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Activation of Akt/protein kinase B mediates the protective effects of mechanical stretching against myocardial ischemia-reperfusion injury.
J Vet Sci. 2012 Sep; 13(3):235-44.JV

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+Show Affiliations

Department of Pharmacology, College of Medicine, Chungbuk National University, Cheongju 361-763, Korea. kch@chungbuk.ac.krNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23000580

Citation

Kim, Chan-Hyung, et al. "Activation of Akt/protein Kinase B Mediates the Protective Effects of Mechanical Stretching Against Myocardial Ischemia-reperfusion Injury." Journal of Veterinary Science, vol. 13, no. 3, 2012, pp. 235-44.
Kim CH, Hao J, Ahn HY, et al. Activation of Akt/protein kinase B mediates the protective effects of mechanical stretching against myocardial ischemia-reperfusion injury. J Vet Sci. 2012;13(3):235-44.
Kim, C. H., Hao, J., Ahn, H. Y., & Kim, S. W. (2012). Activation of Akt/protein kinase B mediates the protective effects of mechanical stretching against myocardial ischemia-reperfusion injury. Journal of Veterinary Science, 13(3), 235-44.
Kim CH, et al. Activation of Akt/protein Kinase B Mediates the Protective Effects of Mechanical Stretching Against Myocardial Ischemia-reperfusion Injury. J Vet Sci. 2012;13(3):235-44. PubMed PMID: 23000580.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of Akt/protein kinase B mediates the protective effects of mechanical stretching against myocardial ischemia-reperfusion injury. AU - Kim,Chan-Hyung, AU - Hao,Jia, AU - Ahn,Hee-Yul, AU - Kim,Si Wook, PY - 2012/9/25/entrez PY - 2012/9/25/pubmed PY - 2013/2/21/medline SP - 235 EP - 44 JF - Journal of veterinary science JO - J Vet Sci VL - 13 IS - 3 N2 - 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. SN - 1976-555X UR - https://www.unboundmedicine.com/medline/citation/23000580/Activation_of_Akt/protein_kinase_B_mediates_the_protective_effects_of_mechanical_stretching_against_myocardial_ischemia_reperfusion_injury_ L2 - https://www.vetsci.org/DOIx.php?id=10.4142/jvs.2012.13.3.235 DB - PRIME DP - Unbound Medicine ER -