| Modulation of Bcl-2-related protein expression in pancreatic beta cells by pro-inflammatory cytokines and its dependence on the antioxidative defense status. | |
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MedLine Citation:
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PMID: 20933054 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Pro-inflammatory cytokines are key mediators in the selective and progressive destruction of insulin-producing beta cells during type 1 diabetes development. However, the mechanisms of cytokine-induced beta cell apoptosis are not fully understood. This study demonstrates that pro-inflammatory cytokines strongly modified the expression of the anti-apoptotic protein Bcl-2 and the pro-apoptotic BH3-only proteins Bad, Bim, and Bid in primary rat islets and insulin-producing RINm5F cells. Overexpression of mitochondrially located catalase (MitoCatalase) specifically increased basal Bcl-2 and decreased basal Bax expression, suppressed cytokine-mediated reduction of Bcl-2, and thereby prevented the release of cytochrome c, Smac/DIABLO and the activation of caspase-9 and -3. Thus, cytokine-mediated decrease of Bcl-2 expression and the sequentially changed Bax/Bcl-2 ratio are responsible for the release of pro-apoptotic mitochondrial factors, activation of caspase-9, and ultimately caspase-3. These results indicate that activation of the intrinsic/mitochondrial apoptosis pathway is essential for cytokine-induced beta cell death and the mitochondrial generation of reactive oxygen species, in particular mitochondrial hydrogen peroxide, differentially regulates the Bax/Bcl-2 ratio. |
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Authors:
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Ilir Mehmeti; Sigurd Lenzen; Stephan Lortz |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-07 |
Journal Detail:
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Title: Molecular and cellular endocrinology Volume: 332 ISSN: 1872-8057 ISO Abbreviation: Mol. Cell. Endocrinol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7500844 Medline TA: Mol Cell Endocrinol Country: Ireland |
Other Details:
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Languages: eng Pagination: 88-96 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Institute of Clinical Biochemistry, Hannover Medical School, 30623 Hannover, Germany. |
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