Catalytic activity and quantitation of cytochrome P-450 2E1 in prenatal human brain.

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.

Cytochrome-P450-dependent biotransformation of xenobiotics in human and rodent embryonic tissues.

Profound species differences and developmental stage differences as well as a lack of solid data prevent broad, sweeping generalizations in terms of statements that can be made concerning the prenatal expression of individual P450 isoforms. It is clear, however, that several of such isoforms are expressed at levels that can be toxicologically significant. At present, the greatest interest appears to be in P450s 1A1, 1B1, 2E1, and 3A7, each of which has been reported to be expressed at toxicologically significant levels or at least at potentially toxicologically significant levels during organogenesis.

Expression of CYP2E1 during embryogenesis and fetogenesis in human cephalic tissues: implications for the fetal alcohol syndrome.

Reverse transcription and the polymerase chain reaction (RT-PCR) with oligonucleotide primers designed to target cDNA nucleotides 1241-1357 corresponding to exons 8 (3' end) and 9 (5' end) in human genomic CYP2E1 detected consistently strong signals in 9 of 10 prenatal human brains. Cephalic tissues analyzed were between 54 and 78 days of gestation. RT-PCR signals for expression of CYP2E1 in corresponding human hepatic or adrenal tissues were weaker or, with only 2 exceptions, undetectable.

High affinity binding of pyrethroids to the alpha subunit of brain sodium channels.

Na+ channels are the primary molecular targets of the pyrethroid insecticides. Na+ channels consisting of only a type IIA alpha subunit expressed in Chinese hamster ovary cells responded to pyrethroid treatment in a normal manner: a sustained Na+ current was induced progressively after each depolarizing pulse in a train of stimuli, and this Na+ current decayed slowly on repolarization. These modified Na+ channels could be reactivated at much more negative membrane potentials (V0.