20-hydroxyeicosatetraenoic acid (20-HETE) metabolism in coronary endothelial cells

Terry L Kaduce; Xiang Fang; Shawn D Harmon; Christine L Oltman; Kevin C Dellsperger; Lynn M Teesch; V Raj Gopal; J R Falck; William B Campbell; Neal L Weintraub; Arthur A Spector

doi:10.1074/jbc.M306849200

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20-hydroxyeicosatetraenoic acid (20-HETE) metabolism in coronary endothelial cells

Journal article

Open access

Peer reviewed

20-hydroxyeicosatetraenoic acid (20-HETE) metabolism in coronary endothelial cells

Terry L Kaduce, Xiang Fang, Shawn D Harmon, Christine L Oltman, Kevin C Dellsperger, Lynn M Teesch, V Raj Gopal, J R Falck, William B Campbell, Neal L Weintraub, …

The Journal of biological chemistry, Vol.279(4), pp.2648-2656

01/23/2004

DOI: 10.1074/jbc.M306849200

PMID: 14612451

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Abstract

We have investigated the role of endothelial cells in the metabolism of 20-hydroxyeicosatetraenoic acid (20-HETE), a vasoactive mediator synthesized from arachidonic acid by cytochrome P450 omega-oxidases. Porcine coronary artery endothelial cells (PCEC) incorporated 20-[(3)H]HETE primarily into the sn-2 position of phospholipids through a coenzyme A-dependent process. The incorporation was reduced by equimolar amounts of arachidonic, eicosapentaenoic or 8,9-epoxyeicosatrienoic acids, but some uptake persisted even when a 10-fold excess of arachidonic acid was available. The retention of 20-[(3)H]HETE increased substantially when methyl arachidonoyl fluorophosphonate, but not bromoenol lactone, was added, suggesting that a Ca(2+)-dependent cytosolic phospholipase A(2) released the 20-HETE contained in PCEC phospholipids. Addition of calcium ionophore A23187 produced a rapid release of 20-[(3)H]HETE from the PCEC, a finding that also is consistent with a Ca(2+)-dependent mobilization process. PCEC also converted 20-[(3)H]HETE to 20-carboxy-arachidonic acid (20-COOH-AA) and 18-, 16-, and 14-carbon beta-oxidation products. 20-COOH-AA produced vasodilation in porcine coronary arterioles, but 20-HETE was inactive. These results suggest that the incorporation of 20-HETE and its subsequent conversion to 20-COOH-AA in the endothelium may be important in modulating coronary vascular function.

Animals

Biological Transport, Active - drug effects

Calcimycin - pharmacology

Coronary Vessels - metabolism

Endothelium, Vascular - metabolism

Hydroxyeicosatetraenoic Acids - metabolism

Ionophores - pharmacology

Swine

Time Factors

Details

Title: Subtitle: 20-hydroxyeicosatetraenoic acid (20-HETE) metabolism in coronary endothelial cells
Creators: Terry L Kaduce - University of Iowa
Xiang Fang - University of Iowa
Shawn D Harmon - University of Iowa
Christine L Oltman - University of Iowa
Kevin C Dellsperger - University of Missouri
Lynn M Teesch - University of Iowa
V Raj Gopal - The University of Texas Southwestern Medical Center
J R Falck - The University of Texas Southwestern Medical Center
William B Campbell - Medical College of Wisconsin
Neal L Weintraub - University of Iowa
Arthur A Spector - University of Iowa
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.279(4), pp.2648-2656
DOI: 10.1074/jbc.M306849200
PMID: 14612451
ISSN: 0021-9258
eISSN: 1083-351X
Grant note: HL62984 / NHLBI NIH HHS HL51055 / NHLBI NIH HHS HL070860 / NHLBI NIH HHS RR13799 / NCRR NIH HHS HL72845 / NHLBI NIH HHS GM31278 / NIGMS NIH HHS
Language: English
Date published: 01/23/2004
Academic Unit: Core Research Facilities; Biochemistry and Molecular Biology; Medicine Administration; Internal Medicine
Record Identifier: 9984622755502771

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