Assessment of human pregnane X receptor involvement in pesticide-mediated activation of CYP3A4 gene.
作者： Tsutomu Matsubara , Wachiraporn Noracharttiyapot , Takayoshi Toriyabe , Kouichi Yoshinari , Kiyoshi Nagata
关键词: Cytochrome P450 、 Pregnane X receptor 、 CYP3A4 、 Endogeny 、 Isozyme 、 Molecular biology 、 Gene 、 Activator (genetics) 、 Enhancer 、 Biology
摘要: Assessment of foreign chemical inducibility on CYP3A4 is necessary to optimize drug therapies. The properties chemicals such as pesticides, however, are not well investigated. In the present study, various pesticides human induction have been tested using HepG2-derived cells stably expressing promoter/enhancer (3-1-10 cells) and pregnane X receptor (hPXR)-small interfering RNA (siRNA) system. Among examined 13 were observed activate gene. Surprisingly, pyributicarb was found increase reporter activity at 0.1 1 μM more strongly than typical inducer rifampicin. Expression hPXR-siRNA clearly diminished pyributicarb-stimulated in 3-1-10 decreased endogenous mRNA levels HepG2 cells. Pyributicarb caused enhancement CYP3A4-derived mouse livers introduced with hPXR by adenovirus. These results indicate a potent activator gene, suggesting existence leading our environment.
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