Aim Oxidative stress is a key contributor to endothelial dysfunction and associated cardiovascular pathogenesis. Hydrogen sulfide (H2S) is an anti-oxidant gasotransmiter that protects endothelial cells against oxidative stress. Sirtuin3 (SIRT3), which belongs to silent information regulator 2 (SIR2) family, is an important deacetylase under oxidative stress. H2S was 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 H2O2-mediated inhibition of MAPKs phosphorylation, down-regulated SIRT3 mRNA and enhanced expression of superoxide dismutase 2 and isocitrate dehydrogenase 2. 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 vaso-protective 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 endothelium both in vitro and in vivo. Conclusion H2S enhances AP-1 binding activity with the SIRT3 promoter, thereby up-regulating SIRT3 expression and ultimately reducing oxidant-provoked vascular endothelial dysfunction.
Pharmacology, Toxicology and Pharmaceutical Science
4
7%
Other
10
17%
Unknown
12
20%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 February 2016.
All research outputs
#26,248,041
of 32,787,243 outputs
Outputs from Antioxidants & Redox Signaling
#1,802
of 2,284 outputs
Outputs of similar age
#236,239
of 328,198 outputs
Outputs of similar age from Antioxidants & Redox Signaling
#13
of 21 outputs
Altmetric has tracked 32,787,243 research outputs across all sources so far. This one is in the 17th percentile – i.e., 17% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,284 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.7. This one is in the 18th percentile – i.e., 18% of its peers scored the same or lower than it.
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We're also able to compare this research output to 21 others from the same source and published within six weeks on either side of this one. This one is in the 28th percentile – i.e., 28% of its contemporaries scored the same or lower than it.
