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

被引:32
作者
Igarashi, T
Sakuma, T
Isogai, M
Nagata, R
Kamataki, T
机构
[1] HOKKAIDO UNIV,FAC PHARMACEUT SCI,DIV DRUG METAB,KITA KU,SAPPORO,HOKKAIDO 060,JAPAN
[2] DAIICHI PURE CHEM CO LTD,TOKAI,IBARAKI 31911,JAPAN
[3] SHIN NIPPON BIOCHEM LABS LTD,YOSHIA,KAGOSHIMA 89113,JAPAN
关键词
marmoset; P450; CYP; induction; liver; small intestine; lung; kidney;
D O I
10.1006/abbi.1996.9852
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 1997 Academic Press.
引用
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页码:85 / 91
页数:7
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