Search

Oxidative stress plays a great role in the pathogenesis of heart failure (HF). Oxidative stress results in apoptosis, which can cause the damage of cardiomyocytes. Hydrogen sulfide (H2S), the third gasotransmitter, is a good reactive oxygen species (ROS) scavenger, which has protective effect against HF. Sirtuin-1 (SIRT1) is a highly conserved nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase that plays a critical role in promoting cell survival under oxidative stress. The purpose of this article is to investigate the interaction between H2S and SIRT1 under oxidative stress in H9c2 cardiomyocytes. Oxidative stress was induced by hydrogen peroxide (H2O2). Treatment with NaSH (25-100 µmol/L) dose-dependently increased the cell viability and improved the cell apoptosis induced by H2O2 in H9c2 cardiomyocytes. The protective effect of NaSH against the apoptosis could be attenuated by SIRT1 inhibitor Ex 527 (10 µmol/L). Treatment with NaSH (100 µmol/L) could increase the expression of SIRT1 in time dependent manner, which decreased by different concentration of H2O2. NaSH (100 µmol/L) increased the cellular ATP level and the expression of ATPase. These effects were attenuated by Ex 527 (10 µmol/L). After NaSH (100 µmol/L) treatment, the decrease in ROS production and the enhancement in SOD, GPx and GST expression were observed. Ex 527 (10 µmol/L) reversed these effects. In conclusion, for the first time, this article can identify antioxidative effects of H2S under oxidative stress through SIRT1 pathway in H9c2 cardiomyocytes., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Hydrogen sulfide (H2S) is known to have pro-angiogenic properties in mammals. In this study, we examined H2S played the role in pro-angiogenesis mediated by hypoxia-inducible factor (HIF)-1alpha under hypoxic conditions. Rat brain capillary endothelial cells (ECs) were treated with NaHS (a H2S donor) pretreated vascular smooth muscle cells (VSMCs) conditioned media. ECs proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. ECs migration was assessed by chemotaxis chamber assay. Angiogenesis-associated gene expression levels were determined by reverse transcription-polymerase chain reaction (RT-PCR). HIF-1alpha and vascular endothelial growth factor (VEGF) accumulation was analyzed by Western blotting. HIF-1 binding activity was measured by electrophoretic mobility shift assay (EMSA). We found H2S induced both endothelial proliferation and migration in mimic hypoxic condition. In addition, H2S promoted VEGF and HIF-1alpha mRNA levels. H2S also significantly upregulated HIF-1alpha and VEGF protein levels and increased HIF-1alpha binding activity under hypoxic condition. Our findings suggest that HIF-1/VEGF is involved in H2S promotes proliferation and migration of ECs.

Abstract: Leonurine, an alkaloid typically found in Herba leonuri, is known to have both antioxidant and cardioprotective properties. In the present study, we investigated the cardioprotective mechanism of leonurine the in vivo rat model of chronic myocardial ischemia and in vitro H9c2 cardiac myocyte model of oxidative stress. Myocardial ischemia was induced by ligating the left anterior descending coronary artery. Rats were divided into sham, myocardial ischemia+saline, and myocardial ischemia+leonurine (15mg/kg/day). Cardiac function was recorded by catheterization. Apoptosis-related factor vascular endothelial growth factor (VEGF), survivin, Bcl-2 and Bax and pro-survival signaling pathways Akt, hypoxia inducible factor (HIF)-1α were measured by Western blotting or RT-PCR. Our results showed leonurine significantly improved myocardial function as evidenced by the decreased left ventricle end-diastolic pressure and the increased +dP/dt. Interestingly, leonurine increased the phosphorylation of Akt, the protein and gene expression of Bcl-2, but it reduced the protein and gene expression of Bax in vivo. Meanwhile leonurine significantly increased Akt phosphorylation in a concentration-dependent manner in H9c2 cardiac myocyte induced by oxidative stress in vitro, which was abolished by a phosphoinositide 3-kinase (PI3K) inhibitor, LY294002. Furthermore, leonurine not only increased the expression of HIF-1α but also the expression of survivin and VEGF. The results of present study demonstrated, for the first time that leonurine has potent anti-apoptotic effects after chronic myocardial ischemia mediated by activating the PI3K/Akt signaling pathway. Angiogenic mechanisms may be partially responsible for such an effect, which needs to be studied further. [ABSTRACT FROM AUTHOR]