Predominantly neuronal expression of cytochrome P450 isoforms CYP3A11 and CYP3A13 in mouse brain.
Despite the very small amounts of cytochrome P450 enzymes expressed in different areas and cell populations of the brain as compared with the liver, there is significant evidence for their specific involvement in brain development, function, and plasticity. Nevertheless, the current discussion about occurrence and importance of cerebral cytochrome P450 isoforms is determined by controversial interpretations of their function in general and with respect to single isoforms. Continuing a series of publications about brain P450 isoforms, we now present evidence for the expression of cytochrome P450 3A11 and 3A13 in mouse brain. Immunocytochemical and non-radioactive in situ hybridization studies revealed identical distribution of their proteins and mRNAs throughout the brain especially in neuronal populations, and to some extent in astrocytes. The cerebral expression of these P450 isoforms was confirmed by Western blot and RNAse protection assay analysis. The well-known testosterone-metabolizing capacity and the inducibility of cytochrome P450 3a isoforms by xenobiotics as well as their presence in steroid hormone-sensitive areas and neurons (e.g. hippocampus) clarify the significance of these isoforms for impairment of steroid hormone actions by P450-inducing environmental substances. Therefore, investigation of inducible cerebral P450 isoforms which are able to metabolize xenobiotics as well as steroid hormones might help us to understand neuroendocrine regulation of brain's plasticity.
Hagemeyer
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CE
Department of Neuropathology, University of Freiburg, Neurocenter, Breisacher Strasse 64, 79106 Freiburg, Germany. hagemeyer@hotmail.com
Rosenbrock
H
H
Ditter
M
M
Knoth
R
R
Volk
B
B
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D010672:Phenytoin / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis
D000927:Anticonvulsants; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D010672:Phenytoin; D001189:Aryl Hydrocarbon Hydroxylases; C496508:Cyp3a11 protein, mouse; C496509:Cyp3a13 protein, mouse; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating