Activation of Akt/protein kinase B mediates the protective effects of mechanical stretching against myocardial ischemia-reperfusion injury.
10.4142/jvs.2012.13.3.235
- Author:
Chan Hyung KIM
1
;
Jia HAO
;
Hee Yul AHN
;
Si Wook KIM
Author Information
1. Department of Public Health, Chengdu Medical College, Chengdu, Sichuan 610083, China.
- Publication Type:Original Article ; In Vitro ; Research Support, Non-U.S. Gov't
- Keywords:
Akt/protein kinase B;
cardioprotection;
ischemia-reperfusion injury;
mechanical stretching
- MeSH:
Androstadienes/pharmacology;
Animals;
Gadolinium/pharmacology;
Glycogen Synthase Kinase 3/*metabolism;
Indoles/pharmacology;
*Ischemic Preconditioning, Myocardial;
Lithium/pharmacology;
Male;
Maleimides/pharmacology;
Myocardial Reperfusion Injury/enzymology/physiopathology/*prevention & control;
Phosphatidylinositol 3-Kinase/*antagonists & inhibitors/metabolism;
Phosphorylation;
Proto-Oncogene Proteins c-akt/*metabolism;
Random Allocation;
Rats;
Rats, Sprague-Dawley;
Specific Pathogen-Free Organisms
- From:Journal of Veterinary Science
2012;13(3):235-244
- CountryRepublic of Korea
- Language:English
-
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.
