@article{3020940,
    title = "3-Mercaptopyruvate sulfurtransferase supports endothelial cell angiogenesis and bioenergetics",
    author = "Abdollahi Govar, A. and Törő, G. and Szaniszlo, P. and Pavlidou, A. and Bibli, S.-I. and Thanki, K. and Resto, V.A. and Chao, C. and Hellmich, M.R. and Szabo, C. and Papapetropoulos, A. and Módis, K.",
    journal = "British Journal of Pharmacology",
    year = "2020",
    volume = "177",
    number = "4",
    pages = "866-883",
    publisher = "John Wiley and Sons Inc",
    issn = "0007-1188, 1476-5381",
    doi = "10.1111/bph.14574",
    keywords = "3 mercaptopyruvate sulfurtransferase;  adenosine triphosphate;  glucose;  short hairpin RNA;  vasculotropin, angiogenesis;  Article;  cell energy;  cell metabolism;  cell migration;  cell proliferation;  cell respiration;  controlled study;  endothelium cell;  enzyme activity;  glucose transport;  glycolysis;  human;  human cell;  in vitro study;  metabolome;  metabolomics;  mitochondrion;  priority journal",
    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 (H2S), 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 H2S-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. © 2019 The British Pharmacological Society"
}