Cytochrome P450 Cyp4x1 is a major P450 protein in mouse brain

被引:31
作者
Al-Anizy, M
Horley, NJ
Kuo, CWS
Gillett, LC
Laughton, CA
Kendall, D
Barrett, DA
Parker, T
Bell, DR
机构
[1] Univ Nottingham, Sch Biol, Nottingham NG7 2RD, England
[2] Univ Nottingham, Sch Pharm, Nottingham NG7 2RD, England
[3] Univ Nottingham, Sch Biomed Sci, Nottingham NG7 2RD, England
基金
英国惠康基金;
关键词
cytochrome P450; peroxisome proliferators; brain; aorta;
D O I
10.1111/j.1742-4658.2006.05119.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 PPAR alpha-/- mice. A specific antibody for Cyp4x1 was developed, and shown to detect Cyp4x1 in brain; quantitation of the Cyp4x1 protein in brain demonstrated approximate to 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 Cyp4x1 in the brain.
引用
收藏
页码:936 / 947
页数:12
相关论文
共 46 条
  • [1] Peroxisome proliferator-activated receptor-α regulates lipid homeostasis, but is not associated with obesity -: Studies with congenic mouse lines
    Akiyama, TE
    Nicol, CJ
    Fievet, C
    Staels, B
    Ward, JM
    Auwerx, J
    Lee, SST
    Gonzalez, FJ
    Peters, JM
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (42) : 39088 - 39093
  • [2] Omega-oxidation of monocarboxylic acids in rat brain
    Alexander, JJ
    Snyder, A
    Tonsgard, JH
    [J]. NEUROCHEMICAL RESEARCH, 1998, 23 (02) : 227 - 233
  • [3] MECHANISTICALLY-BASED HUMAN HAZARD ASSESSMENT OF PEROXISOME PROLIFERATOR-INDUCED HEPATOCARCINOGENESIS
    ASHBY, J
    BRADY, A
    ELCOMBE, CR
    ELLIOTT, BM
    ISHMAEL, J
    ODUM, J
    TUGWOOD, JD
    KETTLE, S
    PURCHASE, IFH
    [J]. HUMAN & EXPERIMENTAL TOXICOLOGY, 1994, 13 : S1 - S117
  • [4] Molecular basis of non-responsiveness to peroxisome proliferators:: the guinea-pig PPARα is functional and mediates peroxisome proliferator-induced hypolipidaemia
    Bell, AR
    Savory, R
    Horley, NJ
    Choudhury, AI
    Dickins, M
    Gray, TJB
    Salter, AM
    Bell, DR
    [J]. BIOCHEMICAL JOURNAL, 1998, 332 : 689 - 693
  • [5] REGULATION OF DIFFERENTIALLY SPLICED TRANSCRIPTS OF ACYL-COA OXIDASE IN THE RAT
    BELL, DR
    ELCOMBE, CR
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1090 (02) : 211 - 215
  • [6] SPECIES-SPECIFIC INDUCTION OF CYTOCHROME-P-450 4A-RNAS - PCR CLONING OF PARTIAL GUINEA-PIG, HUMAN AND MOUSE CYP4A-CDNAS
    BELL, DR
    PLANT, NJ
    RIDER, CG
    NA, L
    BROWN, S
    ATEITALLA, I
    ACHARYA, SK
    DAVIES, MH
    ELIAS, E
    JENKINS, NA
    GILBERT, DJ
    COPELAND, NG
    ELCOMBE, CR
    [J]. BIOCHEMICAL JOURNAL, 1993, 294 : 173 - 180
  • [7] BHAGWAT SV, 1995, DRUG METAB DISPOS, V23, P651
  • [8] MICROSOMAL CYTOCHROME P450-MEDIATED LIVER AND BRAIN ANANDAMIDE METABOLISM
    BORNHEIM, LM
    KIM, KY
    CHEN, BL
    CORREIA, MA
    [J]. BIOCHEMICAL PHARMACOLOGY, 1995, 50 (05) : 677 - 686
  • [9] Prediction of protein side-chain rotamers from a backbone-dependent rotamer library: A new homology modeling tool
    Bower, MJ
    Cohen, FE
    Dunbrack, RL
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1997, 267 (05) : 1268 - 1282
  • [10] Identification of a novel cytochrome P450, CYP4X1, with unique localization specific to the brain
    Bylund, J
    Zhang, CY
    Harder, DR
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2002, 296 (03) : 677 - 684