| Reg2 protects mouse insulinoma cells from streptozotocin-induced mitochondrial disruption and apoptosis. | |
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MedLine Citation:
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PMID: 20919961 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We reported previously that pancreas-specific ablation of IGF-I in mice induced an increased expression of regenerating family proteins Reg2 and Reg3β in the pancreas and protected them from streptozotocin (Stz)-induced β-cell damage. We, therefore, assessed the effect of ectopically introduced Reg2 on Stz-induced apoptosis in MIN6 mouse insulinoma cells and report here that Reg2 protects MIN6 cells from Stz-induced apoptosis by attenuating its ability to disrupt mitochondrial membrane integrity, activate caspase-3 and promote poly-ADP ribose polymerase cleavage, and induce apoptosis. These changes correlated with suppression of c-jun N-terminal kinase (JNK) phosphorylation by Stz. Reg2 inhibited Stz-induced proapoptotic events as well as the inactivation of JNK. Inclusion of chemical inhibitor of JNK to Reg2 expressing cells rendered them sensitive to Stz. These data demonstrate that Reg2 protects insulin-producing cells against Stz-induced apoptosis by interfering with its cytotoxic signaling upstream of the intrinsic proapoptotic events by preventing its ability to inactivate JNK. |
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Authors:
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Lu Liu; Jun-Li Liu; Coimbatore B Srikant |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Growth factors (Chur, Switzerland) Volume: 28 ISSN: 1029-2292 ISO Abbreviation: Growth Factors Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-05 Completed Date: 2011-01-31 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9000468 Medline TA: Growth Factors Country: England |
Other Details:
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Languages: eng Pagination: 370-8 Citation Subset: IM |
Affiliation:
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Fraser Laboratories, McGill University Health Centre and Royal Victoria Hospital, Montreal, Quebec, Canada H3A 1A1. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis* Caspase 3 / metabolism Cell Line, Tumor Diabetes Mellitus, Experimental / genetics*, pathology Insulin-Secreting Cells / drug effects, metabolism*, pathology JNK Mitogen-Activated Protein Kinases / metabolism Mice Mitochondria / drug effects, pathology Phosphorylation Poly(ADP-ribose) Polymerases / metabolism Proteins / genetics, metabolism* Streptozocin / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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MOP-84389//Medical Research Council |
| Chemical | |
Reg. No./Substance:
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0/Pap protein, mouse; 0/Proteins; 18883-66-4/Streptozocin; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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