Peroxiredoxin III protects pancreatic ß cells from apoptosis
MetadataShow full item record
Type 1 diabetes mellitus is characterized by a progressive autoimmune destruction of insulin-producing ß cells. Macrophages and T lymphocytes release cytokines, which induce the synthesis of oxygen and nitrogen radicals in the pancreatic islets. The resulting cellular and mitochondrial damage promotes ß cell death. ß cells are very sensitive to the autoimmune free radical-dependent attack due to their low content of antioxidant enzymes such as glutathione peroxidase and catalase. A focal point of ß cell protection should be the control of the mitochondrial redox status, which will result in the preservation of metabolic stimulus-secretion coupling. For this reason, there is a considerable interest in the mitochondrial peroxiredoxin III (PRX III), a thioredoxin-dependent peroxide reductase, which was shown to be able to protect against both oxidative and nitrosative stress. Using the Tet-On-system, we generated stably transfected rat insulinoma cells over- or under-expressing PRX III in a doxycyclin-dependent manner to analyze the effect of increased or decreased amounts of cellular PRX III, following treatment with several stressors. We provide evidence that PRX III protects pancreatic ß cells from cell stress induced by accumulation of hydrogen peroxide, or the induction of inducible nitric oxide synthase or caspase-9 and -3 by pro-inflammatory cytokines or streptozotocin. Basal insulin secretion was markedly decreased in cells expressing lower levels of PRX III. We suggest PRX III may be a suitable target for promoting deceleration or even prevention of stress-associated apoptosis in pancreatic ß cells and the manifestation of insulin-dependent diabetes mellitus. © 2010 Society for Endocrinology.
Showing items related by title, author, creator and subject.
Arachidonic acid actions on functional integrity and attenuation of the negative effects of palmitic acid in a clonal pancreatic ß-cell lineKeane, D.; Takahashi, H.; Dhayal, S.; Morgan, N.; Curi, R.; Newsholme, Philip (2011)Chronic exposure of pancreatic β-cells to saturated non-esterified fatty acids can lead to inhibition of insulin secretion and apoptosis. Several previous studies have demonstrated that saturated fatty acids such as PA ...
The regulatory roles of NADPH oxidase, intra- and extra-cellular HSP70 in pancreatic islet function, dysfunction and diabetesKrause, M.; Bock, P.; Takahashi, H.; Homem De Bittencourt, P.; Newsholme, Philip (2015)The 70 kDa heat-shock protein (HSP70) family is important for a dynamic range of cellular processes that include protection against cell stress, modulation of cell signalling, gene expression, protein synthesis, protein ...
Cruzat, Vinicius; Keane, Kevin; Scheinpflug, A.; Cordeiro, R.; Soares, M.; Newsholme, Philip (2015)Obesity-associated diabetes and concomitant inflammation may compromise pancreatic β-cell integrity and function. l-glutamine and l-alanine are potent insulin secretagogues, with antioxidant and cytoprotective properties. ...