Stapleton, G. , Steel, M., Richardson, M., Mason, J. O., Rose, K. A., Morris, R. G. M. and Lathe, R. (1995) A novel cytochrome P450 expressed primarily in brain. Journal of Biological Chemistry, 270(50), pp. 29739-29745. (doi: 10.1074/jbc.270.50.29739) (PMID:8530364)
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Publisher's URL: http://www.jbc.org/content/270/50/29739
Abstract
hct-1 (hippocampal transcript) was detected in a differential screen of a rat hippocampal cDNA library. Expression of hct-1 was enriched in the formation but was also detected in rat liver and kidney, though at much lower levels; expression was barely detectable in testis, ovary, and adrenal. In liver, unlike brain, expression was sexually dimorphic; hepatic expression was greatly reduced in female rats. In mouse, brain expression was widespread, with the highest levels being detected in corpus callosum; only low levels were detected in liver. Sequence analysis of rat and mouse hct-1 cDNAs revealed extensive homologies with cytochrome P450s (CYPs), a diverse family of heme-binding monooxygenases that metabolize a range of substrates including steroids, fatty acids, and xenobiotics. Among the CYPs, hct-1 is most similar (39% at the amino acid sequence) to cholesterol 7α-hydroxylase (CYP7) and contains a postulated steroidogenic domain present in other steroid-metabolizing CYPs but clearly represents a type of CYP not previously reported. Genomic Southern analysis suggests that a single gene corresponding to hct-1 is present in mouse, rat, and human. hct-1 is unusual in that, unlike all other CYPs described, the primary site of expression is in the brain. Similarity to CYP7 and other steroid-metabolizing CYPs may argue that hct-1 (CYP7B) plays a role in steroid metabolism in brain, notable because of the documented ability of brain-derived steroids (neurosteroids) to modulate cognitive function in vivo.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Stapleton, Dr Genevieve |
Authors: | Stapleton, G., Steel, M., Richardson, M., Mason, J. O., Rose, K. A., Morris, R. G. M., and Lathe, R. |
College/School: | College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing |
Journal Name: | Journal of Biological Chemistry |
Publisher: | American Society for Biochemistry and Molecular Biology, Inc. |
ISSN: | 0021-9258 |
ISSN (Online): | 1083-351X |
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