Abstract
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.
Highlights
Cardiovascular disease (CVD) is a leading cause of death world-wide contributing to approximately 31% of all deaths annually
Lower doses of reactive oxygen species (ROS) usually contribute to chronic stress eventually leading to cellular apoptosis through metabolic starvation, while higher doses of ROS can lead to significant cell death within a short period of time [1]
A major finding of this study is that pretreatment with 30 μM H2S or 0.3 μM H2Se protects H9C2 cardiac cells from higher doses of H2O2 (800 μM)-induced cellular death
Summary
Cardiovascular disease (CVD) is a leading cause of death world-wide contributing to approximately 31% of all deaths annually. More than 85% of all CVD-related deaths are contributed to or caused by heart attacks and strokes, both of which are typical end results of chronic pathologies, such as cardiac hypertrophy [1]. Cardiac hypertrophy is both a natural and responsive change where the myocardium undergoes overgrowth in response to external and internal stimuli, such as reactive oxygen species (ROS) or pressure overload [1, 2]. In cases where the oxygen and nutrient demand is not met, myocardial ischemic conditions persist, which will result in cardiac cell death, tissue fibrosis, and subsequent cardiac infarcture [3]. Two fetal genes atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) have long been used as molecular markers for the diagnosis of pathological hypertrophy [3,4,5]
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