Peroxiredoxin III protects pancreatic ß cells from apoptosis
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 promot...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
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BioScientifica
2010
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| Online Access: | http://hdl.handle.net/20.500.11937/13012 |
| _version_ | 1848748234866950144 |
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| author | Wolf, G. Aumann, N. Michalska, M. Bast, A. Sonnemann, J. Beck, J. Lendeckel, U. Newsholme, Philip Walther, R. |
| author_facet | Wolf, G. Aumann, N. Michalska, M. Bast, A. Sonnemann, J. Beck, J. Lendeckel, U. Newsholme, Philip Walther, R. |
| author_sort | Wolf, G. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T07:01:49Z |
| format | Journal Article |
| id | curtin-20.500.11937-13012 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:01:49Z |
| publishDate | 2010 |
| publisher | BioScientifica |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-130122017-09-13T15:02:12Z Peroxiredoxin III protects pancreatic ß cells from apoptosis Wolf, G. Aumann, N. Michalska, M. Bast, A. Sonnemann, J. Beck, J. Lendeckel, U. Newsholme, Philip Walther, R. 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. 2010 Journal Article http://hdl.handle.net/20.500.11937/13012 10.1677/JOE-09-0455 BioScientifica unknown |
| spellingShingle | Wolf, G. Aumann, N. Michalska, M. Bast, A. Sonnemann, J. Beck, J. Lendeckel, U. Newsholme, Philip Walther, R. Peroxiredoxin III protects pancreatic ß cells from apoptosis |
| title | Peroxiredoxin III protects pancreatic ß cells from apoptosis |
| title_full | Peroxiredoxin III protects pancreatic ß cells from apoptosis |
| title_fullStr | Peroxiredoxin III protects pancreatic ß cells from apoptosis |
| title_full_unstemmed | Peroxiredoxin III protects pancreatic ß cells from apoptosis |
| title_short | Peroxiredoxin III protects pancreatic ß cells from apoptosis |
| title_sort | peroxiredoxin iii protects pancreatic ß cells from apoptosis |
| url | http://hdl.handle.net/20.500.11937/13012 |