Induction of CYP1A1, but not CYP1A2, in adrenals of 3, 3'-methylcholanthrene-treated guinea pigs.
Induction of CYP1A1, but not CYP1A2, in adrenals of 3, 3'-methylcholanthrene-treated guinea pigs.
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在 3, 3-甲基胆蒽处理的豚鼠的肾上腺中诱导 CYP1A1，但不诱导 CYP1A2。
DOI：
10.1006/abbi.1998.0636
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Shaw,PM
中科院分区：
文献类型：
--
作者：
Black,VH;Wang,AF;Henry,M;Shaw,PM
为探讨CYP 1A同系物在豚鼠肾上腺中的诱导作用，比较了CYP 1A原型诱导剂3，3 ′-甲基胆蒽在豚鼠肾上腺和肝脏中的作用。Western blot分析显示，3，3 ′-甲基胆蒽处理的豚鼠肝微粒体中CYP 1A 1（53 kDa）和CYP 1A 2（56 kDa）的水平均升高。在肾上腺中，仅在3，3 ′-甲基胆蒽处理后检测到与肝CYP 1A 1共迁移的免疫反应蛋白。在肾上腺微粒体中从未检测到与CYP 1A 2共迁移的蛋白质。3，3 ′-甲基胆蒽处理后，在肝脏中观察到第三种诱导免疫反应蛋白（57 kDa），但在肾上腺中未观察到。另一种免疫反应性蛋白（52 kDa），组成性存在于肝脏和肾上腺微粒体中，在这两种组织中均未被3，3 ′-甲基胆蒽诱导。可诱导的57-kDa和不可诱导的52-kDa蛋白的精确身份仍有待确定。然而，通过RT-PCR、北方印迹和序列分析证实了肾上腺中53-kDa蛋白与CYP 1A 1的同一性。类似的分析表明，尽管在肾上腺微粒体中未检测到56-kDa蛋白，但在对照动物的肾上腺中存在CYP 1A 2 mRNA。值得注意的是，3，3 ′-甲基胆蒽处理后，肾上腺中的CYP 1A 2 mRNA降低，但肝脏中的mRNA升高，强调了两种组织中CYP 1A表达调节的差异。乙氧基试卤灵和甲氧基试卤灵代谢水平分别与CYP 1A 1和CYP 1A 2蛋白水平相关。
To test the inducibility of CYP1A homologs in guinea pig adrenal, the effects of 3,3′-methylcholanthrene, an archetypal inducer of CYP1A, were compared in guinea pig adrenal and liver. Western blot analysis showed that levels of both CYP1A1 (53 kDa) and CYP1A2 (56 kDa) increasedin liver microsomes of 3,3′-methylcholanthrene-treated guinea pigs. In adrenals, an immunoreactive protein comigrating with liver CYP1A1 was detected only after 3,3′-methylcholanthrene treatment. Protein comigrating with CYP1A2 was never detected in adrenal microsomes. A third inducible immunoreactive protein (57 kDa) was seen in liver, but not adrenal, after 3,3′-methylcholanthrene treatment. Another immunoreactive protein (52 kDa), present constitutively in liver and adrenal microsomes, was not induced in either tissue by 3,3′-methylcholanthrene. The precise identities of the inducible 57-kDa and the noninducible 52-kDa proteins remain to be determined. However, the identity of the 53-kDa protein in the adrenal as CYP1A1 was confirmed by RT-PCR, Northern blot, and sequence analysis. Similar analyses demonstrated that, despite the fact that the 56-kDa protein was not detectable in adrenal microsomes, CYP1A2 mRNA was present in adrenals of control animals. Strikingly, CYP1A2 mRNA decreased in adrenal, but increased in liver, following 3,3′-methylcholanthrene treatment, underscoring differences in the regulation of CYP1A expression in the two tissues. Levels of ethoxyresorufin and methyoxyresorufin metabolism correlated with levels of CYP1A1 and CYP1A2 protein, respectively.