Differences in the developmental expression of rabbit cytochromes P-450 2E1 and 2E2.
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.
Peng
H M
HM
Department of Biological Chemistry, Medical School, University of Michigan, Ann Arbor 48109-0606.
Porter
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Ding
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Coon
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D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015786:Cytochromes b5 / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000201:enzymology / Q000254:growth & development; D008099:Liver / Q000201:enzymology / Q000254:growth & development; D008862:Microsomes, Liver / Q000201:enzymology; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D011247:Pregnancy; D011817:Rabbits
D007527:Isoenzymes; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase