L-Carnitine Attenuates Cardiac Dysfunction by Ischemic Insults through Akt Signaling Pathway.
Toxicol Sci. 2017 Sep 9. Epub 2017 Sep 9. PMID: 28973678
We aim to investigate the cardioprotective effects of L-carnitine on cardiac function during ischemia and reperfusion (I/R) and contractile function of single cardiomyocyte. C57BL/6J mice were randomly assigned to 5 groups: sham group; vehicle group, L-carnitine preconditioning group (LC), LC preconditioning + LY294002 (a PI3K/Akt signaling pathway inhibitor) group (LC + LY), and LY294002 group (LY). The sham group was exposed to the open heart operation but not ischemia/reperfusion, the other groups received 45 min ischemia/48 hrs reperfusion. At the end of reperfusion, echocardiography was performed on every mouse. In order to determine whether LC's cardioprotection could act directly at the level of cardiomyocytes, we also tested its effects on isolated cardiomyocytes under hypoxia condition. The expressions of p-PI3K, PI3K, Akt, p-Akt, Bax and Bcl-2 proteins was detected by immunoblotting. The results showed that LC preconditioning remarkably improved cardiac function after I/R, but the cardioprotective effect of LC was significantly weakened after the application of LY294002. We also found that LC could directly improve the contractile function of cardiomyocytes under hypoxia condition. The immunoblotting results showed that LC administration restrained myocardial apoptosis as evidenced by decreasing the level of Bax expression, increasing the levels of phosphorylation of Akt, PI3K andBcl-2 protein expression, but these were blocked by LYC94002. Thus, the cardioprotective effects of LC against myocardial ischemic damage and its effect on single cardiomyocyte under hypoxia may be associated with the PI3K/Akt signaling pathway.