PT  - JOURNAL ARTICLE
AU  - Monica R. Brzezinski
AU  - Helene Boutelet-Bochan
AU  - Richard E. Person
AU  - Alan G. Fantel
AU  - Mont R. Juchau
TI  - Catalytic Activity and Quantitation of Cytochrome P-450 2E1 in Prenatal Human Brain
DP  - 1999 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1648--1653
VI  - 289
IP  - 3
4099  - http://jpet.aspetjournals.org/content/289/3/1648.short
4100  - http://jpet.aspetjournals.org/content/289/3/1648.full
SO  - J Pharmacol Exp Ther1999 Jun 01; 289
AB  - Cytochrome P-450 2E1 (CYP2E1) is a readily inducible hemoprotein that catalyzes the oxidation of endogenous compounds and many low molecular weight xenobiotics. As the major component of the microsomal ethanol oxidizing system, it contributes significantly to ethanol metabolism and the formation of the highly reactive metabolite acetaldehyde. The leaky property of this enzyme results in the generation of reactive oxygen species that can induce oxidative stress and cytotoxic conditions deleterious to development. To further investigate the proposed role of CYP2E1 in the etiology of alcohol teratogenesis, the current study focused on the quantification of CYP2E1 in prenatal human brain, a tissue that is highly vulnerable to the damaging effects of ethanol throughout gestation. In microsomal samples prepared from pools of brain tissues, immunoreactive protein was detected by Western blot analysis using enhanced chemiluminescence, whereas functional protein was estimated with an enzymatic assay usingp-nitrophenol and an electrochemical detection system. CYP2E1 transcript was consistently detected in RNA samples prepared from individual brain tissues using the ribonuclease protection assay. Quantitative data were collected by scanning densitometry and phosphorimaging technology. There was a dramatic increase in human brain CYP2E1 content around gestational day 50 and a fairly constant level was maintained throughout the early fetal period, until at least day 113. The relatively low levels of the P-450 isoform present in conceptal brain may be sufficient to generate reactive intermediates that elicit neuroembryotoxicity following maternal alcohol consumption. The American Society for Pharmacology and Experimental Therapeutics