TY - JOUR
T1 - 3-Mercaptopyruvate sulfurtransferase supports endothelial cell angiogenesis and bioenergetics
AU - Abdollahi Govar, Armita
AU - Törő, Gábor
AU - Szaniszlo, Peter
AU - Pavlidou, Athanasia
AU - Bibli, Sofia Iris
AU - Thanki, Ketan
AU - Resto, Vicente A.
AU - Chao, Celia
AU - Hellmich, Mark R.
AU - Szabo, Csaba
AU - Papapetropoulos, Andreas
AU - Módis, Katalin
N1 - Funding Information:
Foundation for the National Institutes of Health, Grant/Award Numbers: R01CA175803 and T32 DK007639; Swiss National Foundation, Grant/Award Number: 31003A_179434; National Institutes of Health, Grant/Award Numbers: T32 DK007639 and R01CA175803; Bodossakis Foundation; American Heart Association, Grant/Award Number: 16SDG29860009
Funding Information:
K.M. would like to thank Dr Kasia Broniowska for the helpful discussions during the analysis of the metabolomic data and Dr Emily Mercadante for her assistance in the preparation of this manuscript. This work was supported by the American Heart Association, Scientist Development Grant (16SDG29860009) to K.M. The project was also benefited additional funding sources: Bodossakis Foundation to S‐I.B. and A. Papapetropoulos, National Institutes of Health (R01CA175803 to C.S. and M.R.H.; T32 DK007639 to M.R.H.), and the Swiss National Foundation (31003A_179434) to C.S.
Publisher Copyright:
© 2019 The British Pharmacological Society
PY - 2020/2/1
Y1 - 2020/2/1
N2 - 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.
AB - 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.
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U2 - 10.1111/bph.14574
DO - 10.1111/bph.14574
M3 - Article
C2 - 30644090
AN - SCOPUS:85062537290
SN - 0007-1188
VL - 177
SP - 866
EP - 883
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 4
ER -