Hydrogen Sulfide Protects Human Cardiac Fibroblasts Against H₂O₂-induced Injury Through Regulating Autophagy-Related...

Autophagy, an intracellular bulk degradation process of proteins and organelles, can be induced by myocardial ischemia in the heart. However, the causative role of autophagy in the survival of human cardiac fibroblasts and the underlying mechanisms are incompletely understood. Oxidative stress can induce autophagy in cultured cells upon hydrogen peroxide (H₂O₂) exposure. Because hydrogen sulfide (H₂S) regulates reactive oxygen species (ROS) and apoptosis, we hypothesize that H₂S may have a cardioprotective function. To examine our hypothesis, we investigated the regulation of autophagy by the H₂S donor sodium hydrosulfide (NaHS), using a cell model of human cardiac fibroblasts from adult ventricles (HCF-av) that suffered from endoplasmic reticulum (ER) stress by H₂O₂. In the present study, we found that the apoptosis and autophagy were induced along with ER stress by H₂O₂ in the primary cultured HCF-av cells. In contrast, H₂S suppressed HCF-av cell apoptosis and autophagic flux, in part directly by inhibiting ROS production and preserving mitochondrial functions.