Activation of Akt/protein kinase B mediates the protective effects of mechanical stretching against myocardial ischemia-reperfusion injury.

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 postischemic cardiac function compared to the control group. Phosphorylation of Akt and its downstream substrate, GSK-3β, was increased by mechanical stretching and completely blocked by wortmannin, a PI3K inhibitor. Treatment with lithium or SB216763 (GSK-3β 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-3β. 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.

• Authors: Chan-Hyung Kim, Jia Hao, Hee-Yul Ahn, Si Wook Kim
• Journal: Journal of veterinary science (J Vet Sci) Vol. 13 Issue 3 Pg. 235-44 (Sep 2012) ISSN: 1976-555X [Electronic] Korea (South)
• PMID: 23000580 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Androstadienes
• Indoles
• Maleimides
• Phosphoinositide-3 Kinase Inhibitors
• SB 216763
• Lithium
• Gadolinium
• Phosphatidylinositol 3-Kinase
• Glycogen Synthase Kinase 3 beta
• Gsk3b protein, rat
• Proto-Oncogene Proteins c-akt
• Glycogen Synthase Kinase 3
• Wortmannin

Topics

• Androstadienes (pharmacology)
• Animals
• Gadolinium (pharmacology)
• Glycogen Synthase Kinase 3 (metabolism)
• Glycogen Synthase Kinase 3 beta
• In Vitro Techniques
• Indoles (pharmacology)
• Ischemic Preconditioning, Myocardial
• Lithium (pharmacology)
• Male
• Maleimides (pharmacology)
• Myocardial Reperfusion Injury (enzymology, physiopathology, prevention & control)
• Phosphatidylinositol 3-Kinase (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Specific Pathogen-Free Organisms
• Wortmannin