Advertisement
J. Lipid Res.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1194/jlr.M300463-JLR200 on May 16, 2004

Papers In Press, published online ahead of print August 1, 2004
J. Lipid Res., doi:10.1194/jlr.M300463-JLR200
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow All Versions of this Article:
M300463-JLR200v1
45/8/1446    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
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 Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Le Quéré, V.
Right arrow Articles by Salaün, J.-P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Le Quéré, V.
Right arrow Articles by Salaün, J.-P.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Journal of Lipid Research, Vol. 45, 1446-1458, August 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Human CYP4F3s are the main catalysts in the oxidation of fatty acid epoxides

Valérie Le Quéré*, Emmanuelle Plée-Gautier*, Philippe Potin{dagger}, Stéphanie Madec{dagger} and Jean-Pierre Salaün1,{dagger}

* Laboratoire de Biochimie-Equipe d'Accueil 948, Université de Bretagne Occidentale, Faculté de Médecine, CS 93837, 29238 Brest Cédex 3, France
{dagger} Unité Mixte de Recherche 7139 Centre National de la Recherche Scientifique/Goëmar/Université Pierre et Marie Curie, Station Biologique, 29682 Roscoff, France

1 To whom correspondence should be addressed. e-mail: jp.salaun{at}univ-brest.fr

CYP4F isoforms are involved in the oxidation of important cellular mediators such as leukotriene B4 (LTB4) and prostaglandins. The proinflammatory agent LTB4 and cytotoxic leukotoxins have been associated with several inflammatory diseases. We present evidence that the hydroxylation of Z 9(10)-epoxyoctadecanoic, Z 9(10)-epoxyoctadec-Z 12-enoic, and Z 12(13)-epoxyoctadec-Z 9-enoic acids and that of monoepoxides from arachidonic acid [epoxyeicosatrienoic acid (EET)] is important in the regulation of leukotoxin and EET activity. These three epoxidized derivatives from the C18 family (C18-epoxides) were converted to 18-hydroxy-C18-epoxides by human hepatic microsomes with apparent Km values of between 27.6 and 175 µM. Among recombinant P450 enzymes, CYP4F2 and CYP4F3B catalyzed mainly the {omega}-hydroxylation of C18-epoxides with an apparent Vmax of between 0.84 and 15.0 min–1, whereas the apparent Vmax displayed by CYP4F3A, the isoform found in leukocytes, ranged from 3.0 to 21.2 min–1. The rate of {omega}-hydroxylation by CYP4A11 was experimentally found to be between 0.3 and 2.7 min–1. CYP4F2 and CYP4F3 exhibited preferences for {omega}-hydroxylation of Z 8(9)-EET, whereas human liver microsomes preferred Z 11(12)-EET and, to a lesser extent, Z 8(9)-EET. Moreover, vicinal diol from both C18-epoxides and EETs were {omega}-hydroxylated by liver microsomes and by CYP4F2 and CYP4F3.

These data support the hypothesis that the human CYP4F subfamily is involved in the {omega}-hydroxylation of fatty acid epoxides. These findings demonstrate that another pathway besides conversion to vicinal diol or chain shortening by ß-oxidation exists for fatty acid epoxide inactivation.

Abbreviations: AA, arachidonic acid; BSTFA, N,O-bistrimethylsilyltrifluoroacetamide; C18-epoxides, epoxidized derivatives from the C18 family; DHET, dihydroxyeicosatrienoic acid; DiOME, dihydroxyC18:1 acid (vicinal diol); DiSTA, dihydroxystearic acid (vicinal diol); EET, epoxyeicosatrienoic acid; EH, epoxide hydrolase; HEET, hydroxyepoxyeicosatrienoic acid; HEpOME, hydroxyepoxyoctadecanoic acid; HEpSTA, hydroxy-9(10)-epoxyoctadecanoic acid; HETE, hydroxyeicosatetraenoic acid; LC-MS, liquid chromatography-mass spectrometry; LTB4, leukotriene B4; Me/TMS, methyl ester trimethylsilyl ether; PPAR{alpha}, peroxisome proliferator-activated receptor {alpha}; RP, reversed-phase; Rt, retention time; TMCS, trimethylchlorosilane; TriHET, trihydroxyeicosatrienoic acid; TriSTA, trihydroxystearic acid (triol); Z 9(10)-EpOME, Z 9(10)-epoxyoctadec-Z 12-enoic acid; Z 12(13)-EpOME, Z 12(13)-epoxyoctadec-Z 9-enoic acid; Z 9(10)-EpSTA, Z 9(10)-epoxyoctadecanoic acid (epoxystearic acid)

Supplementary key words leukotoxin • epoxyeicosatrienoic acid • cytochrome P450 • oxylipin • liver • microsomes • recombinant cytochrome P450 • hydroxylation


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


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
D. W. Nebert and C. L. Karp
Endogenous Functions of the Aryl Hydrocarbon Receptor (AHR): Intersection of Cytochrome P450 1 (CYP1)-metabolized Eicosanoids and AHR Biology
J. Biol. Chem., December 26, 2008; 283(52): 36061 - 36065.
[Full Text] [PDF]

Home page
 J. Lipid Res.Home page
M. Fer, L. Corcos, Y. Dreano, E. Plee-Gautier, J.-P. Salaun, F. Berthou, and Y. Amet
Cytochromes P450 from family 4 are the main omega hydroxylating enzymes in humans: CYP4F3B is the prominent player in PUFA metabolism
J. Lipid Res., November 1, 2008; 49(11): 2379 - 2389.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
J. Antoun, S. Goulitquer, Y. Amet, Y. Dreano, J.-P. Salaun, L. Corcos, and E. Plee-Gautier
CYP4F3B is induced by PGA1 in human liver cells: a regulation of the 20-HETE synthesis
J. Lipid Res., October 1, 2008; 49(10): 2135 - 2141.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
A. Kalsotra, L. Du, Y. Wang, P. A. Ladd, Y. Kikuta, M. Duvic, A. S. Boyd, D. S. Keeney, and H. W. Strobel
Inflammation resolved by retinoid X receptor-mediated inactivation of leukotriene signaling pathways
FASEB J, February 1, 2008; 22(2): 538 - 547.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
A. Gatica, M. C. Aguilera, D. Contador, G. Loyola, C. O. Pinto, L. Amigo, J. E. Tichauer, S. Zanlungo, and M. Bronfman
P450 CYP2C epoxygenase and CYP4A {omega}-hydroxylase mediate ciprofibrate-induced PPAR{alpha}-dependent peroxisomal proliferation
J. Lipid Res., April 1, 2007; 48(4): 924 - 934.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
A. Gaedigk, D. W. Baker, R. A. Totah, R. Gaedigk, R. E. Pearce, C. A. Vyhlidal, D. C. Zeldin, and J. S. Leeder
Variability of CYP2J2 Expression in Human Fetal Tissues
J. Pharmacol. Exp. Ther., November 1, 2006; 319(2): 523 - 532.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
H.-Q. Yin, M. Kim, J.-H. Kim, G. Kong, M.-O. Lee, K.-S. Kang, B.-I. Yoon, H.-L. Kim, and B.-H. Lee
Hepatic Gene Expression Profiling and Lipid Homeostasis in Mice Exposed to Steatogenic Drug, Tetracycline
Toxicol. Sci., November 1, 2006; 94(1): 206 - 216.
[Abstract] [Full Text] [PDF]

Home page
 J Exp BotHome page
F. C. Kupper, E. Gaquerel, E.-M. Boneberg, S. Morath, J.-P. Salaun, and P. Potin
Early events in the perception of lipopolysaccharides in the brown alga Laminaria digitata include an oxidative burst and activation of fatty acid oxidation cascades
J. Exp. Bot., June 1, 2006; 57(9): 1991 - 1999.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Journal of Biological Chemistry 
 Molecular and Cellular Proteomics   ASBMB Today 
Copyright © 2004 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement