Journal article
14,15-Epoxyeicosatrienoic acid inhibits prostaglandin E2 production in vascular smooth muscle cells
American journal of physiology. Heart and circulatory physiology, Vol.275(6), pp.H2113-H2121
12/01/1998
DOI: 10.1152/ajpheart.1998.275.6.H2113
PMID: 9843811
Abstract
14,15-Epoxyeicosatrienoic acid (EET), a cytochrome P-450 epoxygenase product of arachidonic acid (AA), reduced PGE2 formation by 40–75% in porcine aortic and murine brain microvascular smooth muscle cells. The inhibition was reversed 6–10 h after removal of 14,15-EET from the medium and was regioisomeric specific; 8,9-EET produced a smaller effect, whereas 11,12- and 5,6-EET were ineffective. Although the cells converted 14,15-EET to 14,15-dihydroxyeicosatrienoic acid (14,15-DHET), 14,15-DHET did not inhibit PGE2formation, and the 14,15-EET-induced inhibition was potentiated by 4-phenylchalcone oxide, an epoxide hydrolase inhibitor. The inhibition occurred when substrate amounts of AA were used and was not accompanied by enhanced production of other PGs, suggesting an effect on PGH synthase; however, in murine cells, 14,15-EET did not reduce PGH synthase mRNA or protein. Moreover, the 14,15-EET-induced decrease in PGE2 production was overcome by increasing the concentration of AA, but not oleic acid (which is not a substrate for PGH synthase). These findings suggest that 14,15-EET competitively inhibits PGH synthase activity in vascular smooth muscle cells. The 14,15-EET-induced inhibition of PGE2 production resulted in potentiation of platelet-derived growth factor-induced smooth muscle cell proliferation, suggesting that the competitive inhibition of PGH synthase by 14,15-EET can affect growth responses in smooth muscle cells.
Details
- Title: Subtitle
- 14,15-Epoxyeicosatrienoic acid inhibits prostaglandin E2 production in vascular smooth muscle cells
- Creators
- Xiang Fang - Departments of BiochemistrySteven A Moore - PathologyLynn L Stoll - Anesthesia, andGretchen Rich - PathologyTerry L Kaduce - Departments of BiochemistryNeal L Weintraub - Internal Medicine, College of Medicine, University of Iowa, Iowa City, Iowa 52242Arthur A Spector - Departments of Biochemistry,, Internal Medicine, College of Medicine, University of Iowa, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.275(6), pp.H2113-H2121
- DOI
- 10.1152/ajpheart.1998.275.6.H2113
- PMID
- 9843811
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Language
- English
- Date published
- 12/01/1998
- Academic Unit
- Pathology; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984047686202771
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