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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Downregulation of cytochrome P450 2C8 by 3-methylcholanthrene in human hepatocellular carcinoma cell lines
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Downregulation of cytochrome P450 2C8 by 3-methylcholanthrene in human hepatocellular carcinoma cell lines

机译:用3-甲基硫蒽醌中的细胞色素P450 2C8的下调在人肝细胞癌细胞系中

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摘要

The marked induction of cytochromes P450 such as CYP1A1 caused by polycyclic aromatic hydrocarbons (PAHs) like 3-methylcholanthrene (MC) is often accompanied by suppression of other hepatic P450s. The molecular mechanisms, functional consequences, and human relevance of P450 downregulation by PAHs are poorly understood. MC suppresses mRNA levels for CYP2C8, an important human P450, in cultured human hepatocytes. To avoid hepatocyte lot-to-lot variability, we assessed CYP2C8 regulation by MC in HepaRG cells, a terminally differentiated human hepatocellular carcinoma cell line that maintains high P450 expression. MC strongly induced CYP1A1 mRNA levels and markedly downregulated CYP2C8 mRNA levels in HepaRG cells. Although MC also suppressed CYP2C8 mRNA levels in the HepG2 human hepatocellular carcinoma cell line, basal CYP2C8 expression was extremely low. HepaRG cells appear to be an appropriate model system for studying the mechanisms and functional consequences of CYP2C8 downregulation by PAHs.
机译:由多环芳族烃(PAH)如3-甲基蒽(MC)相同的CYP1A1如CYP1A1的标记诱导通常伴随抑制其他肝P450s。 P450通过PAHS下调的分子机制,功能后果和人的相关性差不多清楚。 MC抑制CYP2C8的mRNA水平,培养的人肝细胞中的重要人体P450。为了避免肝细胞批量变异性,我们通过MC在肝细胞中评估CYP2C8调节,终端分化的人肝细胞癌细胞系,保持高P450表达。 MC强烈诱导的CYP1A1 mRNA水平并明显下调肝细胞中的CYP2C8 mRNA水平。虽然MC还抑制了HepG2人肝细胞癌细胞系中的CYP2C8 mRNA水平,但基础CYP2C8表达极低。肝细胞似乎是研究CYP2C8下调的机制和功能后果的适当模型系统。

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