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Xie L , Feng H , Li S , Meng G , Liu S , Tang X , Ma Y , Han Y , Xiao Y , Gu Y , Shao Y , Park CM , Xian M , Huang Y , Ferro A , Wang R , Moore PK , Wang H , Ji Y
SIRT3 Mediates the Antioxidant Effect of Hydrogen Sulfide in Endothelial Cells
Antioxid Redox Signal. 2016 Feb 20;24(6) :329-43
PMID: 26422756    PMCID: PMC4761821    URL: http://www.ncbi.nlm.nih.gov/pubmed/26422756
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AIM: Oxidative stress is a key contributor to endothelial dysfunction and associated cardiovascular pathogenesis. Hydrogen sulfide (H2S) is an antioxidant gasotransmitter that protects endothelial cells against oxidative stress. Sirtuin3 (SIRT3), which belongs to the silent information regulator 2 (SIR2) family, is an important deacetylase under oxidative stress. H2S is able to regulate the activity of several sirtuins. The present study aims to investigate the role of SIRT3 in the antioxidant effect of H2S in endothelial cells. RESULTS: Cultured EA.hy926 endothelial cells were exposed to hydrogen peroxide (H2O2) as a model of oxidative stress-induced cell injury. GYY4137, a slow-releasing H2S donor, improved cell viability, reduced oxidative stress and apoptosis, and improved mitochondrial function following H2O2 treatment. H2S reversed the stimulation of MAPK phosphorylation, downregulation of SIRT3 mRNA and reduction of the superoxide dismutase 2 and isocitrate dehydrogenase 2 expression which were induced by H2O2. H2S also increased activator protein 1 (AP-1) binding activity with SIRT3 promoter and this effect was absent in the presence of the specific AP-1 inhibitor, SR11302 or curcumin. Paraquat administration to mice induced a defected endothelium-dependent aortic vasodilatation and increased oxidative stress in both mouse aorta and small mesenteric artery, which were alleviated by GYY4137 treatment. This vasoprotective effect of H2S was absent in SIRT3 knockout mice. INNOVATION: The present results highlight a novel role for SIRT3 in the protective effect of H2S against oxidant damage in the endothelium both in vitro and in vivo. CONCLUSION: H2S enhances AP-1 binding activity with the SIRT3 promoter, thereby upregulating SIRT3 expression and ultimately reducing oxidant-provoked vascular endothelial dysfunction. Antioxid. Redox Signal. 24, 329-343.
Xie, Liping Feng, Haihua Li, Sha Meng, Guoliang Liu, Shangmin Tang, Xin Ma, Yan Han, Yi Xiao, Yujiao Gu, Yue Shao, Yongfeng Park, Chung-Min Xian, Ming Huang, Yu Ferro, Albert Wang, Rui Moore, Philip K Wang, Hong Ji, Yong ENG R01 HL077288/HL/NHLBI NIH HHS/ R01 HL110764/HL/NHLBI NIH HHS/ R01HL116571/HL/NHLBI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2015/10/01 06:00 Antioxid Redox Signal. 2016 Feb 20;24(6):329-43. doi: 10.1089/ars.2015.6331. Epub 2015 Nov 10.