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

This Article Full Text Full Text (PDF) 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fang, X. Articles by Spector, A. A. Search for Related Content PubMed PubMed Citation Articles by Fang, X. Articles by Spector, A. A. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 41, 66-74, January 2000
Copyright © 2000 by Lipid Research, Inc.

Original Article

Conversion of epoxyeicosatrienoic acids (EETs) to chain-shortened epoxy fatty acids by human skin fibroblasts

Correspondence to: Arthur A. Spector

Epoxyeicosatrienoic acids (EETs), the eicosanoid biomediators synthesized from arachidonic acid by cytochrome P450 epoxygenases, are inactivated in many tissues by conversion to dihydroxyeicosatrienoic acids (DHETs). However, we find that human skin fibroblasts convert EETs mostly to chain-shortened epoxy-fatty acids and produce only small amounts of DHETs. Comparative studies with [5,6,8,9,11,12,14,15-³H]11,12-EET ([³H]11,12-EET) and [1-¹⁴C]11,12-EET demonstrated that chain-shortened metabolites are formed by removal of carbons from the carboxyl end of the EET. These metabolites accumulated primarily in the medium, but small amounts also were incorporated into the cell lipids. The most abundant 11,12-EET product was 7,8-epoxyhexadecadienoic acid (7,8-epoxy-16:2), and two of the others that were identified are 9,10-epoxyoctadecadienoic acid (9,10-epoxy-18:2) and 5,6-epoxytetradecaenoic acid (5,6-epoxy-14:1). The main epoxy-fatty acid produced from 14,15-EET was 10,11-epoxyhexadecadienoic acid (10,11-epoxy-16:2). [³H]8,9-EET was converted to a single metabolite with the chromatographic properties of a 16-carbon epoxy-fatty acid, but we were not able to identify this compound. Large amounts of the chain-shortened 11,12-EET metabolites were produced by long-chain acyl CoA dehydrogenase-deficient fibroblasts but not by Zellweger syndrome and acyl CoA oxidase-deficient fibroblasts.

We conclude that the chain-shortened epoxy-fatty acids are produced primarily by peroxisomal ß-oxidation. This may serve as an alternate mechanism for EET inactivation and removal from the tissues. However, it is possible that the epoxy-fatty acid products may have metabolic or functional effects and that the purpose of the ß-oxidation pathway is to generate these products.—Fang, X., T. L. Kaduce, M. VanRollins, N. L. Weintraub, and A. A. Spector. Conversion of epoxyeicosatrienoic acids (EETS) to chain-shorted epoxy fatty acids by human skin fibroblasts. J. Lipid Res. 2000. 41: 66;–74.

Supplementary key words: arachidonic acid, eicosanoids, cytochrome P450 epoxygenase, peroxisomes, ß-oxidation

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

This article has been cited by other articles:

				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]

				A. A. Spector and A. W. Norris Action of epoxyeicosatrienoic acids on cellular function Am J Physiol Cell Physiol, March 1, 2007; 292(3): C996 - C1012. [Abstract] [Full Text] [PDF]

				D. Nieves and J. J. Moreno Hydroxyeicosatetraenoic acids released through the cytochrome P-450 pathway regulate 3T6 fibroblast growth J. Lipid Res., December 1, 2006; 47(12): 2681 - 2689. [Abstract] [Full Text] [PDF]

				X. Fang, S. Hu, T. Watanabe, N. L. Weintraub, G. D. Snyder, J. Yao, Y. Liu, J. Y.-J. Shyy, B. D. Hammock, and A. A. Spector Activation of Peroxisome Proliferator-Activated Receptor {alpha} by Substituted Urea-Derived Soluble Epoxide Hydrolase Inhibitors J. Pharmacol. Exp. Ther., July 1, 2005; 314(1): 260 - 270. [Abstract] [Full Text] [PDF]

				X. Fang, N. L. Weintraub, R. B. McCaw, S. Hu, S. D. Harmon, J. B. Rice, B. D. Hammock, and A. A. Spector Effect of soluble epoxide hydrolase inhibition on epoxyeicosatrienoic acid metabolism in human blood vessels Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2412 - H2420. [Abstract] [Full Text] [PDF]

				T. L. Kaduce, X. Fang, S. D. Harmon, C. L. Oltman, K. C. Dellsperger, L. M. Teesch, V. R. Gopal, J. R. Falck, W. B. Campbell, N. L. Weintraub, et al. 20-Hydroxyeicosatetraenoic Acid (20-HETE) Metabolism in Coronary Endothelial Cells J. Biol. Chem., January 23, 2004; 279(4): 2648 - 2656. [Abstract] [Full Text] [PDF]

				J. R. Falck, U. M. Krishna, Y. K. Reddy, P. S. Kumar, K. M. Reddy, S. B. Hittner, C. Deeter, K. K. Sharma, K. M. Gauthier, and W. B. Campbell Comparison of vasodilatory properties of 14,15-EET analogs: structural requirements for dilation Am J Physiol Heart Circ Physiol, January 1, 2003; 284(1): H337 - H349. [Abstract] [Full Text] [PDF]

				X. Fang, N. L. Weintraub, C. L. Oltman, L. L. Stoll, T. L. Kaduce, S. Harmon, K. C. Dellsperger, C. Morisseau, B. D. Hammock, and A. A. Spector Human coronary endothelial cells convert 14,15-EET to a biologically active chain-shortened epoxide Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2306 - H2314. [Abstract] [Full Text] [PDF]

				G. D. Snyder, U. M. Krishna, J. R. Falck, and A. A. Spector Evidence for a membrane site of action for 14,15-EET on expression of aromatase in vascular smooth muscle Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1936 - H1942. [Abstract] [Full Text] [PDF]

				R. J. Roman P-450 Metabolites of Arachidonic Acid in the Control of Cardiovascular Function Physiol Rev, January 1, 2002; 82(1): 131 - 185. [Abstract] [Full Text] [PDF]

				D. E. Williard, S. D. Harmon, T. L. Kaduce, M. Preuss, S. A. Moore, M. E. C. Robbins, and A. A. Spector Docosahexaenoic acid synthesis from n-3 polyunsaturated fatty acids in differentiated rat brain astrocytes J. Lipid Res., September 1, 2001; 42(9): 1368 - 1376. [Abstract] [Full Text] [PDF]

				D. E. Williard, J. O. Nwankwo, T. L. Kaduce, S. D. Harmon, M. Irons, H. W. Moser, G. V. Raymond, and A. A. Spector Identification of a fatty acid {{Delta}}6-desaturase deficiency in human skin fibroblasts J. Lipid Res., April 1, 2001; 42(4): 501 - 508. [Abstract] [Full Text]

				X. Fang, T. L. Kaduce, N. L. Weintraub, S. Harmon, L. M. Teesch, C. Morisseau, D. A. Thompson, B. D. Hammock, and A. A. Spector Pathways of Epoxyeicosatrienoic Acid Metabolism in Endothelial Cells. IMPLICATIONS FOR THE VASCULAR EFFECTS OF SOLUBLE EPOXIDE HYDROLASE INHIBITION J. Biol. Chem., April 27, 2001; 276(18): 14867 - 14874. [Abstract] [Full Text] [PDF]