Abstract
Ischemic heart disease is a leading cause of mortality and morbidity worldwide. We previously demonstrated that acacetin protects against myocardial ischemia reperfusion injury in rats, although the underlying mechanism remains to be elucidated. In the present study, we investigated the effects of acacetin on autophagy during hypoxia/reoxygenation (H/R) injury by exposing H9c2 myocardial cells to H/R with or without acacetin pretreatment during hypoxia. Our results show that acacetin significantly increased cell viability in a dose-dependent manner, enhanced antioxidant capacity, and suppressed protein apoptosis of rat cardiomyocytes H9c2 cells following H/R injury. In addition, lentiviral infection of H9c2 cardiomyocytes revealed that acacetin pretreatment significantly enhanced the fluorescence intensity of autophagy proteins Beclin 1, LC3-II, and p62. These results indicate that acacetin protected H9c2 cardiomyocytes from H/R damage by enhancing autophagy. Moreover, we found that application of acacetin increased activation of the PI3K/Akt signaling pathway, whereas cotreatment with the PI3K inhibitor LY294002 reversed the inhibition of apoptosis and autophagy induced by acacetin. In conclusion, acacetin mitigated H/R injury by promoting autophagy through activating the PI3K/Akt/mTOR signaling pathway.
Highlights
Ischemic heart disease is a leading cause of mortality and morbidity worldwide [1]
The objective of the current study was to determine whether the beneficial effect of acacetin on cardiomyocytes exposed to H/R injury involves autophagy as a protective mechanism
We showed that acacetin preconditioning suppressed myocardial cell apoptosis of rat cardiomyocytes following damage caused by H/R injury
Summary
Ischemic heart disease is a leading cause of mortality and morbidity worldwide [1]. Reperfusion therapy is regarded as the most effective measure to save ischemic myocardium [2]. Myocardial ischemic-reperfusion therapy may induce ultrastructural damage and functional impairment of cardiomyocytes, which aggravates ischemic myocardium injury [3,4,5]. Reports describing therapeutic interventions and prognosis of myocardial injury have recently increased, available therapies still induce ultrastructural damage and functional impairments in cardiomyocytes [6]. Many researchers have discussed problems with optimizing myocardial injury therapy, but potential mechanisms and drug targets of myocardial injury remain to be elucidated. Novel pharmacological or other effective targets are urgently needed to protect against myocardial hypoxia-reoxygenation (H/R) injury
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