20-Carboxy-arachidonic acid is a dual activator of peroxisome proliferator-activated receptors α and γ

Xiang Fang; Joseph S Dillon; Shanming Hu; Shawn D Harmon; Jianrong Yao; Siddam Anjaiah; J.R Falck; Arthur A Spector

doi:10.1016/j.prostaglandins.2006.05.002

Back

20-Carboxy-arachidonic acid is a dual activator of peroxisome proliferator-activated receptors α and γ

Journal article

Peer reviewed

20-Carboxy-arachidonic acid is a dual activator of peroxisome proliferator-activated receptors α and γ

Xiang Fang, Joseph S Dillon, Shanming Hu, Shawn D Harmon, Jianrong Yao, Siddam Anjaiah, J.R Falck and Arthur A Spector

Prostaglandins & other lipid mediators, Vol.82(1), pp.175-184

2007

DOI: 10.1016/j.prostaglandins.2006.05.002

PMID: 17164145

View Online

Abstract

20-Carboxy-arachidonic acid (20-COOH-AA) is a metabolite of 20-hydroxyeicosatetraenoic acid (20-HETE), an eicosanoid produced from arachidonic acid by cytochrome P450 (CYP) ω-oxidases. Alcohol dehydrogenases convert 20-HETE to 20-COOH-AA, and we now find that a microsomal preparation containing recombinant human CYP4F3B converts arachidonic acid to 20-HETE and 20-COOH-AA. Studies with transfected COS-7 cell expression systems indicate that 20-COOH-AA activates peroxisome proliferators-activated receptor (PPAR) α and PPARγ. 20-COOH-AA was twice as potent as either 20-HETE or ciglitazone in stimulating PPARγ-mediated luciferase expression. While 20-COOH-AA also was more potent than 20-HETE in increasing PPARα-mediated luciferase expression, the increase was only half as much as that produced by Wy-14643. 20-COOH-AA did not increase PPARα or PPARγ expression in the transfected cells. Radiolabeled 20-COOH-AA was detected intracellularly when the COS-7 cells were incubated with either [ 3H]20-COOH-AA or [ 3H]20-HETE, and binding studies indicated that [ 3H]20-COOH-AA bound to the isolated ligand binding domains of PPARα ( K d = 0.87 ± 0.12 μM) and PPARγ ( K d = 1.7 ± 0.5 μM). These findings suggest that 20-COOH-AA, a relatively stable metabolite of 20-HETE, might function as an endogenous dual activator of PPARα and PPARγ.

ω-Oxidation

20-HETE

Arachidonic acid

Nuclear receptors

Cytochrome P450

Details

Title: Subtitle: 20-Carboxy-arachidonic acid is a dual activator of peroxisome proliferator-activated receptors α and γ
Creators: Xiang Fang - Department of Biochemistry, 4-403 BSB, University of Iowa Carver College of Medicine, Iowa City, IA 52242, United States
Joseph S Dillon - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, United States
Shanming Hu - Department of Biochemistry, 4-403 BSB, University of Iowa Carver College of Medicine, Iowa City, IA 52242, United States
Shawn D Harmon - Department of Biochemistry, 4-403 BSB, University of Iowa Carver College of Medicine, Iowa City, IA 52242, United States
Jianrong Yao - Department of Biochemistry, 4-403 BSB, University of Iowa Carver College of Medicine, Iowa City, IA 52242, United States
Siddam Anjaiah - Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
J.R Falck - Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
Arthur A Spector - Department of Biochemistry, 4-403 BSB, University of Iowa Carver College of Medicine, Iowa City, IA 52242, United States
Resource Type: Journal article
Publication Details: Prostaglandins & other lipid mediators, Vol.82(1), pp.175-184
Publisher: Elsevier Inc
DOI: 10.1016/j.prostaglandins.2006.05.002
PMID: 17164145
ISSN: 1098-8823
Language: English
Date published: 2007
Academic Unit: Stead Family Department of Pediatrics; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984094773402771

Metrics

26 Record Views

34 Times Cited - Web of Science