Differential expression of cytochrome P450 enzymes from the CYP2C subfamily in the human brain

Booth Depaz, Iris M., Toselli, Francesca, Wilce, Peter A. and Gillam, Elizabeth M. J. (2015) Differential expression of cytochrome P450 enzymes from the CYP2C subfamily in the human brain. Drug Metabolism and Disposition, 43 3: 353-357. doi:10.1124/dmd.114.061242


Author Booth Depaz, Iris M.
Toselli, Francesca
Wilce, Peter A.
Gillam, Elizabeth M. J.
Title Differential expression of cytochrome P450 enzymes from the CYP2C subfamily in the human brain
Journal name Drug Metabolism and Disposition   Check publisher's open access policy
ISSN 0090-9556
1521-009X
Publication date 2015-03-01
Year available 2015
Sub-type Article (original research)
DOI 10.1124/dmd.114.061242
Open Access Status Not yet assessed
Volume 43
Issue 3
Start page 353
End page 357
Total pages 5
Place of publication Bethesda, MD United States
Publisher American Society for Pharmacology and Experimental Therapy
Language eng
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.
Formatted 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.
Keyword Pharmacology & Pharmacy
Pharmacology & Pharmacy
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 210215
401551
AA12404
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Biomedical Sciences Publications
School of Chemistry and Molecular Biosciences
 
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