Stimulation of prostaglandin G/H synthase‐2 expression by arachidonic acid monoxygenase product, 14,15‐epoxyeicosatrienoic acid

FEBS Letters

Peri, Krishna G.¹  Chemtob, Sylvain¹  Varma, Daya R.² 

[1] Research Center, Ste. Justine Hospital, 3175 Cote Ste. Catherine, Montreal H3T 1C5, Canada;Department of Pharmacology and Experimental Therapeutics, McGill University, 3655 Drummond St., Montreal H3G 1Y3, Canada

关键词: Prostaglandin G/H synthase-2;    Prostaglandin synthesis;    Arachidonic acid;    Cytochrome P450 monoxygenase;    Gene transcription;    Epoxyeicosatrienoic acid;    PGHS;    prostaglandin G/H synthase;    ETYA;    eicosatetraynoic acid;    EET;    epoxyeicosatrienoic acid;    PG;    prostaglandin;    AA;    arachidonic acid;   

DOI  :  10.1016/S0014-5793(97)01227-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown