Skip Navigation

Cardiovascular Research 2004 63(2):338-346; doi:10.1016/j.cardiores.2004.04.025
© 2004 by European Society of Cardiology
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Weis, M. T
Right arrow Articles by Stallone, J. N
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Weis, M. T
Right arrow Articles by Stallone, J. N
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2004, European Society of Cardiology

Inhibiting long chain fatty Acyl CoA synthetase increases basal and agonist-stimulated NO synthesis in endothelium

Margaret T Weis*,a, Jason L Crumleya, Lindon H Youngb and John N Stallonec

aDepartment of Pharmaceutical Sciences, Texas Tech University Health Science Center, 1300 Coulter, Amarillo, TX 79106, USA
bDepartment of Pathology, Philadelphia College of Osteopathic Medicine, Philadelphia, PA 19131, USA
cDepartment of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA

* Corresponding author. Tel.: +1-806-356-4015x281; fax: +1-806-356-4034. Email address: margaret.weis{at}tuuhsc.edu

Objectives: Endothelial nitric oxide synthase (eNOS) activation/deactivation is associated with cyclic depalmitoylation/repalmitoylation of specific Cys residues. The mechanism of depalmitoylation has been identified recently, but repalmitoylation remains undefined. We hypothesized that long chain fatty acyl CoA synthetase (LCFACoAS) modulates endothelial nitric oxide synthase repalmitoylation by limiting palmitoyl CoA availability. Methods: Human coronary endothelial cells were treated with triacsin-C, an inhibitor of long chain fatty acyl CoA synthetase, for 24 h. Media nitrite accumulation, eNOS activity, and eNOS palmitoylation were measured. Methacholine-induced NO synthesis or vascular relaxation were measured in endothelium-intact rat aortae in the presence and absence of triacsin-C. Results: Triacsin-C significantly reduced incorporation of [3H] palmitate into immunoreactive endothelial nitric oxide synthase and over a concentration range of 0.1 to 10 µM, increased media nitrite accumulations 2- to 2.5-fold over baseline. Total in vitro catalytic activity of nitric oxide synthase in triacsin-C treated cells did not differ significantly from control. Triacsin-C significantly increased methacholine-induced NO synthesis in the isolated rat aorta, and significantly enhanced methacholine-induced relaxation of rat aortic rings. Conclusions: These data are consistent with the interpretation that inhibition of palmitoylation increases endothelial nitric oxide synthase activity without changing endothelial nitric oxide synthase expression, suggesting that inhibiting palmitoylation increases the catalytically active fraction of endothelial nitric oxide synthase.

KEYWORDS Coronary circulation; Endothelial factors; Endothelial function; Hypertension; Nitric oxide

{star} Supported by NIH HL48204, NIH AG022614 [GenBank] , and Women's Health Research Institute of Amarillo.

Time for Primary Review 25 days


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Cardiovasc ResHome page
O. Feron and J.-L. Balligand
Caveolins and the regulation of endothelial nitric oxide synthase in the heart
Cardiovasc Res, March 1, 2006; 69(4): 788 - 797.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.