期刊
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 446, 期 2, 页码 101-110出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2005.11.019
关键词
CYP3A; cytochrome P450 3A; P450 3A1; P450 3A2; P450 3A9; P450 3A18; specific antibody; quantitative Western blot; baculovirus expression system; testosterone metabolism; pregnenolone 16 alpha-carbonitrile
资金
- NIEHS NIH HHS [ES05022] Funding Source: Medline
- NIGMS NIH HHS [R01-GM44982] Funding Source: Medline
The purpose of this Study was to identify isozyme-specific antibodies and use them to determine the expression levels of four P450 3A enzymes in the livers of vehicle- and pregnenolone 16 alpha-carbonitrile (PCN)-treated rats of both sexes, since previous work on mRNA levels has shown considerable sexual dimorphism. Using Western blot analysis with four isozyme-specific antibodies, we show that P450 3A1. 3A2, and 3A9 were expressed in vehicle-treated adult female rats at very low levels whereas P450 3A18 was not detected. PCN treatment of females strongly induced the expression of P450 3A1 in the livers with protein product increases of 214-, 3-, and 5-fold for P450 3A1. 3A2. and 3A9, respectively.. and P450 3A 18 was induced to 3.7 pmol/mg protein. In contrast, all four P450 3As were detected in livers of vehicle-treated males, in the order of 3A2 >> 3A 18 > 3A9 congruent to 3A1. The protein product increases induced by PCN treatment of male rats were 92-, 3-. 6-, and 16-fold for P450 3A 1, 3A2, 3A9, and 3A 18, respectively. (c) 2006 Elsevier Inc. All rights reserved.
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