Peroxiredoxin III protects pancreatic ß cells from apoptosis
|dc.identifier.citation||Wolf, G. and Aumann, N. and Michalska, M. and Bast, A. and Sonnemann, J. and Beck, J. and Lendeckel, U. et al. 2010. Peroxiredoxin III protects pancreatic ß cells from apoptosis. Journal of Endocrinology. 207 (2): pp. 163-175.|
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.
|dc.title||Peroxiredoxin III protects pancreatic ß cells from apoptosis|
|dcterms.source.title||Journal of Endocrinology|
|curtin.department||School of Biomedical Sciences|
|curtin.accessStatus||Open access via publisher|
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