当前位置： SCI文献检索 > BRITISH JOURNAL OF PHARMACOLOGY期刊下所有文献 > 3-Mercaptopyruvate sulfurtransferase supports endothelial cell angiogenesis and bioenergetics.

3-Mercaptopyruvate sulfurtransferase supports endothelial cell angiogenesis and bioenergetics.

Abstract：

BACKGROUND AND PURPOSE:During angiogenesis, quiescent endothelial cells (ECs) are activated by various stimuli to form new blood vessels from pre-existing ones in physiological and pathological conditions. Many research groups have shown that hydrogen sulfide (H2 S), the newest member of the gasotransmitter family, acts as a proangiogenic factor. To date, very little is known about the regulatory role of 3-mercaptopyruvate sulfurtransferase (3-MST), an important H2 S-producing enzyme in ECs. The aim of our study was to explore the potential role of 3-MST in human EC bioenergetics, metabolism, and angiogenesis. EXPERIMENTAL APPROACH:To assess in vitro angiogenic responses, we used EA.hy926 human vascular ECs subjected to shRNA-mediated 3-MST attenuation and pharmacological inhibition of proliferation, migration, and tube-like network formation. To evaluate bioenergetic parameters, cell respiration, glycolysis, glucose uptake, and mitochondrial/glycolytic ATP production were measured. Finally, global metabolomic profiling was performed to determine the level of 669 metabolic compounds. KEY RESULTS:3-MST-attenuated ECs subjected to shRNA or pharmacological inhibition of 3-MST significantly reduced EC proliferation, migration, and tube-like network formation. 3-MST silencing also suppressed VEGF-induced EC migration. From bioenergetic and metabolic standpoints, 3-MST attenuation decreased mitochondrial respiration and mitochondrial ATP production, increased glucose uptake, and perturbed the entire EC metabolome. CONCLUSION AND IMPLICATIONS:3-MST regulates bioenergetics and morphological angiogenic functions in human ECs. The data presented in the current report support the view that 3-MST pathway may be a potential candidate for therapeutic modulation of angiogenesis. LINKED ARTICLES:This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Abdollahi Govar A,Törő G,Szaniszlo P,Pavlidou A,Bibli SI,Thanki K,Resto VA,Chao C,Hellmich MR,Szabo C,Papapetropoulos A,Módis K

doi

10.1111/bph.14574

subject

Has Abstract

pub_date

2020-02-01 00:00:00

pages

866-883

issue

eissn

0007-1188

issn

1476-5381

journal_volume

177

pub_type

杂志文章

在线工具

3-Mercaptopyruvate sulfurtransferase supports endothelial cell angiogenesis and bioenergetics.