Document Detail


Inhibition of contractile activity during postconditioning enhances cardioprotection by restoring sarcolemmal dystrophin through phosphatidylinositol 3-kinase.
MedLine Citation:
PMID:  20877127     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Although ischemic postconditioning (IPost) confers cardioprotection by protecting the mitochondria though the activation of phosphatidylinositol 3-kinase (PI3K), a potential drawback of IPost is impairment of aerobic ATP generation during reperfusion by repeated ischemia. This decrease in ATP might inhibit the restoration of sarcolemmal dystrophin, which is translocated during ischemia, and render cardiomyocytes susceptible to contraction-induced oncosis.
METHODS AND RESULTS: Isolated rat hearts were subjected to 30 min ischemia and 120 min reperfusion. IPost induced by 20 cycles of 10-s reperfusion and 10-s ischemia enhanced the activation of PI3K as evidenced by the increased phosphorylation of Akt, but had no effect on myocardial ATP, restoration of sarcolemmal dystrophin, or cardiomyocyte oncosis during IPost. Administration of the contractile blocker, 2,3-butanedione monoxim (BDM), during IPost increased myocardial ATP and facilitated the redistribution of dystrophin to the sarcolemma. This led to reduced cardiomyocyte oncosis and infarct size, and improved the left ventricular function. The anti-oncotic effect of BDM occurred without changing the anti-apoptotic effect of IPost. The PI3K inhibitor, LY294002, prevented the phosphorylation of Akt, decreased the recovery of ATP and restoration of sarcolemmal dystrophin, and blocked the anti-oncotic and anti-apoptotic effects of IPost.
CONCLUSIONS: These results suggest that the inhibition of contractile activity during IPost prevents cardiomyocyte oncosis and enhances cardioprotection through PI3K-dependent restoration of sarcolemmal dystrophin.
Authors:
Akira Moriguchi; Hajime Otani; Kei Yoshioka; Takayuki Shimazu; Masanori Fujita; Toru Okazaki; Daisuke Sato; Shiori Kyoi; Toshiji Iwasaka
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-18
Journal Detail:
Title:  Circulation journal : official journal of the Japanese Circulation Society     Volume:  74     ISSN:  1347-4820     ISO Abbreviation:  Circ. J.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-29     Completed Date:  2010-11-30     Revised Date:  2011-02-18    
Medline Journal Info:
Nlm Unique ID:  101137683     Medline TA:  Circ J     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  2393-402     Citation Subset:  IM    
Affiliation:
The Second Department of Internal Medicine, Kansai Medical University, Moriguchi, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Animals
Apoptosis / drug effects
Chromones / pharmacology
Cytoprotection
Diacetyl / analogs & derivatives*,  pharmacology
Dystrophin / metabolism*
Enzyme Activation
Ischemic Postconditioning*
Male
Morpholines / pharmacology
Myocardial Contraction / drug effects*
Myocardial Infarction / enzymology,  pathology,  physiopathology,  prevention & control*
Myocardial Reperfusion Injury / enzymology,  pathology,  physiopathology,  prevention & control*
Myocardium / enzymology*,  pathology
Perfusion
Phosphatidylinositol 3-Kinases / antagonists & inhibitors,  metabolism*
Phosphorylation
Protein Kinase Inhibitors / pharmacology
Protein Transport
Proto-Oncogene Proteins c-akt / metabolism
Rats
Rats, Sprague-Dawley
Sarcolemma / enzymology*
Signal Transduction / drug effects
Time Factors
Ventricular Function, Left / drug effects
Chemical
Reg. No./Substance:
0/Chromones; 0/Dystrophin; 0/Morpholines; 0/Protein Kinase Inhibitors; 154447-36-6/2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; 431-03-8/Diacetyl; 56-65-5/Adenosine Triphosphate; 57-71-6/diacetylmonoxime; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt
Comments/Corrections
Comment In:
Circ J. 2010 Nov;74(11):2295-6   [PMID:  20962422 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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