Peng H M, Porter T D, Ding X X, Coon M J
Department of Biological Chemistry, Medical School, University of Michigan, Ann Arbor 48109-0606.
Mol Pharmacol. 1991 Jul;40(1):58-62.
The alcohol-inducible CYP2E subfamily in rabbits contains two genes; CYP2E1 encodes the cytochrome earlier termed P-450 3a, and CYP2E2 encodes a cytochrome that is 97% identical in amino acid sequence to cytochrome P-450 (P-450) 2E1. In the present studies, the ontogenic expression of these two cytochromes was examined. In liver, P-450 2E2 mRNA is detectable immediately after birth and reaches slightly greater than the adult level at 2 weeks of age; in contrast, P-450 2E1 mRNA is not detectable until day 14 and increases rapidly to approximately twice the adult level at 5 weeks of age. P-450 2E protein is present in liver immediately after birth, coincident with the appearance of P-450 2E2 mRNA, peaks at 2 weeks, and then, despite the continued elevation in P-450 2E mRNA, decreases to the adult level at 5 weeks. In kidney, P-450 2E2 mRNA is not detectable at any age; P-450 2E1 mRNA, however, is present at 1 week, and the level increases to about half the adult level at 5 weeks of age. P-450 2E protein in this tissue is elevated at 2 weeks, relative to mRNA levels, and reaches approximately half the adult level at 5 weeks. The lack of close correlation between mRNA and protein levels in the liver and kidney of newborn rabbits indicates that the posttranscriptional control of P-450 2E enzyme levels that predominates in adult animals is also operative during the neonatal period. Monooxygenase activities with ethanol and p-nitrophenol as substrates reflect the developmental increase in P-450 2E protein, as well as the appearance and levels of spectrally detectable P-450, cytochrome b5, and NADPH-P-450 reductase in hepatic microsomes. The expression of P-450 2E2, but not P-450 2E1, in early neonates suggests that these two closely related cytochromes may have functional differences that are important during the first few weeks of life.
兔子体内酒精诱导型CYP2E亚家族包含两个基因；CYP2E1编码的细胞色素之前被称为P-450 3a，而CYP2E2编码的细胞色素氨基酸序列与细胞色素P-450（P-450）2E1有97%的同源性。在本研究中，对这两种细胞色素的个体发生表达进行了检测。在肝脏中，出生后即可检测到P-450 2E2 mRNA，在2周龄时略高于成年水平；相比之下，P-450 2E1 mRNA直到第14天才可检测到，并在5周龄时迅速增加至成年水平的约两倍。P-450 2E蛋白在出生后立即出现在肝脏中，与P-450 2E2 mRNA的出现同步，在2周时达到峰值，然后，尽管P-450 2E mRNA持续升高，但在5周时降至成年水平。在肾脏中，任何年龄都检测不到P-450 2E2 mRNA；然而，P-450 2E1 mRNA在1周时存在，其水平在5周龄时增加到成年水平的约一半。该组织中的P-450 2E蛋白在2周时相对于mRNA水平升高，并在5周时达到成年水平的约一半。新生兔子肝脏和肾脏中mRNA水平与蛋白水平缺乏密切相关性，这表明在成年动物中占主导地位的P-450 2E酶水平的转录后调控在新生儿期也起作用。以乙醇和对硝基苯酚为底物的单加氧酶活性反映了P-450 2E蛋白的发育性增加，以及肝微粒体中光谱可检测的P-450、细胞色素b5和NADPH-P-450还原酶的出现和水平。早期新生儿中P-450 2E2而非P-450 2E1的表达表明，这两种密切相关的细胞色素可能具有在生命最初几周很重要的功能差异。
