Regulation of vascular guanylyl cyclase by endothelial nitric oxide-dependent posttranslational modification
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Marc Oppermann Tatsiana Suvorava Till Freudenberger Vu Thao-Vi Dao Jens W. Fischer Martina Weber Georg Kojda
- چاپ و سال / کشور: 2011
Description
In isolated cells, soluble guanylyl cyclase (sGC) activity is regulated by exogenous nitric oxide (NO) via downregulation of expression and posttranslational S-nitrosylation. The aim of this study was to investigate whether such regulatory mechanism impact on endothelium- dependent vasodilation in a newly developed mouse strain carrying an endothelial-specific overexpression of eNOS (eNOS??). When compared with transgene negative controls (eNOSn), eNOS??-mice showed a 3.3-fold higher endothelial-specific aortic eNOS expression, increased vascular cGMP and VASP phosphorylation, a L-nitroarginine (L-NA)-inhibitable decrease in systolic blood pressure, but normal levels of peroxynitrite and nitrotyrosine formation, endothelium-dependent aortic vasodilation and vasodilation to NO donors. Western blot analysis for sGC showed similar protein levels of sGC-a1 and sGC-b1 subunits in eNOSn and eNOS??. In striking contrast, the activity of isolated sGC was strongly decreased in lungs of eNOS??. Semiquantitative evaluation of sGC-b1-S-nitrosylation demonstrated that this loss of sGC activity is associated with increased nitrosylation of the enzyme in eNOS??, a difference that disappeared after L-NA-treatment. Our data suggest the existence of a physiologic NOdependent posttranslational regulation of vascular sGC in mammals involving S-nitrosylation as a key mechanism. Because this mechanism can compensate for reduction in vascular NO bioavailability, it may mask the development of endothelial dysfunction
Basic Res Cardiol (2011) 106:539–549 Received: 3 September 2010 / Revised: 14 January 2011 / Accepted: 27 January 2011 / Published online: 6 February 2011
