerie à haut contenu. Ces travaux ouvriront la voie à de nouvelles approches thérapeutiques visant à moduler les voies de réponse au stress, offrant ainsi de nouvelles possibilités de traitement des TNDNeurodevelopmental disorders (NDD) affect around 10% of children and are a major source of lifelong disability. Characterised by defective brain development and great variability in the clinical picture of patients, which compromises diagnosis and the emergence of therapeutic solutions, they represent a significant human, societal and economic cost. The aim of this project is to gain a better understanding of a common feature of NDDs - the deregulation of stress response pathways - which could provide a readout to understanding these pathologies. The integration of processes triggered by stress is governed by heat shock transcription factors (HSFs), which are strongly deregulated in several NDDs. This has two consequences: an altered stress response in neural cells leading to defects in brain development. We have helped to show that these HSFs are essential for proper brain development. More specifically, the team demonstrated that HSF2 plays a key role in regulating the proliferation of progenitor cells and neuronal migration in the cortex by modulating the expression of genes involved in cell adhesion. Pharmacological modulation of this pathway could therefore offer new therapeutic possibilities. In a first study, the mechanisms underlying HSF deregulation were investigated in cells from patients with Rubinstein-Taybi syndrome (RSTS), a rare genetic NDD caused by mutations in the CREBBP or EP300 genes. Our study showed a decrease in HSF2 protein levels in fibroblasts and in neural models (2D and 3D) derived from induced pluripotent stem cells (iPSCs) from RSTS patients. This decrease in HSF2 protein levels resulted from a defect in acetylation by CBP or EP300, leading to ubiquitination and degradation by the proteasome. As a result, RSTS cells showed an altered stress response and reduced expression of genes essential for neural development, in particular N-cadherin. Restoration of HSF2 levels, either by proteasome inhibition or by acetylation-mimicking mutations, restored both the stress response and the expression of neurodevelopmental genes. We found that disruption of the CBP/EP300-HSF2-N-cadherin pathway is recapitulated in RSTS neural models, which display proliferation abnormalities linked to altered cell-cell adhesion, particularly in the N-cadherin pathway. On the basis of these results and in collaboration with Ksilink, my CIFRE thesis project aims to develop a cellular model of NDD based on RSTS patients. This model will enable us to explore how perturbations in the HSF pathway could contribute to various NDDs. To achieve this objective, I first generated an HSF2 mutant that mimics the acetylated form of the protein in iPSCs derived from RSTS patient fibroblasts. Using this isogenic model as a reference, I developed and validated a two-dimensional neural culture model and identified new HSF2-dependent targets and phenotypes using a multiparametric approach ranging from high-throughput transcriptomics to cell morphological analyses. This approach made it possible to identify the pro-neuronal factor, ASCL1, and a morphological phenotype, rosette formation, as key readouts for analysis by high-content imaging. On the basis of these two phenotypes, I used the neural model to screen a selection of molecules with therapeutic potential using high-content imaging. This work will pave the way for new therapeutic approaches aimed at modulating stress response pathways, thereby opening up new possibilities for the treatment of NDD
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Samuels, Michael L. "Yeast stress signalling." Thesis, University College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368116.
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Kritsiligkou, Paraskevi. "Peroxiredoxins : yeast redox switches that regulate multiple cellular pathways." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/peroxiredoxins-yeast-redox-switches-that-regulate-multiple-cellular-pathways(fbb44664-5021-4dbc-88c7-64aef8a6c045).html.
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Peroxiredoxins are small ubiquitous cysteine-containing proteins that exhibit high reactivity to hydrogen peroxide. Apart from their role as antioxidants, detoxifying hydrogen peroxide to water, peroxiredoxins have been implicated in other cellular processes, such as protein folding and signalling. Using S. cerevisiae as a model organism, we utilised a variety of techniques to examine previously unexplored links between peroxiredoxins and mitochondrial function. Firstly, we characterised the role of Gpx3 in yeast mitochondria. Proteomic work revealed the presence of Gpx3 in the mitochondrial intermembrane space (IMS) and we characterised when, how and why Gpx3 can be found within the mitochondria. We showed that cells lacking Gpx3 have aberrant mitochondrial morphology and defective protein import capacity and inner membrane potential upon H2O2 stress. Gpx3 translocates to the IMS via a targeting sequence encoded from a non-AUG codon. This provides a novel and unique molecular mechanism that protects mitochondria from the exceptional oxidative stress which their activity imposes. Secondly, we focused on the role of Tsa1 upon protein aggregation-induced stress. Previous studies using the proline analogue AZC to cause protein misfolding revealed that protein aggregates are localised adjacent to mitochondria and mitochondrial ROS are generated in response. We questioned what effect this might have on mitochondrial function and we showed that upon AZC treatment there is a drop in respiratory rate, dependent on Tsa1. We questioned whether Tsa1, like other peroxiredoxins, is involved in regulating signalling cascades and we showed that cells that are lacking Tsa1 have alterations in the activity of the cAMP/PKA pathway. In parallel, we looked for differences both in the proteome and the transcriptome to understand what is the cause of the lethality of a tsa1 strain upon protein aggregation stress. We propose a mechanism where Tsa1 mediates a transcriptional response to protein misfolding stress via the activity of the heat shock transcription factor, Hsf1. Finally, we focused on the role of the mitochondrial peroxiredoxin Prx1. Under conditions where the mitochondrial matrix is oxidised, either genetically or by chemical addition, we showed than an apoptotic pathway is activated, dependent on the redox state of thioredoxin, Trx3. We showed that Trx3 can interact with Prx1 and loss of Prx1 also stops the induction of cell death. Analysis of the interactome of Trx3 unraveled the involvement of Bxl1/Ybh3, the yeast BH3 domain-containing protein and Aim9, a previously uncharacterised protein with kinase-like motifs, in the progression of cell death. The data presented in this thesis widens our understanding of the function of peroxiredoxins and their involvement in the regulation of cellular cascades that ensure correct mitochondrial function and responses to stress.
Books on the topic "Stress signalling pathway"
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Wentzel, Jolanda J., Ethan M. Rowland, Peter D. Weinberg, and Robert Krams. Biomechanical theories of atherosclerosis. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780198755777.003.0012.
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Atherosclerosis, the disease underlying most heart attacks and strokes, occurs predominantly at certain well-defined sites within the arterial system. Its development may therefore depend not only on systemic risk factors but also on locally varying biomechanical forces. There are three inter-related theories explaining the effect of biomechanics on atherosclerosis. In the first theory, a central role is played by lipid transport into the vessel wall, which varies as a result of mechanical forces. In the second theory, haemodynamic wall shear stress-the frictional force per unit area of endothelium arising from the movement of blood-activates signalling pathways that affect endothelial cell properties. In the third, strain-the stretch of the wall arising from changes in blood pressure-is the key biomechanical trigger. All three theories are discussed from historical, molecular, and clinical perspectives.
Book chapters on the topic "Stress signalling pathway"
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Ferrando, Alejandro, Pedro Carrasco, Juan Cruz Cuevas, Teresa Altabella, and Antonio F. Tiburcio. "Integrated Molecular Analysis of the Polyamine Metabolic Pathway in Abiotic Stress Signalling." In Plant Ecophysiology, 207–30. Dordrecht: Springer Netherlands, 2004. http://dx.doi.org/10.1007/978-1-4020-2728-4_8.
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Feng, Jia-fu. "Biomarkers of Oxidative Stress." In Targeting Cellular Signalling Pathways in Lung Diseases, 703–15. Singapore: Springer Singapore, 2021. http://dx.doi.org/10.1007/978-981-33-6827-9_32.
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Singh, Shilpy, Ruth Assumi, and Pooja Bhadrecha. "Crosstalk of MicroRNAs with Phytohormone Signalling Pathways." In Plant MicroRNAs and Stress Response, 257–76. Boca Raton: CRC Press, 2023. http://dx.doi.org/10.1201/9781003322214-15.
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Asif, Iqbal, Iqbal Mazhar, Alamzeb Madeeha, Fahad Shah, Akmal Mohammad, Anwar Shazma, Khan Asad Ali, et al. "Cross-Talk between Phytohormone-Signalling Pathways under Abiotic Stress Conditions." In Plant Growth Regulators for Climate-Smart Agriculture, 99–116. Boca Raton: CRC Press, 2021. http://dx.doi.org/10.1201/9781003109013-7.
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Sehrawat, Ankita, and Renu Deswal. "Proteomics Approach to Uncover Key Signalling Pathways in Brassica juncea in Abiotic and Biotic Stress." In The Brassica juncea Genome, 337–47. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-91507-0_19.
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Achhelal Yadav, Ms Bijal, Mr Akshat Sunil Jain, Mr Abhiram Rajesh Patil, and Ms Somya Rajesh Singh. "VERICIGUAT: A MIRACULOUS THERAPEUTIC AGENT FOR HEART FAILURE." In Futuristic Trends in Medical Sciences Volume 3 Book 13, 267–81. Iterative International Publishers, Selfypage Developers Pvt Ltd, 2024. http://dx.doi.org/10.58532/v3bdms13p2ch7.
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The NO-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway regulates cardiovascular function and is disturbed in heart failure (HF), resulting in diminished protection against myocardial damage. In HF, impaired NO-sGC-cGMP signalling is caused by decreased NO bioavailability and an altered redox state of sGC, which makes it less sensitive to NO. Cinaciguat, a sGC activator, raises cGMP levels by direct NO-independent sGC activation and may be especially beneficial under settings of increased oxidative stress and endothelial dysfunction, and therefore lower NO levels, at the price of an increased risk of hypotension. sGC stimulators, on the other hand (riociguat and vericiguat), increase sGC sensitivity to endogenous NO, resulting in a more physiological effect. The review focuses on the complete drug profile of Vericiguat.
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S, Deepa, Kalaivani S, Sathesh Kumar K, Mohammed Wasim Khan N, Anusha T, and Neeraja S. "HEAT SHOCK PROTEINS: THE CELLULAR SUPERHEROES UNVEILED!" In Futuristic Trends in Pharmacy & Nursing Volume 3 Book 6, 100–123. Iterative International Publishers, Selfypage Developers Pvt Ltd, 2024. http://dx.doi.org/10.58532/v3bipn6p1ch9.
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A family of molecular chaperones known as heat shock proteins (HSPs) is highly conserved and essential for cellular homeostasis and stress response control. HSPs were first recognised as stress-induced proteins, but they have now expanded beyond their typical functions in protein folding and unfolding to become key actors in a number of cellular processes. The goal of this review is to give a thorough summary of what is currently known about heat shock proteins, their various roles, and how they affect cellular physiology. Beginning with the taxonomy and structural organisation of HSPs, the review will go into detail about large families like Hsp70, Hsp90, Hsp60, and tiny HSPs. Emphasising the crucial role, they play in preserving proteostasis under physiological and stressful settings, their chaperoning actions in protein folding and refolding will be clarified. They will also be emphasised for their role in cellular trafficking and transport activities. The review will also cover how HSP expression is dynamically regulated in response to stressors such heat, oxidative stress, heavy metals, and infections. The discussion about complex mechanisms underlying HSP gene expression and how they interact with stress-responsive signalling pathways including the heat shock factor (HSF) pathway will be reviewed. HSPs have been connected to a variety of physiological processes outside of their typical tasks, such as modulation of apoptosis, cell cycle regulation, immunological responses, and neuroprotection. The evolving functions of HSPs in these processes and their effects on human health and disease will be examined in this review. Targeting HSPs in various clinical states may also have therapeutic benefits, which will be investigated. Notably, HSPs have been suggested as therapeutic targets for diseases associated with protein misfolding, cancer, and neurodegenerative disorders. In summary, this examination will provide you a thorough understanding of the diverse functions that heat shock proteins play in cellular physiology and stress response. The investigation of their roles in various cellular functions and their therapeutic potential highlights the significance of more study in this area to develop novel therapeutic interventions and approaches for managing human health and disease.
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"THE ROLE OF SPHINGOLIPIDS IN STRESS RESPONSES AND APOPTOSIS IN EUKARYOTES." In Signalling Pathways in Apoptosis, 101–18. CRC Press, 1999. http://dx.doi.org/10.1201/9781482298215-11.
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Teotia, Varsha, Jessica Pantuczek, Waseem Bashir Valiya Kalladi, John J. Murphy, and Kalpana Surendranath. "DNA Replication Stress and the Human Genome: Hurdles, Hijacks and Cell Health." In Biochemistry. IntechOpen, 2024. http://dx.doi.org/10.5772/intechopen.115004.
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During replication of the genetic material, cells often face hurdles that challenge DNA replication machinery, leading to replication stress. Multiple complex signalling pathways have evolved to counteract and overcome such challenges. However, DNA repair defects caused by inefficient functioning of the DNA damage response pathways (DDR) drive genomic instability, one of the hallmarks of cancer. Here, we review the known events in DNA replication that induce replication stress and the mechanisms deployed by DDR pathways to deal with and overcome replication stress. Since the defects in these molecular pathways are associated with tumour progression, we provide an update on the novel and promising druggable targets emerging from DDR pathways. Further, we discuss how viruses replicate their DNA by hijacking and exploiting the DDR pathways and the potential to target replication stress-associated molecules for the identification of new anticancer molecules.
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Matata, Bashir M., and Maqsood M. Elahi. "Redox Signaling, Oxidative Stress in Cardiovascular Disease –basic Science and Clinical Aspects." In Blood Oxidant Ties: The Evolving Concepts in Myocardial Injury and Cardiovascular Disease, 1–24. BENTHAM SCIENCE PUBLISHERS, 2023. http://dx.doi.org/10.2174/9789815165012123010004.
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The generation of certain species of biomolecules described as reactive oxidant species (ROS e.g., superoxide, O2 -; hydrogen peroxide, H2O2; hydroxyl radicals (OH.)) and reactive nitrogen species (RNS e.g., peroxynitrite, OONO-; nitric oxide, •NO) is a critical step in health and disease . These species play critical roles in cell defences in both animals, and plants. They also perform an important function in the regulation of key cellular signalling pathways such as cell differentiation, proliferation, migration, and apoptosis (commonly described as redox signalling pathways). The imbalance between the levels of ROS and RNS generated to that of antioxidant species may lead to oxidative stress and biomolecular damage, especially in situations where the latter are depleted. Redox biology and oxidative stress are particularly important in ischaemia-reperfusion associated diseases in particular the pathogenesis of cardiovascular disease (CVD). CVD is a major cause of mortality on a global scale, although the exact mechanisms underlying the pathological process are not fully understood. It is believed that ROS play a pivotal role in the progression of CVD. In particular, recent evidence suggests that the development of atherosclerosis is modulated by ROS and influenced by other factors such as inflammatory responses, disturbed blood flow, and arterial wall remodelling. This chapter provides an overview of the pathways of oxidative stress and redox-regulated signalling underlying the genesis and progression of cardiovascular disease.
Conference papers on the topic "Stress signalling pathway"
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Teo, Soo Kng, Kim Parker, and K. H. Chiam. "Viscoelastic Finite-Element Modelling of Cell Deformation in an Optical Stretcher." In ASME 2007 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2007. http://dx.doi.org/10.1115/sbc2007-176085.
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In this paper, we discuss the results arising from using a finite-element model [1] of cell deformation to study the optical stretching [2,3] of normal and malignantly transformed fibroblast cells. The key feature of our model is the use of a constitutive viscoelastic fluid element [4] whose parameters are both spatially and temporally varying so as to mimic the experimentally-observed spatiotemporal heterogeneity of cellular material properties. First, we show that normal fibroblast cells can undergo active cellular response by increasing their cellular viscosity when optically stretched for loading times of between 0.2s and 2.5s. Second, we show that, under similar optical conditions, cells of a smaller radius will experience more stretching compared to cells of a larger radius. This may explain why malignantly transformed cells experience higher strains than normal cells. Third, we compute the extent of the propagation of stress in the cytoplasm, and show that, for malignantly transformed cells, the maximal stress does propagate into the nuclear region whereas for normal cells, the maximal stress does not. We discuss how this may impact the transduction of cancer signalling pathways.
Reports on the topic "Stress signalling pathway"
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Miller, Gad, and Jeffrey F. Harper. Pollen fertility and the role of ROS and Ca signaling in heat stress tolerance. United States Department of Agriculture, January 2013. http://dx.doi.org/10.32747/2013.7598150.bard.
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The long-term goal of this research is to understand how pollen cope with stress, and identify genes that can be manipulated in crop plants to improve reproductive success during heat stress. The specific aims were to: 1) Compare heat stress dependent changes in gene expression between wild type pollen, and mutants in which pollen are heat sensitive (cngc16) or heat tolerant (apx2-1). 2) Compare cngc16 and apx2 mutants for differences in heat-stress triggered changes in ROS, cNMP, and Ca²⁺ transients. 3) Expand a mutant screen for pollen with increased or decreased thermo-tolerance. These aims were designed to provide novel and fundamental advances to our understanding of stress tolerance in pollen reproductive development, and enable research aimed at improving crop plants to be more productive under conditions of heat stress. Background: Each year crop yields are severely impacted by a variety of stress conditions, including heat, cold, drought, hypoxia, and salt. Reproductive development in flowering plants is highly sensitive to hot or cold temperatures, with even a single hot day or cold night sometimes being fatal to reproductive success. In many plants, pollen tube development and fertilization is often the weakest link. Current speculation about global climate change is that most agricultural regions will experience more extreme environmental fluctuations. With the human food supply largely dependent on seeds, it is critical that we consider ways to improve stress tolerance during fertilization. The heat stress response (HSR) has been intensively studied in vegetative tissues, but is poorly understood during reproductive development. A general paradigm is that HS is accompanied by increased production of reactive oxygen species (ROS) and induction of ROS-scavenging enzymes to protect cells from excess oxidative damage. The activation of the HSR has been linked to cytosolic Ca²⁺ signals, and transcriptional and translational responses, including the increased expression of heat shock proteins (HSPs) and antioxidative pathways. The focus of the proposed research was on two mutations, which have been discovered in a collaboration between the Harper and Miller labs, that either increase or decrease reproductive stress tolerance in a model plant, Arabidopsis thaliana (i.e., cngc16--cyclic nucleotide gated channel 16, apx2-1--ascorbate peroxidase 2,). Major conclusions, solutions, achievements. Using RNA-seq technology, the expression profiles of cngc16 and apx2 pollen grains were independently compared to wild type under favourable conditions and following HS. In comparison to a wild type HSR, there were 2,776 differences in the transcriptome response in cngc16 pollen, consistent with a model in which this heat-sensitive mutant fails to enact or maintain a normal wild-type HSR. In a comparison with apx2 pollen, there were 900 differences in the HSR. Some portion of these 900 differences might contribute to an improved HSR in apx2 pollen. Twenty-seven and 42 transcription factor changes, in cngc16 and apx2-1, respectively, were identified that could provide unique contributions to a pollen HSR. While we found that the functional HS-dependent reprogramming of the pollen transcriptome requires specific activity of CNGC16, we identified in apx2 specific activation of flavonol-biosynthesis pathway and auxin signalling that support a role in pollen thermotolerance. Results from this study have identified metabolic pathways and candidate genes of potential use in improving HS tolerance in pollen. Additionally, we developed new FACS-based methodology that can quantify the stress response for individual pollen in a high-throughput fashion. This technology is being adapted for biological screening of crop plant’s pollen to identify novel thermotolerance traits. Implications, both scientific and agricultural. This study has provided a reference data on the pollen HSR from a model plant, and supports a model that the HSR in pollen has many differences compared to vegetative cells. This provides an important foundation for understanding and improving the pollen HSR, and therefor contributes to the long-term goal of improving productivity in crop plants subjected to temperature stress conditions. A specific hypothesis that has emerged from this study is that pollen thermotolerance can be improved by increasing flavonol accumulation before or during a stress response. Efforts to test this hypothesis have been initiated, and if successful have the potential for application with major seed crops such as maize and rice.