Cytochrome p450 mRNA expression in the rodent brain: species-, sex-, and region-dependent differences

Marianna Stamou; Xianai Wu; Izabela Kania-Korwel; Hans-Joachim Lehmler; Pamela J Lein

doi:10.1124/dmd.113.054239

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Cytochrome p450 mRNA expression in the rodent brain: species-, sex-, and region-dependent differences

Journal article

Open access

Peer reviewed

Cytochrome p450 mRNA expression in the rodent brain: species-, sex-, and region-dependent differences

Marianna Stamou, Xianai Wu, Izabela Kania-Korwel, Hans-Joachim Lehmler and Pamela J Lein

Drug metabolism and disposition, Vol.42(2), pp.239-244

02/2014

DOI: 10.1124/dmd.113.054239

PMCID: PMC3912540

PMID: 24255117

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Abstract

Cytochrome P450 (P450) enzymes play a critical role in the activation and detoxication of many neurotoxic chemicals. Although research has largely focused on P450-mediated metabolism in the liver, emerging evidence suggests that brain P450s influence neurotoxicity by modulating local metabolite levels. As a first step toward better understanding the relative role of brain P450s in determining neurotoxic outcome, we characterized mRNA expression of specific P450 isoforms in the rodent brain. Adult mice (male and female) and rats (male) were treated with vehicle, phenobarbital, or dexamethasone. Transcripts for CYP2B, CYP3A, CYP1A2, and the orphan CYP4X1 and CYP2S1 were quantified in the liver, hippocampus, cortex, and cerebellum by quantitative (real-time) polymerase chain reaction. These P450s were all detected in the liver with the exception of CYP4X1, which was detected in rat but not mouse liver. P450 expression profiles in the brain varied regionally. With the exception of the hippocampus, there were no sex differences in regional brain P450 expression profiles in mice; however, there were marked species differences. In the liver, phenobarbital induced CYP2B expression in both species. Dexamethasone induced hepatic CYP2B and CYP3A in mice but not rats. In contrast, brain P450s did not respond to these classic hepatic P450 inducers. Our findings demonstrate that P450 mRNA expression in the brain varies by region, regional brain P450 profiles vary between species, and their induction varies from that of hepatic P450s. These novel data will be useful for designing mechanistic studies to examine the relative role of P450-mediated brain metabolism in neurotoxicity.

Liver - enzymology

Species Specificity

Isoenzymes

Mice, Inbred C57BL

Brain - enzymology

Enzyme Induction

Rats

Male

Rats, Sprague-Dawley

Brain - drug effects

RNA, Messenger - biosynthesis

Animals

Liver - drug effects

Sex Factors

Cytochrome P-450 Enzyme System - biosynthesis

Cytochrome P-450 Enzyme System - genetics

Female

Mice

Synthesis Core

Details

Title: Subtitle: Cytochrome p450 mRNA expression in the rodent brain: species-, sex-, and region-dependent differences
Creators: Marianna Stamou - Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California (M.S., P.J.L.) and Department of Occupational and Environmental Health, College of Public Health, The University of Iowa, Iowa City, Iowa (X.W., I.K.-K., H.-J.L.)
Xianai Wu
Izabela Kania-Korwel
Hans-Joachim Lehmler
Pamela J Lein
Resource Type: Journal article
Publication Details: Drug metabolism and disposition, Vol.42(2), pp.239-244
DOI: 10.1124/dmd.113.054239
PMID: 24255117
PMCID: PMC3912540
NLM abbreviation: Drug Metab Dispos
ISSN: 0090-9556
eISSN: 1521-009X
Publisher: United States
Grant note: P30 ES005605 / NIEHS NIH HHS P42 ES004699 / NIEHS NIH HHS R01 ES017425 / NIEHS NIH HHS P42 ES04699 / NIEHS NIH HHS
Language: English
Date published: 02/2014
Academic Unit: Occupational and Environmental Health; Iowa Neuroscience Institute; Iowa Superfund Research Program
Record Identifier: 9984001084002771

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