H(2)S 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 H(2)S is a novel gasotransmitter and plays a critical role in the preservation of cardiac functions. Selenocysteine lyase (SCLY) has been identified to produce H(2)Se, the selenium homologue of H(2)S. Deficiency of selenium is often found in Keshan disease, a congestive cardiomyopathy. The interaction of H(2)S and H(2)Se 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 H(2)O(2) lead to increased oxidative stress and cell surface area, which were significantly attenuated by pretreatment of either H(2)S or H(2)Se. H(2)S incubation induced SCLY/H(2)Se 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 H(2)S and H(2)Se stimulated Nrf2-targeted downstream genes. These data suggests that H(2)S protects against cardiac hypertrophy through enhancement of a group of antioxidant proteins.