Hydrogen Sulfide Protects Human Cardiac Fibroblasts Against H(2)O(2)-induced Injury Through Regulating Autophagy-Related Proteins

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 (H(2)O(2)) exposure. Because hydrogen sulfide (H(2)S) regulates reactive oxygen species (ROS) and apoptosis, we hypothesize that H(2)S may have a cardioprotective function. To examine our hypothesis, we investigated the regulation of autophagy by the H(2)S 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 H(2)O(2). In the present study, we found that the apoptosis and autophagy were induced along with ER stress by H(2)O(2) in the primary cultured HCF-av cells. In contrast, H(2)S suppressed HCF-av cell apoptosis and autophagic flux, in part directly by inhibiting ROS production and preserving mitochondrial functions.