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Gene structure of CYP2C8 and extrahepatic distribution of the human CYP2Cs.

机译:CYP2C8的基因结构和人CYP2Cs的肝外分布。

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Extrahepatic tissue distribution of the mRNAs for the four human CYP2Cs (2C8, 2C9, 2C18, and 2C19) was examined in kidney, testes, adrenal gland, prostate, brain, uterus, mammary gland, ovary, lung, and duodenum. CYP2C mRNAs were detected by RT-PCR using specific primers for each individual CYP2C. CYP2C8 mRNA was detected in the kidney, adrenal gland, brain, uterus, mammary gland, ovary, and duodenum. CYP2C9 mRNA was detected in the kidney, testes, adrenal gland, prostate, ovary, and duodenum. CYP2C18 mRNA was found only in the brain, uterus, mammary gland, kidney, and duodenum and CYP2C19 mRNA was found only in the duodenum. Immunoblot analysis of small intestinal microsomes detected both 2C9 and 2C19 proteins. In addition, genomic clones for CYP2C8 were sequenced, and long-distance PCR was performed to determine the complete gene structure. CYP2C8 spanned a 31 kb region. Comparative analysis of the 2.4 kb upstream region of CYP2C8 with CYP2C9 revealed two previously unidentified transcription factors sites, C/EBP and HPF-1, and the latter might be involved in hepatic expression. Although CYP2C8 has been shown to be phenobarbital inducible, neither a barbiturate-responsive regulatory sequence (a Barbie box) nor a phenobarbital-responsive enhancer module (PBREM) was found within the upstream region analyzed.
机译:在肾脏,睾丸,肾上腺,前列腺,脑,子宫,乳腺,卵巢,肺和十二指肠中检查了四种人类CYP2C(2C8、2C9、2C18和2C19)mRNA的肝外组织分布。 CYP2C mRNAs通过RT-PCR使用特定的引物针对每个单独的CYP2C进行检测。在肾脏,肾上腺,脑,子宫,乳腺,卵巢和十二指肠中检测到CYP2C8 mRNA。在肾脏,睾丸,肾上腺,前列腺,卵巢和十二指肠中检测到CYP2C9 mRNA。 CYP2C18 mRNA仅在脑,子宫,乳腺,肾脏和十二指肠中发现,CYP2C19 mRNA仅在十二指肠中发现。小肠微粒体的免疫印迹分析检测到2C9和2C19蛋白。另外,对CYP2C8的基因组克隆进行测序,并进行长距离PCR以确定完整的基因结构。 CYP2C8跨度为31 kb。对CYP2C8的2.4 kb上游区域与CYP2C9进行比较分析,发现两个以前未鉴定的转录因子位点C / EBP和HPF-1,后者可能参与肝表达。尽管已显示CYP2C8是苯巴比妥可诱导的,但在所分析的上游区域内未发现巴比妥酸盐反应性调节序列(芭比盒)或苯巴比妥反应性增强模块(PBREM)。

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