Stimulation of prostaglandin G/H synthase-2 expression by arachidonic acid monoxygenase product, 14,15-epoxyeicosatrienoic acid.
FEBS Lett
; 416(3): 269-72, 1997 Oct 27.
Article
em En
| MEDLINE
| ID: mdl-9373167
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Hidrocarboneto de Aril Hidroxilases
/
Regulação Enzimológica da Expressão Gênica
/
Prostaglandina-Endoperóxido Sintases
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Ácido 8,11,14-Eicosatrienoico
/
Oxigenases de Função Mista
/
Isoenzimas
Limite:
Animals
Idioma:
En
Ano de publicação:
1997
Tipo de documento:
Article