人脑中CYP2C亚家族细胞色素P450酶的差异表达。
Differential expression of cytochrome P450 enzymes from the CYP2C subfamily in the human brain.
作者信息
Booth Depaz Iris M, Toselli Francesca, Wilce Peter A, Gillam Elizabeth M J
机构信息
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.
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
出版信息
Drug Metab Dispos. 2015 Mar;43(3):353-7. doi: 10.1124/dmd.114.061242. Epub 2014 Dec 11.
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.
细胞色素P450酶家族中的CYP2C亚家族在许多药物的代谢清除过程中发挥着重要作用。CYP2C酶还参与了花生四烯酸代谢生成血管活性环氧二十碳三烯酸的过程。CYP2C8、CYP2C9和CYP2C19在成体肝脏中大量表达；然而，CYP2C酶在脑等肝外组织中的表达情况却鲜为人知。通过对针对独特肽段产生的抗体进行亲和纯化，制备了CYP2C9和CYP2C19的亚型特异性抗体。在所检测的人类大脑的五个区域，即额叶皮质、海马体、基底神经节、杏仁核和小脑中，CYP2C9和CYP2C19均位于微粒体部分。CYP2C9和CYP2C19主要在神经元胞体中被检测到，但在某些区域其表达会延伸至轴突和树突。最后，对酗酒者和年龄匹配的对照组的皮质样本进行比较，结果表明酗酒者的CYP2C9表达增加。
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