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  • Title: The cystathionine γ-lyase/hydrogen sulfide pathway mediates the trimetazidine-induced protection of H9c2 cells against hypoxia/reoxygenation-induced apoptosis and oxidative stress.
    Author: Zheng W, Liu C.
    Journal: Anatol J Cardiol; 2019 Sep; 22(3):102-111. PubMed ID: 31475956.
    Abstract:
    OBJECTIVE: Trimetazidine is a piperazine-derived metabolic agent. It exerts cardioprotective effects against myocardial ischemia/reperfusion (I/R) injury. In addition, studies confirm that the cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway serves a beneficent role in attenuating myocardial I/R injury. However, the underlying role of the CSE/H2S pathway in the trimetazidine-induced protection against myocardial I/R injury remains elusive. Therefore, this study investigated whether trimetazidine ameliorates hypoxia/reoxygenation (H/R)-induced H9c2 cardiomyocyte injuries in an in vitro cell model of myocardial I/R injury, by enhancing the CSE/H2S pathway. METHODS: The H9c2 cell viability was determined with a cell counting Kit-8. RESULTS: Trimetazidine significantly increased the cell viability and decreased lactate dehydrogenase (LDH) release in H/R-treated H9c2 cells. Additionally, trimetazidine increased the H2S levels and the CSE mRNA and protein levels, promoting the CSE/H2S pathway under H/R conditions. The inhibition of the CSE/H2S pathway, induced by transfection with specific siRNA against human CSE (si-CSE), eliminated the trimetazidine-induced upregulation of cell viability, downregulation of LDH release, increase of caspase-3 activity and apoptosis regulator BAX expression, and the decrease of apoptosis regulator Bcl-2 expression, which suggests involvement of the CSE/H2S pathway in trimetazidine-induced cardioprotection. Furthermore, trimetazidine mitigated the H/R-induced increase in reactive oxygen species production and NADPH oxidase 2 expression, and decrease in superoxide dismutase activity and glutathione level, in H9c2 cells. These effects were also reversed by si-CSE. CONCLUSION: This study revealed that the CSE/H2S pathway mediates the trimetazidine-induced protection of H9c2 cardiomyocytes against H/R-induced damage by inhibiting apoptosis and oxidative stress.
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