Study on the transcriptional modulation of cytochrome P450 3A4 expression by zearalenone / 中华预防医学杂志
Chinese Journal of Preventive Medicine
;
(12): 411-414, 2004.
Artigo
em Chinês
| WPRIM
| ID: wpr-299214
ABSTRACT
<p><b>OBJECTIVE</b>To study whether zearalenone (ZEA), a fungal estrogen, can transcriptionally up-regulate the expression of cytochrome 450 3A4 (CYP3A4) transcription by activating human steroid hormone and xenobiotic receptor (SXR).</p><p><b>METHOD</b>Transient cotransfection reporter gene assays were performed with human SXR expression plasmid and a reporter plasmid containing the SXR in the CYP3A4 gene promoter in HepG(2) cells.</p><p><b>RESULTS</b>The transcriptional induction of CYP3A4 by ZEA with a dose, time-dependent manner. ZEA at the concentrations of 0.01, 0.10, 1.00 and 10.00 micromol/L, respectively, could induce CYP3A4 with (1.50 +/- 0.21), (1.66 +/- 0.27), (3.04 +/- 0.82) and (3.96 +/- 1.16) folds, as compared with 0.1% DMSO. Results from a time-dependent study show that 1.00 and 10.00 micromol/L of ZEA for 12 to 48 hours could enhance the transcription of CYP3A4 with (3.69 +/- 1.34) and (5.18 +/- 1.50) folds, and 10.00 micromol/L of ZEA for 48 hours could induce the CYP3A4 gene expression (5.18 +/- 1.50) folds, as compared with 0.1% DMSO by activating human SXR.</p><p><b>CONCLUSION</b>ZEA could induce the expression of the CYP3A4 gene transcription through activating SXR, possibly by affecting the other substrates of the CYP3A4, especially affecting the metabolism of drugs in the body.</p>
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Patologia
/
Farmacologia
/
Transcrição Gênica
/
Zearalenona
/
Células Tumorais Cultivadas
/
Genes Reporter
/
Carcinoma Hepatocelular
/
Sistema Enzimático do Citocromo P-450
/
Citocromo P-450 CYP3A
/
Genética
Limite:
Humanos
Idioma:
Chinês
Revista:
Chinese Journal of Preventive Medicine
Ano de publicação:
2004
Tipo de documento:
Artigo
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