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Stimulation of prostaglandin G/H synthase‐2 expression by arachidonic acid monoxygenase product, 14,15‐epoxyeicosatrienoic acid
Author(s) -
Peri Krishna G.,
Varma Daya R.,
Chemtob Sylvain
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01227-1
Subject(s) - epoxygenase , arachidonic acid , epoxyeicosatrienoic acid , epoxide hydrolase 2 , prostaglandin , biology , stimulation , biochemistry , chemistry , microbiology and biotechnology , endocrinology , enzyme
The relationship between arachidonic acid (AA) mobilization and transcription of immediate‐early genes, particularly of prostaglandin G/H synthase‐2 (PGHS‐2), in intestinal crypt epithelial cells was analyzed. PGHS‐2 mRNA and protein synthesis were stimulated by its own substrate, AA; actinomycin D, a transcription inhibitor, prevented the AA‐induced increase in PGHS‐2 mRNA. Eicosatetraynoic acid, an inhibitor of AA utilization, significantly reduced PGHS‐2 mRNA synthesis elicited by AA. Inhibitors of cytochrome P450 monoxygenases, ketoconazole and miconazole, also prevented PGHS‐2 mRNA synthesis in a dose‐dependent manner. Phenyl chalcone oxide, an epoxide hydrolase inhibitor, potentiated AA‐induced PGHS‐2 mRNA synthesis. Of the four regioisomers of arachidonic acid epoxides, only 14,15‐epoxyeicosatrienoic acid elicited the expression of PGHS‐2 in intestinal crypt epithelial cells. This is the first direct evidence of stimulation of an immediate‐early gene product, specifically PGHS‐2, by an AA epoxygenase metabolite, 14,15‐epoxyeicosatrienoic acid, as well as of a heterologous regulation of PGHS‐2 synthesis by these monoxygenase products.