A novel female-specific member of the CYP3A gene subfamily in the mouse liver
A novel female-specific member of the CYP3A gene subfamily in the mouse liver
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DOI：
10.1006/abbi.2000.1747
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发表时间：
2000-05-01
影响因子：
3.9
通讯作者：
Nemoto, N
中科院分区：
文献类型：
--
作者：
Sakuma, T;Takai, M;Nemoto, N
免疫印迹法观察成年小鼠肝脏中雌性特异性CYP3A的表达。为了表征这种细胞色素P450，我们确定了其cDNA的初级结构并检测了其表达谱。该细胞色素P450由504个氨基酸组成，与小鼠CYP3A11、3A13、3A16和3A25分别具有92、68、88和69%的氨基酸序列同源性，被命名为CYP3A41，为小鼠CYP3A新基因。在雌性肝脏中，CYP3A41 mRNA的表达水平与成年小鼠肝脏中主要的CYP3A11酶的表达水平相当。在雌雄动物出生后立即在肝脏中检测到CYP3A41 mRNA的表达，但在雌性动物中随着年龄的增长而增加，而在雄性动物中逐渐减少，导致肝脏中以雌性特异性表达为主。在雌性小鼠的肾脏中检测到少量的CYP3A41 mRNA，在雌性小鼠的胃、卵巢和心脏以及雄性小鼠的睾丸中检测到微量的CYP3A41 mRNA。性腺切除术和性激素治疗表明雌二醇和睾酮能够分别诱导和抑制肝脏中CYP3A41 mRNA的表达。在经典CYP3A诱导剂中，地塞米松、利福平和3-甲基胆蒽对两性肝脏中CYP3A41 mRNA水平均无影响。另一方面，孕烯醇酮- 16 α -碳腈和苯巴比妥抑制CYP3A41水平至未治疗雌鼠的一半。这些观察结果表明，CYP3A41是雌性特异性CYP3A，是雌性小鼠肝脏中主要的CYP3A形式之一。(C) 2000年学术出版社。
Expression of a female-specific CYP3A in the adult mouse liver was observed on immunoblotting analysis. To characterize this cytochrome P450, we determined the primary structure of its cDNA and examined its expression profile. This cytochrome P450 consisted of 504 amino acids and showed 92, 68, 88, and 69% amino acid sequence identity with mouse CYP3A11, 3A13, 3A16, and 3A25, respectively, and was designated as CYP3A41, a new mouse CYP3A gene. In the female liver, levels of CYP3A41 mRNA expression were comparable to those of CYP3A11, the major CYP3A enzyme in the adult mouse liver. Expression of CYP3A41 mRNA was detected immediately after birth in the livers of animals of both sexes, but increased with age in females, whereas it was gradually reduced in males, resulting in predominantly female-specific expression in livers. Lesser amounts of CYP3A41 mRNA were detected in the kidneys of female mice, with traces in the stomach, ovary, and heart of female mice and in the testis of male mice. Gonadectomy and sex hormone treatment indicated that estradiol and testosterone were able to induce and suppress the expression of CYP3A41 mRNA in the liver, respectively. Among the classical CYP3A inducers, dexamethasone, rifampicin, and 3-methylcholanthrene did not affect the level of CYP3A41 mRNA in the liver of either sex. On the other hand, pregnenolone 16 alpha-carbonitrile and phenobarbital suppressed CYP3A41 level to half that of untreated female mice. These observations indicated that CYP3A41 is a female-specific CYP3A and one of the major CYP3A forms in the female mouse liver. (C) 2000 Academic Press.