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Peroxiredoxin III protects pancreatic {beta} cells from apoptosis.
MedLine Citation:
PMID:  20807727     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Type 1 diabetes mellitus is characterized by a progressive autoimmune destruction of insulin-producing β 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 β cell death. β 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 β 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 β 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 β cells and the manifestation of insulin-dependent diabetes mellitus.
Authors:
Gabriele Wolf; Nicole Aumann; Marta Michalska; Antje Bast; Jürgen Sonnemann; James F Beck; Uwe Lendeckel; Philip Newsholme; Reinhard Walther
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-31
Journal Detail:
Title:  The Journal of endocrinology     Volume:  207     ISSN:  1479-6805     ISO Abbreviation:  J. Endocrinol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  163-75     Citation Subset:  IM    
Affiliation:
Department of Medical Biochemistry and Molecular Biology, University of Greifswald, Klinikum, Sauerbruchstrasse, D-17487 Greifswald, Germany.
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