Activation of Akt/protein kinase B mediates the protective effects of mechanical stretching against myocardial ischemia-reperfusion injury
Journal of Veterinary Science
; : 235-244, 2012.
Article
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| ID: wpr-65170
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ABSTRACT
Akt/protein kinase B is a well-known cell survival factor and activated by many stimuli including mechanical stretching. Therefore, we evaluated the cardioprotective effect of a brief mechanical stretching of rat hearts and determined whether activation of Akt through phosphatidylinositol 3-kinase (PI3K) is involved in stretch-induced cardioprotection (SIC). Stretch preconditioning reduced infarct size and improved post-ischemic cardiac function compared to the control group. Phosphorylation of Akt and its downstream substrate, GSK-3beta, was increased by mechanical stretching and completely blocked by wortmannin, a PI3K inhibitor. Treatment with lithium or SB216763 (GSK-3beta inhibitors) before ischemia induction mimicked the protective effects of SIC on rat heart. Gadolinium (Gd3+), a blocker of stretch-activated ion channels (SACs), inhibited the stretch-induced phosphorylation of Akt and GSK-3beta. Furthermore, SIC was abrogated by wortmannin and Gd3+. In vivo stretching induced by an aorto-caval shunt increased Akt phosphorylation and reduced myocardial infarction; these effects were diminished by wortmannin and Gd3+ pretreatment. Our results showed that mechanical stretching can provide cardioprotection against ischemia-reperfusion injury. Additionally, the activation of Akt, which might be regulated by SACs and the PI3K pathway, plays an important role in SIC.
Texte intégral:
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Indice:
WPRIM
Sujet Principal:
Phosphorylation
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Lésion de reperfusion myocardique
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Répartition aléatoire
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Rat Sprague-Dawley
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Organismes exempts d'organismes pathogènes spécifiques
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Préconditionnement ischémique myocardique
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Glycogen Synthase Kinase 3
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Protéines proto-oncogènes c-akt
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Phosphatidylinositol 3-kinase
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Gadolinium
Limites du sujet:
Animals
langue:
En
Texte intégral:
Journal of Veterinary Science
Année:
2012
Type:
Article