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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Endothelial nitric oxide synthase activity is inhibited by the plasma membrane calcium ATPase in human endothelial cells
Cardiovascular Research, Volume 87, No. 3, Year 2010
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Description
AimsNitric oxide (NO) plays a pivotal role in the regulation of cardiovascular physiology. Endothelial NO is mainly produced by the endothelial nitric oxide synthase (eNOS) enzyme. eNOS enzymatic activity is regulated at several levels, including Ca2+/calmodulin binding and the interaction of eNOS with associated proteins. There is emerging evidence indicating a role for the plasma membrane calcium ATPase (PMCA) as a negative regulator of Ca 2+/calmodulin-dependent signal transduction pathways via its interaction with partner proteins. The aim of our study was to investigate the possibility that the activity of eNOS is regulated through its association with endothelial PMCA.Methods and resultsWe show here a novel interaction between endogenous eNOS and PMCA in human primary endothelial cells. The interaction domains were located to the region 735-934 of eNOS and the catalytic domain of PMCA. Ectopic expression of PMCA in endothelial cells resulted in an increase in phosphorylation of the residue Thr-495 of endogenous eNOS. However, disruption of the PMCA-eNOS interaction by expression of the PMCA interaction domain significantly reversed the PMCA-mediated effect on eNOS phosphorylation. These results suggest that eNOS activity is negatively regulated via interaction with PMCA. Moreover, NO production by endothelial cells was significantly reduced by ectopic expression of PMCA.ConclusionOur results show strong evidence for a novel functional interaction between endogenous PMCA and eNOS in endothelial cells, suggesting a role for endothelial PMCA as a negative modulator of eNOS activity, and, therefore, NO-dependent signal transduction pathways. © 2010 The Author.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC2904661/bin/supp_87_3_440__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC2904661/bin/supp_cvq077_cvq077supp.pdf
Authors & Co-Authors
Holton, Marylouisa
United Kingdom, Wolverhampton
University of Wolverhampton
Mohamed, Tamer M.A.
United Kingdom, Manchester
The University of Manchester
Egypt, Zagazig
Faculty of Pharmacy
Oceandy, Delvac
United Kingdom, Manchester
The University of Manchester
Wang, Weiguang
United Kingdom, Wolverhampton
University of Wolverhampton
Lamas, Santiago
Spain, Madrid
Fundación Renal Íñigo Álvarez de Toledo Friat
Emerson, Michael
United Kingdom, London
National Heart and Lung Institute
Neyses, Ludwig
United Kingdom, Manchester
The University of Manchester
Armesilla, Angel L.
United Kingdom, Wolverhampton
University of Wolverhampton
Statistics
Citations: 57
Authors: 8
Affiliations: 5
Identifiers
Doi:
10.1093/cvr/cvq077
ISSN:
00086363
e-ISSN:
17553245
Research Areas
Noncommunicable Diseases