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

J. Biol. Chem., Vol. 280, Issue 29, 26913-26921, July 22, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/29/26913    most recent M500068200v1 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 Hörnig, C. Articles by Werz, O. Search for Related Content PubMed PubMed Citation Articles by Hörnig, C. Articles by Werz, O. Social Bookmarking                      What's this?

1-Oleoyl-2-acetylglycerol Stimulates 5-Lipoxygenase Activity via a Putative (Phospho)lipid Binding Site within the N-terminal C2-like Domain^*

Christina Hörnig, Dana Albert, Lutz Fischer, Michael Hörnig, Olof Rådmark, Dieter Steinhilber, and Oliver Werz¶

From the Institute of Pharmaceutical Chemistry, ZAFES, University of Frankfurt, D-60439 Frankfurt, Germany and Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, S-171 77 Stockholm, Sweden

5-Lipoxygenase (5-LO) catalysis is positively regulated by Ca²⁺ ions and phospholipids that both act via the N-terminal C2-like domain of 5-LO. Previously, we have shown that 1-oleoyl-2-acetylglycerol (OAG) functions as an agonist for human polymorphonuclear leukocytes (PMNL) in stimulating 5-LO product formation. Here we have demonstrated that OAG directly stimulates 5-LO catalysis in vitro. In the absence of Ca²⁺ (chelated using EDTA), OAG strongly and concentration-dependently stimulated crude 5-LO in 100,000 x g supernatants as well as purified 5-LO enzyme from PMNL. Also, the monoglyceride 1-O-oleyl-rac-glycerol and 1,2-dioctanoyl-sn-glycerol were effective, whereas various phospholipids did not stimulate 5-LO. However, in the presence of Ca²⁺, OAG caused no stimulation of 5-LO. Also, phospholipids or cellular membranes abolished the effects of OAG. As found previously for Ca²⁺, OAG renders 5-LO activity resistant against inhibition by glutathione peroxidase activity, and this effect of OAG is reversed by phospholipids. Intriguingly, a 5-LO mutant lacking tryptophan residues (Trp-13, -75, and -102) important for the binding of the 5-LO C2-like domain to phospholipids was not stimulated by OAG. We conclude that OAG directly stimulates 5-LO by acting at a phospholipid binding site located within the C2-like domain.

Received for publication, January 4, 2005 , and in revised form, May 10, 2005.

^* This study was supported by grants from the European Union (QLG1-CT-2001-01521, LSHM-CT-2004-0050333). 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: Institute of Pharmaceutical Chemistry, University of Frankfurt, Marie-Curie-Str. 9, D-60439 Frankfurt, Germany. Tel.: 49-69-798 29337; Fax: 49-69-798 29323; E-mail: o.werz{at}pharmchem.uni-frankfurt.de.

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

This article has been cited by other articles:

				D. Albert, C. Pergola, A. Koeberle, G. Dodt, D. Steinhilber, and O. Werz The role of diacylglyceride generation by phospholipase D and phosphatidic acid phosphatase in the activation of 5-lipoxygenase in polymorphonuclear leukocytes J. Leukoc. Biol., April 1, 2008; 83(4): 1019 - 1027. [Abstract] [Full Text] [PDF]

				M. Rakonjac, L. Fischer, P. Provost, O. Werz, D. Steinhilber, B. Samuelsson, and O. Radmark Coactosin-like protein supports 5-lipoxygenase enzyme activity and up-regulates leukotriene A4 production PNAS, August 29, 2006; 103(35): 13150 - 13155. [Abstract] [Full Text] [PDF]