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SIRT3 Mediates the Antioxidant Effect of Hydrogen Sulfide in Endothelial Cells.
Antioxid Redox Signal 2016; 24(6):329-43AR

Abstract

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.

Authors+Show Affiliations

1 Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University , Nanjing, China .1 Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University , Nanjing, China .1 Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University , Nanjing, China .1 Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University , Nanjing, China . 2 Department of Pharmacology, School of Pharmacy, Nantong University , Nantong, China .1 Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University , Nanjing, China .1 Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University , Nanjing, China .1 Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University , Nanjing, China .3 Department of Geriatrics, the First Affiliated Hospital of Nanjing Medical University , Nanjing, China .1 Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University , Nanjing, China .1 Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University , Nanjing, China .4 Department of Cardiothoracic Surgery, the First Affiliated Hospital of Nanjing Medical University , Nanjing, China .5 Department of Chemistry, Washington State University , Pullman, Washington.5 Department of Chemistry, Washington State University , Pullman, Washington.6 Institute of Vascular Biology, Chinese University of Hong Kong , Hong Kong, China .7 Cardiovascular Division, Department of Clinical Pharmacology, School of Medicine, King's College London , London, United Kingdom .8 Department of Biology, Cardivascular and Molecular Research Unit, Lakehead University , Thunder Bay, Ontario, Canada .9 Department of Pharmacology, National University of Singapore , Singapore .10 Department of Pharmacology, Center for Metabolic Disease Research, Temple University School of Medicine , Philadelphia, Pennsylvania.1 Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University , Nanjing, China .

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26422756

Citation

Xie, Liping, et al. "SIRT3 Mediates the Antioxidant Effect of Hydrogen Sulfide in Endothelial Cells." Antioxidants & Redox Signaling, vol. 24, no. 6, 2016, pp. 329-43.
Xie L, Feng H, Li S, et al. SIRT3 Mediates the Antioxidant Effect of Hydrogen Sulfide in Endothelial Cells. Antioxid Redox Signal. 2016;24(6):329-43.
Xie, L., Feng, H., Li, S., Meng, G., Liu, S., Tang, X., ... Ji, Y. (2016). SIRT3 Mediates the Antioxidant Effect of Hydrogen Sulfide in Endothelial Cells. Antioxidants & Redox Signaling, 24(6), pp. 329-43. doi:10.1089/ars.2015.6331.
Xie L, et al. SIRT3 Mediates the Antioxidant Effect of Hydrogen Sulfide in Endothelial Cells. Antioxid Redox Signal. 2016 Feb 20;24(6):329-43. PubMed PMID: 26422756.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SIRT3 Mediates the Antioxidant Effect of Hydrogen Sulfide in Endothelial Cells. AU - Xie,Liping, AU - Feng,Haihua, AU - Li,Sha, AU - Meng,Guoliang, AU - Liu,Shangmin, AU - Tang,Xin, AU - Ma,Yan, AU - Han,Yi, AU - Xiao,Yujiao, AU - Gu,Yue, AU - Shao,Yongfeng, AU - Park,Chung-Min, AU - Xian,Ming, AU - Huang,Yu, AU - Ferro,Albert, AU - Wang,Rui, AU - Moore,Philip K, AU - Wang,Hong, AU - Ji,Yong, Y1 - 2015/11/10/ PY - 2017/02/20/pmc-release PY - 2015/10/1/entrez PY - 2015/10/1/pubmed PY - 2016/12/20/medline SP - 329 EP - 43 JF - Antioxidants & redox signaling JO - Antioxid. Redox Signal. VL - 24 IS - 6 N2 - 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. SN - 1557-7716 UR - https://www.unboundmedicine.com/medline/citation/26422756/SIRT3_Mediates_the_Antioxidant_Effect_of_Hydrogen_Sulfide_in_Endothelial_Cells_ L2 - https://www.liebertpub.com/doi/full/10.1089/ars.2015.6331?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -