TAILIEUCHUNG - Báo cáo khoa học: Cytochrome P450 Cyp4x1 is a major P450 protein in mouse brain

A novel cytochrome P450, CYP4x1, was identified in EST databases on the basis of similarity to a conserved region in the C-helix of the CYP4A family. The human and mouse CYP4x1 cDNAs were cloned and found to encode putative cytochrome P450 proteins. Molecular modelling of CYP4x1 predicted an unusual substrate binding channel for the CYP4 fam-ily. | iFEBS Journal Cytochrome P450 Cyp4x1 is a major P450 protein in mouse brain Mohammed Al-Anizy1 Neill J. Horley1 . S. Kuo1 Lorna C. Gillett2 Charles A. Laughton2 David Knndall3 David Ạ Rrrrrntt2 Tem Pni lzni 3 snrl David R Roll1 uav III ixeimaii Uaviu f- . uaiiett leiiy rai nei an u uav Iu n. Dell 1 Schoolof Biology University of Nottingham UK 2 Schoolof Pharmacy University of Nottingham UK 3 Schoolof BiomedicalSciences University of Nottingham UK Keywords Cytochrome P450 peroxisome proliferators brain aorta Correspondence . Bell Schoolof Biology University of Nottingham University Park Nottingham. NG7 2RD UK Fax 44 115 9513251 Tel 44 115 9513210 E-mail Received 16 November 2005 revised 20 December 2005 accepted 23 December 2005 doi A novel cytochrome P450 CYP4x1 was identified in EST databases on the basis of similarity to a conserved region in the C-helix of the CYP4A family. The human and mouse CYP4x1 cDNAs were cloned and found to encode putative cytochrome P450 proteins. Molecular modelling of CYP4x1 predicted an unusual substrate binding channel for the CYP4 family. Expression of human CYP4x1 was detected in brain by EST analysis and in aorta by northern blotting. The mouse cDNA was used to demonstrate that the Cyp4x RNA was expressed principally in brain and at much lower levels in liver hepatic levels of the Cyp4x1 RNA were not affected by treatment with the inducing agents phenobarbital dioxin dexamethasone or ciprofibrate nor were the levels affected in PPARa- - mice. A specific antibody for Cyp4x1 was developed and shown to detect Cyp4x1 in brain quantitation of the Cyp4x1 protein in brain demonstrated w 10 ng of Cyp4x1 protein-mg-1 microsomal protein showing that Cyp4x1 is a major brain P450. Immunohistochemical localization of the Cyp4x1 protein in brain showed specific staining of neurons choroids epithelial cells and vascular endothelial cells. These data suggest an important role for

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