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狨猴肝脏细胞色素P450:其cDNA的表达及分子克隆研究

Marmoset liver cytochrome P450s: study for expression and molecular cloning of their cDNAs.

作者信息

Igarashi T, Sakuma T, Isogai M, Nagata R, Kamataki T

机构信息

Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.

出版信息

Arch Biochem Biophys. 1997 Mar 1;339(1):85-91. doi: 10.1006/abbi.1996.9852.

Abstract

Northern blot and immunoblot analyses indicated that considerable levels of CYP2B, CYP2C, CYP2D, CYP2E, and CYP3A were expressed in the liver of untreated marmosets. CYP1A was also expressed but to lesser extents. CYP3A mRNA was also detectable in the small intestine of untreated marmoset; the amount was increased by treatment with polychlorinated biphenyl. From a liver cDNA library, two cDNA clones coding for CYP2D19 and CYP3A21 (clones CM2D-1 and CM3A-10, respectively) were isolated. CM2D-1 and CM3A-10 contained an entire coding region for polypeptide 497 and 503 amino acid residues, respectively. The deduced amino acid sequences of CYP2D19 and CYP3A21 showed 90% identities to human CYP2D6 and CYP3A4, respectively. The value of CYP3A21 was 3% lower than that of cynomolgus monkey CYP3A8. On the other hand, these values were 11 to 23% higher than those of the other experimental animals, including dogs, rabbits, guinea pigs, rats, mice, and hamsters. These results indicate that the marmoset stands at a midpoint between human and nonprimate experimental animals.

摘要

Northern印迹和免疫印迹分析表明,在未经处理的狨猴肝脏中,CYP2B、CYP2C、CYP2D、CYP2E和CYP3A有相当水平的表达。CYP1A也有表达,但程度较低。在未经处理的狨猴小肠中也可检测到CYP3A mRNA;用多氯联苯处理后其含量增加。从肝脏cDNA文库中,分离出两个分别编码CYP2D19和CYP3A21的cDNA克隆(分别为克隆CM2D-1和CM3A-10)。CM2D-1和CM3A-10分别包含编码497和503个氨基酸残基多肽的完整编码区。CYP2D19和CYP3A21推导的氨基酸序列分别与人CYP2D6和CYP3A4有90%的同源性。CYP3A21的值比食蟹猴CYP3A8低3%。另一方面,这些值比包括狗、兔子、豚鼠、大鼠、小鼠和仓鼠在内的其他实验动物高11%至23%。这些结果表明,狨猴处于人类和非灵长类实验动物之间的中间位置。

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