Inhibition of Contractile Activity During Postconditioning Enhances Cardioprotection by Restoring Sarcolemmal Dystrophin Through Phosphatidylinositol 3-Kinase
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概要
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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 30min ischemia and 120min 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. (Circ J 2010; 74: 2393-2402)
- 2010-10-25
著者
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Otani Hajime
2ndary Division Of Internal Medicine Kansai Medical University
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Otani Hajime
The Second Department of Internal Medicine, Kansai Medical University
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Sato Daisuke
The Second Department of Internal Medicine, Kansai Medical University
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Iwasaka Toshiji
The Second Department of Internal Medicine, Kansai Medical University
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Okazaki Toru
The second department of internal medicine, Kansai Medical University
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Yamashita Koji
Second Department of Internal Medicine, Division of Cardiology, Kansai Medical University
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Iwasaka T
Second Department Of Internal Medicine Kansai Medical University
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Iwasaka T
Cardiovascular Division Department Of Medicine Ii Kansai Medical University
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Iwasaka Toshiji
The Cardiovascular Center Kansai Medical University
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Sato Daisuke
2ndary Division Of Internal Medicine Kansai Medical University
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Kyoi Shiori
2nd Department Of Internal Medicine Division Of Cardiology Kansai Medical University
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Kyoi Shiori
Cardiovascular Division Department Of Medicine 2 Kansai Medical University
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Kyoi Shiori
Cardiovascular Center Kansai Medical University
-
Okazaki Toru
2ndary Division Of Internal Medicine Kansai Medical University
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Satoh Daisuke
2ndary Division Of Internal Medicine Kansai Medical University
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Ibaraki Toshihiko
Department Of Pharmacology Osaka Medical College
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Yamashita Koji
2ndary Division Of Internal Medicine Kansai Medical University
-
Moriguchi Akira
Cardiovascular Division Department Of Medicine 2 Kansai Medical University
-
Okazaki Toru
Second Department Of Internal Medicine Division Of Cardiology Kansai Medical University
-
Ibaraki Toshihiko
Second Department Of Internal Medicine Kansai Medical University
-
Sato Daisuke
The Second Department Of Internal Medicine Kansai Medical University
-
Kyoi Shiori
The Second Department Of Internal Medicine Kansai Medical University
-
Moriguchi Akira
The Second Department Of Internal Medicine Kansai Medical University
-
Iwasaka Toshiji
The Second Department Of Internal Medicine Kansai Medical University
-
YOSHIOKA Kei
The Second Department of Internal Medicine, Kansai Medical University
-
SHIMAZU Takayuki
The Second Department of Internal Medicine, Kansai Medical University
-
FUJITA Masanori
The Second Department of Internal Medicine, Kansai Medical University
-
Otani Hajime
The Second Department Of Internal Medicine Kansai Medical University
-
Kyoi Shiori
Department Of Cardiology Kansai Medical University
-
Iwasaka Toshiji
Department Of Internal Medicine Cardiovascular Center Kansai Medical University
-
Iwasaka Toshiji
Cardiovascular Division Second Department Of Internal Medicine Kansai Medical University
-
Okazaki Toru
The Second Department Of Internal Medicine Kansai Medical University
-
Iwasaka Toshiji
Department Of Medicine Kansai Medical University Takii Hospital
-
Shimazu Takayuki
The Second Department Of Internal Medicine Kansai Medical University
-
Fujita Masanori
The Second Department Of Internal Medicine Kansai Medical University
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