| Summary: | 碩士 === 國立成功大學 === 藥理學研究所 === 100 === People without CYP3A5 expression was supposed to have a higher plasma concentration and lower clearance of drugs. However, our laboratory previously showed that CYP3A5*3 genotype affects the protein level of CYP3A5 but does not influence the midazolam metabolism in clinical data. Recent studies have demonstrated that CYP3A5*1/*3 (positive) male subjects exhibited a higher nifedipine (immediate-release form, Adalat® ) plasma concentration than CYP3A5*3/*3 (negative) male subjects but not for female subjects on slow-release nifedipine administrate. CYP3A4 level seemed to be up-regulated in some of homozygous CYP3A5*3 subjects. In human CYP3A4-transgenic (Tg-CYP3A4) mice, overexpression of CYP3A4 enhanced estradiol metabolism. Upregulation of estradiol metabolism decreased CYP3A4 by feedback inhibition. From above, CYP3A4 expression level was affected by CYP3A5 and estradiol. Therefore we want to study the role of CYP3A5 and estraiol in drug metabolism and expression level of CYP3A4. In this study CYP3A4 protein level was not affected by treating with estradiol or CYP3A5 overexpression in Caco-2 and HepG2 cells. Interestingly, CYP3A4 protein level was affeced by CYP3A5 overexpression cells together with various concentrations of estradiol. Moreover, previous studies show that 1 alpha,25-(OH)2-D3, vitamin D receptor (VDR) ligand, promotes CYP3A4 expression. In order to study the effect of CYP3A5, we observed CYP3A4 expression level affected by cotreatment of estradiol and VDR ligand in CYP3A5 overexpression cells. Above data indicate that CYP3A5 affect CYP3A4 expression level under the circumstances.
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