Journal article
SIRT3 Mediates the Antioxidant Effect of Hydrogen Sulfide in Endothelial Cells
Antioxidants & redox signaling, Vol.24(6), pp.329-343
02/20/2016
Handle:
https://hdl.handle.net/2376/110064
PMCID: PMC4761821
PMID: 26422756
Abstract
Aim:
Oxidative stress is a key contributor to endothelial dysfunction and associated cardiovascular pathogenesis. Hydrogen sulfide (H
2
S) 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. H
2
S is able to regulate the activity of several sirtuins. The present study aims to investigate the role of SIRT3 in the antioxidant effect of H
2
S in endothelial cells.
Results:
Cultured EA.hy926 endothelial cells were exposed to hydrogen peroxide (H
2
O
2
) as a model of oxidative stress-induced cell injury. GYY4137, a slow-releasing H
2
S donor, improved cell viability, reduced oxidative stress and apoptosis, and improved mitochondrial function following H
2
O
2
treatment. H
2
S 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 H
2
O
2
. H
2
S 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 H
2
S was absent in
SIRT3
knockout mice.
Innovation:
The present results highlight a novel role for SIRT3 in the protective effect of H
2
S against oxidant damage in the endothelium both
in vitro
and
in vivo.
Conclusion:
H
2
S 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.
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Details
- Title
- SIRT3 Mediates the Antioxidant Effect of Hydrogen Sulfide in Endothelial Cells
- Creators
- Liping Xie - 1Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, ChinaHaihua Feng - 1Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, ChinaSha Li - 1Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, ChinaGuoliang Meng - 2Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, ChinaShangmin Liu - 1Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, ChinaXin Tang - 1Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, ChinaYan Ma - 1Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, ChinaYi Han - 3Department of Geriatrics, the First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaYujiao Xiao - 1Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, ChinaYue Gu - 1Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, ChinaYongfeng Shao - 4Department of Cardiothoracic Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaChung-Min Park - 5Department of Chemistry, Washington State University, Pullman, WashingtonMing Xian - 5Department of Chemistry, Washington State University, Pullman, WashingtonYu Huang - 6Institute of Vascular Biology, Chinese University of Hong Kong, Hong Kong, ChinaAlbert Ferro - 7Cardiovascular Division, Department of Clinical Pharmacology, School of Medicine, King's College London, London, United KingdomRui Wang - 8Department of Biology, Cardivascular and Molecular Research Unit, Lakehead University, Thunder Bay, Ontario, CanadaPhilip K Moore - 9Department of Pharmacology, National University of Singapore, SingaporeHong Wang - 10Department of Pharmacology, Center for Metabolic Disease Research, Temple University School of Medicine, Philadelphia, PennsylvaniaYong Ji - 1Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China
- Publication Details
- Antioxidants & redox signaling, Vol.24(6), pp.329-343
- Academic Unit
- Chemistry, Department of
- Publisher
- Mary Ann Liebert, Inc
- Identifiers
- 99900546914701842
- Language
- English
- Resource Type
- Journal article