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.
Artigo
em Inglês
| WPRIM
| ID: wpr-65170
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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fosforilação
/
Traumatismo por Reperfusão Miocárdica
/
Distribuição Aleatória
/
Ratos Sprague-Dawley
/
Organismos Livres de Patógenos Específicos
/
Precondicionamento Isquêmico Miocárdico
/
Quinase 3 da Glicogênio Sintase
/
Proteínas Proto-Oncogênicas c-akt
/
Fosfatidilinositol 3-Quinase
/
Gadolínio
Limite:
Animais
Idioma:
Inglês
Revista:
Journal of Veterinary Science
Ano de publicação:
2012
Tipo de documento:
Artigo
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