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Titolo:
RESCUE OF MESENCEPHALIC DOPAMINE NEURONS BY ANTICANCER DRUG CYTOSINE-ARABINOSIDE
Autore:
MICHEL PP; RUBERG M; AGID Y;
Indirizzi:
HOP LA PITIE SALPETRIERE,INSERM,U289,47 BLVD HOP,BAT PHARM F-75013 PARIS FRANCE
Titolo Testata:
Journal of neurochemistry
fascicolo: 4, volume: 69, anno: 1997,
pagine: 1499 - 1507
SICI:
0022-3042(1997)69:4<1499:ROMDNB>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
DNA-POLYMERASE-ALPHA; CELL-CYCLE; NEUROTROPHIC FACTOR; PROMOTE SURVIVAL; NERVOUS-SYSTEM; PC12 CELLS; IN-VITRO; TOXICITY; DEATH; CULTURE;
Keywords:
ANTIMITOTICS; CYTOSINE ARABINOSIDE; ASTROGLIAL PROLIFERATION; MESENCEPHALIC DOPAMINERGIC NEURONS; NEUROPROTECTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
46
Recensione:
Indirizzi per estratti:
Citazione:
P.P. Michel et al., "RESCUE OF MESENCEPHALIC DOPAMINE NEURONS BY ANTICANCER DRUG CYTOSINE-ARABINOSIDE", Journal of neurochemistry, 69(4), 1997, pp. 1499-1507

Abstract

Nanomolar concentrations of cytosine arabinoside (ara-G), a structural analogue of 2'-deoxycytidine (2'dC) used in the chemotherapy of cancer, proved to be highly effective in preventing the death of postmitotic dopaminergic neurons that occurs spontaneously by apoptosis in mesencephalic cultures. The rescued cells were totally functional and highly differentiated. The trophic/neuroprotective effects of ara-C were (1) specific for dopaminergic neurons; (2) long-lived, remaining detectable several days after withdrawal of the nucleoside analogue from theculture medium; (3) still observed when the treatment was delayed after plating; (4) abolished by an excess of 2'dC or dCTP, or by exposureto the neurotoxin 1-methyl-4-phenylpyridinium; and (5) mimicked by ara-CTP, 5-fluoro-2'-deoxyuridine, and aphidicolin. Autoradiographic studies revealed that ara-C was incorporated exclusively into astrocyte nuclei, suggesting that the dopaminotrophic activity was indirect and resulted from the antiproliferative action of the modified nucleoside on glial cells at concentrations that were not neurotoxic. No evidence was found for putative deleterious or trophic molecules secreted by proliferating or ara-C-treated astrocytes, respectively, suggesting thatneuroglial contact may play a role. Our results suggest a possible mechanism underlying neurodegeneration in Parkinson's disease, where selective loss of dopaminergic neurons in the mesencephalon is accompanied by astrogliosis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/09/20 alle ore 06:33:17