Peroxiredoxin III protects pancreatic {beta} cells from apoptosis.

G. Wolf, N. Aumann, M. Michalska, A. Bast, J. Sonnemann, J.F. Beck, U. Lendeckel, P. Newsholme, R. Walther

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    Abstract

    Aims/hypothesis Type 1 diabetes mellitus is characterized by a progressive autoimmune destruction of insulin producing beta 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 beta cell death. Beta 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 beta cell protection should be the control of the mitochondrial redox status which will result in preservation of metabolic stimulus-secretion coupling. For this reason, there is a considerable interest in the mitochondrial peroxiredoxin III, a thioredoxin-dependent peroxide reductase, which was shown to be able to protect against both oxidative and nitrosative stress. Methods Using the Tet-On-system we generated stably transfected rat insulinoma cells over- or under-expressing peroxiredoxin III in a doxycyclin-dependent manner to analyze the effect of increased or decreased amounts of cellular peroxiredoxin III, following treatment with several stressors. Results We provide evidence that peroxiredoxin III protects pancreatic beta cells from cell stress induced by accumulation of hydrogen peroxide, or the induction of iNOS or caspases 9 and 3 by pro-inflammatory cytokines or streptozotocin. Basal insulin secretion was markedly decreased in cells expressing lower levels of peroxiredoxin III. Conclusions/interpretation We suggest Peroxiredoxin III may be a suitable target for promoting deceleration or even prevention of stress associated apoptosis in pancreatic beta cells and the manifestation of insulin dependent diabetes mellitus.
    Original languageEnglish
    Pages (from-to)163-175
    JournalJournal of Endocrinology
    Volume207
    Issue number2
    DOIs
    Publication statusPublished - 1 Jan 2010

    Cite this

    Wolf, G., Aumann, N., Michalska, M., Bast, A., Sonnemann, J., Beck, J. F., Lendeckel, U., Newsholme, P., & Walther, R. (2010). Peroxiredoxin III protects pancreatic {beta} cells from apoptosis. Journal of Endocrinology, 207(2), 163-175. https://doi.org/10.1677/JOE-09-0455