Oxidative stress may play a crucial role in cardiac and vascular abnormalities in different types of cardiovascular diseases. In the present study, we explored the mechanism underlying oxidative stress-mediated cardiomyocyte apoptosis with a focus on the Akt-p53 signaling pathway. In vitro, cardiomyocyte was cultured with different concentrations of hydrogen peroxide. Then, cardiomyocyte viability, apoptosis rate and signaling pathway were analyzed through ELISA, immunofluorescence, qPCR and western blots. The results indicated that oxidative stress caused cardiomyocyte apoptosis in a dose-dependent manner. Mechanistically, oxidative stress inhibited cardiomyocyte glucose metabolism and promoted lactic acid accumulation. Besides, oxidative stress triggered calcium overload in cardiomyocyte. Finally, we found that oxidative stress inhibited the activity of Akt pathway while activated p53 signaling pathway. Genetic knockdown of p53 abolished oxidative stress-mediated cardiomyocyte injury and death through regulating the expressions and activities of caspase-3 and Bax. Altogether, our results illustrate that oxidative stress is associated with cardiomyocyte apoptosis through a mechanism involving dysregulated Akt/p53 signaling pathway.
Keywords: Akt; Oxidative stress; cardiomyocyte; p53.