Crosstalk between hydrogen sulfide and nitric oxide in endothelial cells

Journal of Cellular and Molecular Medicine

Zaid Altaany¹  Guangdong Yang² 

[1] Department of Biology, Lakehead University, Thunder Bay, Ontario, Canada;The School of Kinesiology, Lakehead University, Thunder Bay, Ontario, Canada

关键词: Hydrogen sulfide;    Nitric oxide;    Endothelial cells;    eNOS;    CSE;    Cystathionine gamma‐lyase;   

DOI  :  10.1111/jcmm.12077

来源: Wiley

【 摘 要 】

Abstract

Hydrogen sulfide (H₂S) and nitric oxide (NO) are major gasotransmitters produced in endothelial cells (ECs), contributing to the regulation of vascular contractility and structural integrity. Their interaction at different levels would have a profound impact on angiogenesis. Here, we showed that H₂S and NO stimulated the formation of new microvessels. Incubation of human umbilical vein endothelial cells (HUVECs-926) with NaHS (a H₂S donor) stimulated the phosphorylation of endothelial NO synthase (eNOS) and enhanced NO production. H₂S had little effect on eNOS protein expression in ECs. L-cysteine, a precursor of H₂S, stimulated NO production whereas blockage of the activity of H₂S-generating enzyme, cystathionine gamma-lyase (CSE), inhibited this action. CSE knockdown inhibited, but CSE overexpression increased, NO production as well as EC proliferation. LY294002 (Akt/PI3-K inhibitor) or SB203580 (p38 MAPK inhibitor) abolished the effects of H₂S on eNOS phosphorylation, NO production, cell proliferation and tube formation. Blockade of NO production by eNOS-specific siRNA or nitro-L-arginine methyl ester (L-NAME) reversed, but eNOS overexpression potentiated, the proliferative effect of H₂S on ECs. Our results suggest that H₂S stimulates the phosphorylation of eNOS through a p38 MAPK and Akt-dependent pathway, thus increasing NO production in ECs and vascular tissues and contributing to H₂S-induced angiogenesis.

【 授权许可】

CC BY   
© 2013 The Authors. Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.