Exogenous hydrogen sulfide ameliorates high glucose-induced myocardial injury & inflammation via the CIRP-MAPK signaling pathway in H9c2 cardiac cells.

AIMS

Hydrogen sulfide (HS) is a novel signaling molecule with potent cytoprotective actions. In this study, we hypothesize that exogenous HS may protect cardiac cells against high glucose (HG)-induced myocardial injury and inflammation with the involvement of the CIRP-MAPK signaling pathway.

MAIN METHODS

H9c2 cardiac cells cultured under HG conditions were transfected with siRNA and different inhibitor for detecting the effects of sodium hydrogen sulfide (NaHS) (a HS donor) on cell biological processes. The cardiac cell viability and LDH activity were determined by CCK-8 and LDH kit. ELISA was employed to measure the levels of inflammatory factors, while 2',7'-dichlorofluorescein diacetate (DCFH-DA) to evaluate reactive oxygen species (ROS). Mitochondrial membrane potential (MMP) was identified by rhodamine 123 staining. TUNEL staining and Hoechst 33258 staining were employed to observe cardiac cell apoptosis. Besides, we determined the expression of CIRP-MAPK signaling pathway- and apoptosis-related factors by protein immunoblot analysis.

KEY FINDINGS

HG culturing induced toxicity, LDH, higher level of inflammatory factors, ROS, MMP, and apoptosis in cardiac cells, attenuated the viability of cardiac cells, and activated the CIRP-MAPK signaling pathway. Notably, CIRP silencing aggravated the above condition. HS or blockade of the MAPK signaling pathway reversed the above conditions induced by HG.

SIGNIFICANCE

The present study provides evidence for the protective effect of exogenous HS on HG-induced myocardial injury and inflammation in H9c2 cardiac cells and suggests that the activation of CIRP-MAPK signaling pathway might be one of the mechanisms underlying the protective effect of HS.