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.
Keywords: autophagy; cardiac fibroblasts; endoplasmic reticulum; hydrogen sulfide; lysosome.