Hydrogen sulfide attenuates high glucose-induced cardiotoxicity via enhancing autophagy activity in human AC 16 cardiac cells

Diabetic cardiomyopathy (DCM) is a major cause of mortality and morbidity in complications of diabetes mellitus (DM) and dysregulated autophagy is proven to contribute to the physiological and pathological processes of DCM. Recent studies have shown that hydrogen sulide (H2S) generation is reduced in diabetic mouse hearts and exogenous H2S has cardioprotective effects in variety of cardiovascular diseases. Thus, the purpose of present study was to investigate whether exogenous H2S prevents high glucose (HG)-induced cardiotoxicity through regulating autophagy in human myocardial cells (AC16 cells). We noted that treatment with different concentration of HG significantly induces cardiotoxicity, leading to decrease in the viability of AC16 cells and increase in apoptotic cells. In addition, HG treatment also increased the activity of caspase-3 and the expression of Bax (pro-apoptocic protein), and decreased the expression of Bcl-2 (anti-apoptocic protein) in AC16 cells. However, these all injuries were markedly attenuated by pre-treatment with NaHS (a donor of H2S). These results suggest that exogenous H2S exerts a protective role in HG-induced cardiomyocyte damages. Furthermore, HG also down-regulated the LC3 II/I ratio and suppress the expression levels of Beclin1, while the expression levels of P62 is enhanced by HG treatment, which indicates the downregulation of autophagy in HG-treated AC16 cells. Notably, pre-treatment with NaHS for 30 min markedly revises HG-caused the inhibition of autophagy in AC16 cells. Furthermore, we found that Bafilomycin A1 (Baf, an autophagy inhibitor) attenuates the protective effects of H2S on HG-induced cytotoxicity and apoptosis in AC16 cells. Taken together, these studies demonstrate that H2S attenuates HG-induced cardiotoxicity through enhancing autophagy.