| Survivin: a novel player in insulin cardioprotection against myocardial ischemia/reperfusion injury. | |
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MedLine Citation:
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PMID: 20801129 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Insulin inhibits ischemia/reperfusion-induced myocardial apoptosis through the activation of a survival signaling cascade including the phosphatidylinositol 3-kinase (PI3K)-Akt pathway. However, the down-stream mechanism of PI3K remains elusive. This study is aimed at investigating whether survivin (SVV) plays a role in the insulin-induced anti-apoptotic effect in the ischemic/reperfused (I/R) hearts, and if so, further determining the signaling mechanism involved. Isolated adult rat hearts were subjected to 30 min regional ischemia followed by reperfusion with or without insulin (10(-7)mol/L) at the onset of reperfusion. Reperfusion with insulin inhibited myocardial apoptosis and reduced infarct size, along with significantly up-regulated myocardial SVV expression (5.9±0.3 Group MI/R+Ins vs. 2.1±0.1 Group MI/R, p<0.05) and increased phosphorylations of mTOR and p70S6K compared with I/R group, which was blocked by pretreatment of PI3K inhibitor LY294002. Rapamycin, a specific mTOR inhibitor, did not alter insulin-induced Akt phosphorylation but significantly inhibited SVV expression (from 6.1±0.3 to 3.0±0.15, p<0.05). Moreover, rapamycin blunted insulin-induced anti-apoptosis in the I/R hearts (8.1±0.4% vs. 16.5±1.8%, p<0.05). To further ascertain the role of SVV in insulin-induced cardioprotection, cardiomyocytes were transfected with adenovirus encoding SVV (gain-of-function) or siRNA targeting SVV (loss-of-function). Overexpression of SVV decreased I/R-induced cardiomyocyte apoptosis in vitro, while siRNA targeting SVV significantly blunted the anti-apoptotic effect of insulin. Taken together, these results suggest a novel role of PI3K/Akt/mTOR/SVV signaling in the cardioprotective effect of insulin. |
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Authors:
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Rui Si; Ling Tao; Hai F Zhang; Qiu J Yu; Rui Zhang; An L Lv; Ning Zhou; Feng Cao; Wen Y Guo; Jun Ren; Hai C Wang; Feng Gao |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-27 |
Journal Detail:
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Title: Journal of molecular and cellular cardiology Volume: 50 ISSN: 1095-8584 ISO Abbreviation: J. Mol. Cell. Cardiol. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0262322 Medline TA: J Mol Cell Cardiol Country: England |
Other Details:
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Languages: eng Pagination: 16-24 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Physiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. |
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| Comments/Corrections | |
Comment In:
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J Mol Cell Cardiol. 2011 Jan;50(1):6-8
[PMID:
20971116
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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