H₂S Protects against Cardiac Cell Hypertrophy through Regulation of Selenoproteins

Cardiac hypertrophy is defined as the enlargement of the cardiac myocytes, leading to improper nourishment and oxygen supply due to the increased functional demand. This increased stress on the cardiac system commonly leads to myocardial infarction, contributing to 85% of all cardiac-related deaths. Cystathionine gamma-lyase- (CSE-) derived H₂S is a novel gasotransmitter and plays a critical role in the preservation of cardiac functions. Selenocysteine lyase (SCLY) has been identified to produce H₂Se, the selenium homologue of H₂S. Deficiency of selenium is often found in Keshan disease, a congestive cardiomyopathy. The interaction of H₂S and H₂Se in cardiac cell hypertrophy has not been explored. In this study, cell viability was evaluated with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Oxidative stress and cell size were observed through immunostaining. The expression of genes was determined by real-time PCR and western blot. Here, we demonstrated that incubation of rat cardiac cells (H9C2) with H₂O₂ lead to increased oxidative stress and cell surface area, which were significantly attenuated by pretreatment of either H₂S or H₂Se. H₂S incubation induced SCLY/H₂Se signaling, which next caused higher expressions and activities of selenoproteins, including glutathione peroxidase and thioredoxin reductase. Furthermore, deficiency of CSE inhibited the expressions of SCLY and selenoprotein P in mouse heart tissues. We also found that both H₂S and H₂Se stimulated Nrf2-targeted downstream genes. These data suggests that H₂S protects against cardiac hypertrophy through enhancement of a group of antioxidant proteins.