Post-transcriptional regulation of coumarin 7-hydroxylase (P450coh) induction by xenobiotics in mouse liver: mRNA stabilization by pyrazole

Conference · Fri Mar 15 00:00:00 EST 1991 · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)

OSTI ID:5238981

Aida, K; Negishi, M ^[1]

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1. NIEHS/NIH, Research Triangle Park, NC (United States)

The induction mechanism by pyrazole or phenobarbital of coumarin 7-hydroxylase was investigated in DBA/2J male mice. The P450coh mRNA in the pyrazole-induced mice was increased gradually to a 20-fold higher level within 48 hr, yet transcription of the P450coh gene was not affected. The half-life of P450coh mRNA, on the other hand, was at least 4-fold longer in the pyrazole-induced DBA2J than in control DBA/2J male mice. The stabilization of P450coh mRNA, therefore, is the primary mechanism for the induction by pyrazole of coumarin 7-hydroxylase. Phenobarbital, on the other hand, regulates the induction translationally or post-translationally. This drug affected neither the P450coh mRNA nor the P450coh gene's transcription levels in the DBA/2J male mice, although Western blots showed a 2- to 3-fold increase of the P450coh protein in the liver microsomes of the drug-treated mice. The results indicate, therefore, that both phenobarbital and pyrazole regulate the P450coh induction post-transcriptional efficiency of P450coh mRNA or alters the degradation rate of P450coh protein, while the latter stabilizes P450coh mRNA.

• OSTI ID: 5238981
• Report Number(s): CONF-9104107-; CODEN: FAJOE
• Journal Information: FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Vol. 5:5; Conference: 75. annual meeting of the Federation of American Societies for Experimental Biology (FASEB), Atlanta, GA (United States), 21-25 Apr 1991; ISSN 0892-6638
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
HYDROXYLASES
GENE REGULATION
PHENOBARBITAL
BIOLOGICAL EFFECTS
PYRAZOLES
COUMARIN
ENZYME INDUCTION
LIVER
MESSENGER-RNA
MICE
POST-TRANSLATION MODIFICATION
ANESTHETICS
ANIMALS
ANTICONVULSANTS
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AZOLES
BARBITURATES
BODY
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DIGESTIVE SYSTEM
DRUGS
ENZYMES
ESTERS
GLANDS
HETEROCYCLIC COMPOUNDS
HYPNOTICS AND SEDATIVES
LACTONES
MAMMALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
OXIDOREDUCTASES
PROTEINS
PYRANS
PYRIMIDINES
RNA
RODENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology