HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 33, 29543-29550, August 19, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/33/29543    most recent M501238200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhu, W. Articles by Smart, E. J. Search for Related Content PubMed PubMed Citation Articles by Zhu, W. Articles by Smart, E. J. Social Bookmarking                      What's this?

Myristic Acid Stimulates Endothelial Nitric-oxide Synthase in a CD36- and an AMP Kinase-dependent Manner^*

Weifei Zhu and Eric J. Smart

From the Department of Pediatrics, University of Kentucky, Lexington, Kentucky 40536

Dietary free fatty acids have been reported to have various effects on the endothelium including the generation of nitric oxide. The goal of the current study was to determine the mechanism whereby free fatty acid causes an increase in nitric oxide synthesis. The specific hypothesis tested was that free fatty acid association with CD36, a class B scavenger receptor, induces the activation of endothelial nitric-oxide synthase (eNOS). A human microvascular endothelial cell line and a transfected Chinese hamster ovary cell system were used to determine which free fatty acids stimulate eNOS. Surprisingly, only myristic acid, and to a lesser extent palmitic acid, stimulated eNOS. The stimulation of eNOS was dose- and time-dependent. Competition experiments with other free fatty acids and with a CD36-blocking antibody demonstrated that the effects of myristic acid on eNOS required association with CD36. Further mechanistic studies demonstrated that the effects of myristic acid on eNOS function were not dependent on PI 3-kinase, Akt kinase, or calcium. Pharmacological studies and dominant negative constructs were used to demonstrate that myristic acid/CD36 stimulation of eNOS activity was dependent on the activation of AMP kinase. These data demonstrate an unexpected link among myristic acid, CD36, AMP kinase, and eNOS activity.

Received for publication, February 2, 2005 , and in revised form, May 27, 2005.

^* This work was supported in part by COBRE Grant P20 RR15592 from the National Center for Research Resources, National Institutes of Health, and by Grants HL62844 and HL64056 from the NHLBI, National Institutes of Health (to E. J. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Pediatrics, University of Kentucky, 423 Sanders-Brown, 800 Limestone St., Lexington, KY 40536-0230. Tel.: 859-323-6412; Fax: 859-257-2120; E-mail: ejsmart{at}uky.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. White, T. Guerin, H. Swanson, S. Post, H. Zhu, M. Gong, J. Liu, W. V. Everson, X.-A. Li, G. A. Graf, et al. Diabetic HDL-associated myristic acid inhibits acetylcholine-induced nitric oxide generation by preventing the association of endothelial nitric oxide synthase with calmodulin Am J Physiol Cell Physiol, January 1, 2008; 294(1): C295 - C305. [Abstract] [Full Text] [PDF]

				J. S. Isenberg, Y. Jia, J. Fukuyama, C. H. Switzer, D. A. Wink, and D. D. Roberts Thrombospondin-1 Inhibits Nitric Oxide Signaling via CD36 by Inhibiting Myristic Acid Uptake J. Biol. Chem., May 25, 2007; 282(21): 15404 - 15415. [Abstract] [Full Text] [PDF]

				M. Pravenec and T. W. Kurtz Molecular Genetics of Experimental Hypertension and the Metabolic Syndrome: From Gene Pathways to New Therapies Hypertension, May 1, 2007; 49(5): 941 - 952. [Abstract] [Full Text] [PDF]