Cytochrome P450 3A expression and function in liver and intestinal mucosa from dexamethasone-treated sheep
The effects of repeated administrations of dexamethasone (DEX) (3mg/kg/day by IM route for 7days) on the gene expression profile of a cytochrome P450 (CYP) 3A28-like isoenzyme, on the expression of a CYP3A-immunoreactive protein and on CYP3A-dependent metabolic activities in sheep liver and small in...
| Autores: | , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2012 |
| País: | Argentina |
| Institución: | Consejo Nacional de Investigaciones Científicas y Técnicas |
| Repositorio: | CONICET Digital (CONICET) |
| Idioma: | inglés |
| OAI Identifier: | oai:ri.conicet.gov.ar:11336/83884 |
| Acceso en línea: | http://hdl.handle.net/11336/83884 |
| Access Level: | acceso abierto |
| Palabra clave: | Cytochrome P450 3a Expression Dexamethasone Sheep https://purl.org/becyt/ford/4.3 https://purl.org/becyt/ford/4 |
| Sumario: | The effects of repeated administrations of dexamethasone (DEX) (3mg/kg/day by IM route for 7days) on the gene expression profile of a cytochrome P450 (CYP) 3A28-like isoenzyme, on the expression of a CYP3A-immunoreactive protein and on CYP3A-dependent metabolic activities in sheep liver and small intestinal mucosa were evaluated in the current work. CYP 3A-dependent metabolic activities (erythromycin and triacetyl-oleandomycin N-demethylations) were assessed in microsomal fractions. The mRNA expression of CYP3A28-like, glucocorticoid receptor, constitutive androstane receptor, pregnane X receptor and retinoic X receptor alpha (RXRα) was determined by quantitative real-time PCR. The expression of a CYP3A-immunoreactive protein was measured by Western blot analyses. In the liver, DEX treatment increased CYP3A28-like mRNA levels (2.67-fold, P<0.01) and CYP3A apoprotein expression (1.34-fold, P<0.05) and stimulated CYP3A-dependent metabolism. High and significant correlation coefficients between CYP3A-dependent activities and CYP3A28-like gene (r=0.835-0.856, P<0.01) or protein (r=0.728-0.855, P<0.05) expression profiles were observed. Among the transcriptional factors, DEX only stimulated (2.1-fold, P<0.01) the mRNA expression of RXRα. In sheep small intestine, DEX caused a slight increment (34.6%, P<0.05) in erythromycin N-demethylase activity in the jejunal mucosa and a significant enhancement (P<0.05) of CYP3A apoprotein level in the duodenal mucosa. |
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