title: Differential expression of cytochrome P450 enzymes from the CYP2C subfamily in the human brain.
abstract: Cytochrome P450 enzymes from the CYP2C subfamily play a prominent role in the metabolic clearance of many drugs. CYP2C enzymes have also been implicated in the metabolism of arachidonic acid to vasoactive epoxyeicosatrienoic acids. CYP2C8, CYP2C9, and CYP2C19 are expressed in the adult liver at significant levels; however, the expression of CYP2C enzymes in extrahepatic tissues such as the brain is less well characterized. Form-specific antibodies to CYP2C9 and CYP2C19 were prepared by affinity purification of antibodies raised to unique peptides. CYP2C9 and CYP2C19 were located in microsomal fractions of all five human brain regions examined, namely the frontal cortex, hippocampus, basal ganglia, amygdala, and cerebellum. Both CYP2C9 and CYP2C19 were detected predominantly within the neuronal soma but with expression extending down axons and dendrites in certain regions. Finally, a comparison of cortex samples from alcoholics and age-matched controls suggested that CYP2C9 expression was increased in alcoholics.
authors.affiliation: Schools of Biomedical Sciences (I.M.B.D.) and Chemistry and Molecular Biosciences (F.T., P.A.W., E.M.J.G.), University of Queensland, Brisbane, Australia.
authors.forename: Iris M
authors.initials: IM
authors.lastname: Booth Depaz
authors.affiliation: Schools of Biomedical Sciences (I.M.B.D.) and Chemistry and Molecular Biosciences (F.T., P.A.W., E.M.J.G.), University of Queensland, Brisbane, Australia.
authors.forename: Francesca
authors.initials: F
authors.lastname: Toselli
authors.affiliation: Schools of Biomedical Sciences (I.M.B.D.) and Chemistry and Molecular Biosciences (F.T., P.A.W., E.M.J.G.), University of Queensland, Brisbane, Australia.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Wilce
authors.affiliation: Schools of Biomedical Sciences (I.M.B.D.) and Chemistry and Molecular Biosciences (F.T., P.A.W., E.M.J.G.), University of Queensland, Brisbane, Australia e.gillam@uq.edu.au.
authors.forename: Elizabeth M J
authors.initials: EM
authors.lastname: Gillam
mesh_terms: D000328:Adult; D057229:Alcoholics; D000595:Amino Acid Sequence; D016718:Arachidonic Acid / Q000378:metabolism; D001921:Brain / Q000201:enzymology* / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data
chemical_list: C400322:cytochrome P-450 CYP2C subfamily; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System