与CYP3A5、CYP3A7和CYP3A43相比，药物诱导的人CYP3A4 mRNA表达差异。
Differential drug-induced mRNA expression of human CYP3A4 compared to CYP3A5, CYP3A7 and CYP3A43.
作者信息
Krusekopf Solveigh, Roots Ivar, Kleeberg Ullrich
机构信息
Institute of Clinical Pharmacology, Charité, Humboldt University of Berlin, Schumannstr. 20/21, D-10098, Berlin, Germany.
出版信息
Eur J Pharmacol. 2003 Apr 11;466(1-2):7-12. doi: 10.1016/s0014-2999(03)01481-x.
Drug-mediated regulation of mRNA expression of all members of the cytochrome P450 3A (CYP3A) subfamily has been measured by reverse transcription-polymerase chain reaction (RT-PCR) in the human hepatocellular carcinoma cell line, HepG2. Transcriptional regulation was proved by inhibition of induction with actinomycin D. Besides the positive control dexamethasone, the H(+)/K(+)-ATPase inhibitors omeprazole, lansoprazole, pantoprazole, and rabeprazole, and the herbal antidepressant St. John's wort (Hypericum extract) were studied. All CYP3A mRNAs were induced by dexamethasone. CYP3A4 was the only CYP3A isoform that was induced by all of the four benzimidazole derivatives, while CYP3A5, CYP3A7, and CYP3A43 were unaffected or even slightly downregulated by these drugs. St. John's wort also increased CYP3A4 mRNA exclusively, leaving CYP3A5 and CYP3A43 unaffected, whereas CYP3A7 was decreased. Depending on the inducer, expression of CYP3A4 is differently regulated from CYP3A5, CYP3A7, and CYP3A43.
在人肝癌细胞系HepG2中，已通过逆转录-聚合酶链反应（RT-PCR）测定了细胞色素P450 3A（CYP3A）亚家族所有成员的药物介导的mRNA表达调控。通过放线菌素D抑制诱导作用证明了转录调控。除了阳性对照地塞米松外，还研究了H(+)/K(+)-ATP酶抑制剂奥美拉唑、兰索拉唑、泮托拉唑和雷贝拉唑，以及草药抗抑郁药圣约翰草（金丝桃提取物）。所有CYP3A mRNA均被地塞米松诱导。CYP3A4是唯一被所有四种苯并咪唑衍生物诱导的CYP3A同工型，而CYP3A5、CYP3A7和CYP3A43不受这些药物影响，甚至略有下调。圣约翰草也仅增加CYP3A4 mRNA，而CYP3A5和CYP3A43不受影响，而CYP3A7则减少。根据诱导剂的不同，CYP3A4的表达与CYP3A5、CYP3A7和CYP3A43的调控方式不同。
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