Tissue Distribution and Gender-Specific Protein Expression of Cytochrome P450 in five Mouse Genotypes with a Background of FVB
Tissue Distribution and Gender-Specific Protein Expression of Cytochrome P450 in five Mouse Genotypes with a Background of FVB
复制标题
具有 FVB 背景的五种小鼠基因型中 CYP450 的组织分布和性别特异性蛋白表达
DOI：
10.1007/s11095-018-2389-2
复制
发表时间：
2018-06-01
影响因子：
3.7
通讯作者：
Liu, Zhongqiu Q.
中科院分区：
文献类型：
--
作者：
Chen, Jiamei M.;Zhang, Qisong S.;Liu, Zhongqiu Q.
目的系统研究细胞色素P450 （Cyps）在Friend病毒B （FVB）背景下5种基因型小鼠的组织分布和性别特异性蛋白表达。方法从主要代谢器官组织S9部分提取Cyps，采用UHPLC-MS/MS法进行绝对定量。结果Cyps在肝脏中表达量最高，其次为小肠和肾脏。在肝脏中，Cyp1a2、Cyp2c29、Cyp2c39、Cyp2d22、Cyp2e1和Cyp3a11是主要亚型。Cyp1a2和Cyp2c29是男性特异性的，而Cyp2c39是女性特异性的。与野生型（WT） FVB小鼠相比，雌性外排转运体（ET）敲除小鼠Cyp1a2、Cyp1b1、Cyp2d22和Cyp3a25的表达显著降低。在小肠中，Cyp2c29和Cyp3a11是主要的亚型。敲除ET并未改变大多数Cyps的表达水平。然而，雌性ET敲除小鼠的Cyp2c29表达高于WT FVB小鼠。除Bcrp1（-/-）小鼠外，ET敲除小鼠中Cyp7a1的表达明显降低。在肾脏中，Cyp2e1是主要亚型，并表现出男性特异性。敲除ET对Cyps在脑、心、肺、脾和胃中的蛋白表达有轻微影响。结论全面了解WT和ET敲除FVB小鼠主要代谢器官中Cyps的分布特征和性别特异性表达，有助于更好地了解药物的疗效和毒性，以及药物-药物相互作用。
Purpose To systematically investigate tissue distribution and gender-specific protein expression of Cytochrome P450 (Cyps) in five mouse genotypes with a background of Friend virus B (FVB).Methods The Cyps were extracted from the tissue S9 fractions of the main metabolic organs and then absolutely quantified by applying the UHPLC-MS/MS method.Results The liver had the highest expression of Cyps, followed by the small intestine and kidney. In the liver, Cyp1a2, Cyp2c29, Cyp2c39, Cyp2d22, Cyp2e1, and Cyp3a11 were the main isoforms. Cyp1a2 and Cyp2c29 were male-specific, while Cyp2c39 was female-specific. Compared with the expression in Wild-type (WT) FVB mice, the expression of Cyp1a2, Cyp1b1, Cyp2d22, and Cyp3a25 significantly decreased in female efflux transporter (ET) knockout mice. In the small intestine, Cyp2c29 and Cyp3a11 were the major isoforms. Knockout of ET didn't alter the expression levels of most Cyps. However, female ET knockout mice presented higher Cyp2c29 expression than WT FVB mice. The Cyp7a1 expression was markedly decreased in ET knockout mice except Bcrp1(-/-) mice. In the kidney, Cyp2e1 was the main isoform and exhibited male specificity. Knockout of ET slightly affected the protein expression of Cyps in the brain, heart, lung, spleen and stomach.Conclusions A comprehensive understanding of the distribution characteristics and gender-specific expression of Cyps in major metabolic organs of WT and ET knockout FVB mice should contribute to a better understanding of drug efficacy and toxicity, and drug-drug interactions.