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Titolo:
DOPAMINE TRANSPORTER EXPRESSION CONFERS CYTOTOXICITY TO LOW-DOSES OF THE PARKINSONISM-INDUCING NEUROTOXIN 1-METHYL-4-PHENYLPYRIDINIUM
Autore:
PIFL C; GIROS B; CARON MG;
Indirizzi:
UNIV VIENNA,INST BIOCHEM PHARMACOL,BORSCHKEGASSE 8A A-1090 VIENNA AUSTRIA DUKE UNIV,MED CTR,DEPT CELL BIOL,HOWARD HUGHES MED INST LABS DURHAM NC 27710
Titolo Testata:
The Journal of neuroscience
fascicolo: 10, volume: 13, anno: 1993,
pagine: 4246 - 4253
SICI:
0270-6474(1993)13:10<4246:DTECCT>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
BRAIN MONOAMINE-OXIDASE; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; NOREPINEPHRINE UPTAKE; NUCLEUS ACCUMBENS; MOUSE-BRAIN; RAT-BRAIN; NEURONS; CLONING; N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; METABOLITE;
Keywords:
HUMAN DOPAMINE TRANSPORTER; RAT DOPAMINE TRANSPORTER; MPTP (1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE); MPP+ (1-METHYL-4-PHENYLPYRIDINIUM ION); CYTOTOXICITY; DOPAMINE UPTAKE; MPP+ UPTAKE; PARKINSONISM; TRANSFECTION; CELL CULTURE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
54
Recensione:
Indirizzi per estratti:
Citazione:
C. Pifl et al., "DOPAMINE TRANSPORTER EXPRESSION CONFERS CYTOTOXICITY TO LOW-DOSES OF THE PARKINSONISM-INDUCING NEUROTOXIN 1-METHYL-4-PHENYLPYRIDINIUM", The Journal of neuroscience, 13(10), 1993, pp. 4246-4253

Abstract

The uptake of 1-methyl-4-phenylpyridinium (MPP+), the active metabolite of the parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was studied in various mammalian cell lines transfected, respectively, with the cloned human and rat dopamine transporters, and compared with rat striatal synaptosome preparations. Only in neuronally derived cell lines such as NG108-15, NS20Y, and SK-N-MC cells did MPP+ have a K(M) for the cloned transporters comparable tothat of dopamine as seen in rat striatal synaptosomes. In non-neuronally derived cells such as COS-7, CHO, and Ltk cells transiently or permanently expressing the transporters, the K(M) of MPP+ was at least 10-fold higher. The permanent expression of either the cloned human or rat dopamine transporters conferred to SK-N-MC cells susceptibility to the cytotoxic effects of low concentrations of MPP+. The extent of this effect was dependent on the expression level of the dopamine transporters and could be specifically antagonized by the catecholamine uptake inhibitor mazindol. There were no significant differences in the susceptibility to MPP+ of cells expressing similar levels of either the human or rat dopamine transporter. The demonstration for the first timeof a quantitative relationship between the cellular expression of theplasma membrane transporter and the extent of the cytotoxic effects of MPP+ suggests that known differences in vulnerability of various brain regions to MPP+ cytotoxicity might be related to their actual content of dopamine uptake sites. In addition, our results suggest that intrinsic differences in the dopamine transporter proteins of humans and rats are probably not responsible for the marked increased susceptibility of primates to the neurotoxic effects of MPTP, as compared to rats.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 13/07/20 alle ore 09:09:44