Modulation of MDR1 and CYP3A expression by dexamethasone: evidence for an inverse regulation in adrenals.

Sérée, E; Villard, P H; Hevér, A; Guigal, N; Puyoou, F; Charvet, B; Point-Scomma, H; Lechevalier, E; Lacarelle, B; Barra, Y

Sérée, E; Villard, P H; Hevér, A; Guigal, N; Puyoou, F; Charvet, B; Point-Scomma, H; Lechevalier, E; Lacarelle, B; Barra, Y.

Afiliación

Sérée E; UPRES-A CNRS 6032, EA 2194 Laboratory of Toxicology, Mediterranean University, 27 Boulevard J Moulin, Marseille, 13385, France. eric.seree@pharmacie.univ-mrs.fr

Biochem Biophys Res Commun ; 252(2): 392-5, 1998 Nov 18.

Article en En | MEDLINE | ID: mdl-9826540

RESUMEN

A strong overlap exists between gp170 and CYP3A substrates and inducers. In order to investigate a putative coregulation of MDR and CYPA gene expression, we measured their transcripts in human liver and after dexamethasone treatment in HepG2 cells or in different mouse tissues. In human liver, we observed no correlation between MDR1 and CYP3A4 expression, whereas these genes were coinduced by dexamethasone in HepG2 cells. In mouse liver treated with dexamethasone, mdr1b and Cyp3a were induced (5- and 2-fold, respectively). In adrenals, the main expressing gp170 tissue, Cyp3a, was increased while mdr1b was repressed (-51%). The expression of mdr1b increased in heart, brain, and colon and decreased in lung and kidney but Cyp3a was not detectable. In conclusion, human hepatic CYP3A4 and MDR1 are not corregulated but are coinducible. In vivo murine mdr1b and Cyp3a are coregulated by dexamethasone in liver and inversely regulated in adrenals.

Asunto(s)

Glándulas Suprarrenales/efectos de los fármacos; Glándulas Suprarrenales/metabolismo; Hidrocarburo de Aril Hidroxilasas; Sistema Enzimático del Citocromo P-450/genética; Dexametasona/farmacología; Genes MDR/efectos de los fármacos; Oxidorreductasas N-Desmetilantes/genética; Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/biosíntesis; Animales; Secuencia de Bases; Línea Celular; Citocromo P-450 CYP3A; Sistema Enzimático del Citocromo P-450/biosíntesis; Cartilla de ADN/genética; Inducción Enzimática/efectos de los fármacos; Expresión Génica/efectos de los fármacos; Humanos; Técnicas In Vitro; Hígado/efectos de los fármacos; Hígado/metabolismo; Ratones; Oxidorreductasas N-Desmetilantes/biosíntesis; ARN Mensajero/genética; ARN Mensajero/metabolismo; Reacción en Cadena de la Polimerasa de Transcriptasa Inversa; Distribución Tisular

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oxidorreductasas N-Desmetilantes / Dexametasona / Hidrocarburo de Aril Hidroxilasas / Glándulas Suprarrenales / Genes MDR / Sistema Enzimático del Citocromo P-450 Límite: Animals / Humans Idioma: En Revista: Biochem Biophys Res Commun Año: 1998 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos

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