Document Detail


Overexpression of CYP2D6 attenuates the toxicity of MPP+ in actively dividing and differentiated PC12 cells.
MedLine Citation:
PMID:  14686785     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Clonal pheochromocytoma cell lines overexpressing cytochrome P450 2D6 (CYP2D6) were established. CYP2D6 was localized in the endoplasmic reticulum, and its enzymatic activity in the microsomal fraction was confirmed by using high performance liquid chromatography analysis with [guanidine-14C]debrisoquine as a substrate. Overexpression of CYP2D6 protected both actively dividing and differentiated cells against the toxic effects of 1-methyl-4-phenylpyridinium ion at the concentration range of 20-40 microM, as assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The production of reactive oxygen species in the mitochondria was suppressed. The cytotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine was unchanged in both actively dividing and differentiated cells overexpressing CYP2D6 versus mock-transfected controls at concentrations up to 500 microM. These results suggest that the lowered enzyme activity of CYP2D6 in individuals termed "poor metabolizers" may represent a risk factor from exposure to select neurotoxicants.
Authors:
Naomi Matoh; Seigo Tanaka; Masanori Takehashi; Marek Banasik; Todd Stedeford; Eliezer Masliah; Shigehiko Suzuki; Yoshihiko Nishimura; Kunihiro Ueda
Related Documents :
7894495 - Higher plant metabolism of xenobiotics: the 'green liver' concept.
20359285 - Comparison of enzyme kinetic parameters obtained in vitro for reactions mediated by hum...
11124225 - A method for the simultaneous evaluation of the activities of seven major human drug-me...
1857335 - Enantiomer/enantiomer interaction of (s)- and (r)-propafenone for cytochrome p450iid6-c...
3917915 - 4-aminobutyrate:2-oxoglutarate aminotransferase of streptomyces griseus: purification a...
1856785 - An assessment of 2,4 tda formation from surgitek polyurethane foam under simulated phys...
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Gene expression     Volume:  11     ISSN:  1052-2166     ISO Abbreviation:  Gene Expr.     Publication Date:  2003  
Date Detail:
Created Date:  2003-12-22     Completed Date:  2004-02-02     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9200651     Medline TA:  Gene Expr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  117-24     Citation Subset:  IM    
Affiliation:
Laboratory of Molecular Clinical Chemistry, Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
1-Methyl-4-phenylpyridinium / toxicity*
Animals
Cell Differentiation / drug effects
Cell Division / drug effects
Cytochrome P-450 CYP2D6 / genetics*,  metabolism
Gene Expression Regulation, Enzymologic / physiology*
Herbicides / toxicity*
Humans
Mitochondria / metabolism
PC12 Cells / cytology,  enzymology
Rats
Reactive Oxygen Species / metabolism
Grant Support
ID/Acronym/Agency:
AG5131/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Herbicides; 0/Reactive Oxygen Species; 28289-54-5/1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 48134-75-4/1-Methyl-4-phenylpyridinium; EC 1.14.14.1/Cytochrome P-450 CYP2D6

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Simultaneous monitoring of organic acids and sugars in fresh and processed apple juice by Fourier tr...
Next Document:  Transcriptomic classification of antitumor agents: application to the analysis of the antitumoral ef...