Elsevier

Biochemical Pharmacology

Volume 55, Issue 6, 15 March 1998, Pages 825-830
Biochemical Pharmacology

Research Papers
Regional Distribution of Individual Forms of Cytochrome P450 mRNA in Normal Adult Human Brain

https://doi.org/10.1016/S0006-2952(97)00516-9Get rights and content

Abstract

The cytochromes P450 are a large family of haemoproteins which have a major role in the oxidative metabolism of a wide range of xenobiotics and some endogenous compounds. In this study the presence of individual members of the CYP1, CYP2 and CYP3 P450 families has been investigated by reverse transcriptase polymerase chain reaction in different regions of normal human brain consisting of frontal and temporal cortices, mid brain, cerebellum, pons and medulla. All the P450s were identified in specific regions of brain with CYP1A1 and CYP2C being the most frequently expressed forms of P450. Sequencing identified the CYP2C PCR product as CYP2C8. This study indicates that individual P450 mRNAs are present in human brain and are found in specific brain regions. The distribution of individual P450s in different regions of human brain is likely to be highly important in determining the response of the brain to toxic foreign compounds.

Section snippets

Tissue

Normal human brain was obtained, with permission, from autopsies carried out in the Department of Pathology, University of Aberdeen. The clinical details and causes of death are summarised in Table 1. None of the patients displayed any sign of neurological disease and they were non-smokers who had not been treated with any drugs known to induce P450 expression. All the brains appeared normal at post-mortem examination and tissue samples were obtained within 24 hr of death from the following

Results

All the samples of brain showed the presence of β-actin mRNA (Fig. 1) and thus were subjected to PCR for individual P450s. The presence and distribution of individual P450s in the specific regions of the five different brains was similar. CYP1A1 mRNA was detected in cerebellum, mid brain, basal ganglia, frontal cortex and temporal cortex but was not detected in either the medulla or pons while CYP1A2 mRNA was detected only weakly in the basal ganglia and not in any of the other regions of

Discussion

The P450s have a critical role in the activation and deactivation of many toxic foreign chemicals and the relative expression of specific forms of cytochrome P450 in a particular tissue is important in determining the toxicity of an individual chemical [12]. It is therefore important to determine the expression of different forms of P450 in specific areas of the brain to further understand the effect of toxic substances in brain. In rodent brain multiple forms of P450 have been shown to be

Acknowledgements

We thank The Association for International Cancer Research and Tenovus-Scotland for financial support.

References (31)

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