Τίτλος:
3-Mercaptopyruvate sulfurtransferase supports endothelial cell angiogenesis and bioenergetics
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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
Συγγραφείς:
Abdollahi Govar, A.
Törő, G.
Szaniszlo, P.
Pavlidou, A.
Bibli, S.-I.
Thanki, K.
Resto, V.A.
Chao, C.
Hellmich, M.R.
Szabo, C.
Papapetropoulos, A.
Módis, K.
Περιοδικό:
British Journal of Pharmacology
Εκδότης:
John Wiley and Sons Inc
Λέξεις-κλειδιά:
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
