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Titolo:
Bilirubin induces apoptosis via activation of NMDA receptors in developingrat brain neurons
Autore:
Grojean, S; Koziel, V; Vert, P; Daval, JL;
Indirizzi:
Univ Henri Poincare, F-54013 Nancy, France Univ Henri Poincare Nancy France F-54013 Poincare, F-54013 Nancy, France
Titolo Testata:
EXPERIMENTAL NEUROLOGY
fascicolo: 2, volume: 166, anno: 2000,
pagine: 334 - 341
SICI:
0014-4886(200012)166:2<334:BIAVAO>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-KINASE-C; PROGRAMMED CELL-DEATH; PRIMARY CORTICAL-NEURONS; METHYL-D-ASPARTATE; ACID-INDUCED DEATH; SEQUENTIAL ACTIVATION; OXIDATIVE STRESS; GLUTAMATE; INHIBITORS; NECROSIS;
Keywords:
bilirubin; cultured neurons; developing rat brain; apoptosis; protein synthesis; caspases; glutamate receptors; protein kinase C;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Grojean, S Univ Henri Poincare, JE 2164,30 Rue Lionnois, F-54013 Nancy, France Univ Henri Poincare JE 2164,30 Rue Lionnois Nancy France F-54013
Citazione:
S. Grojean et al., "Bilirubin induces apoptosis via activation of NMDA receptors in developingrat brain neurons", EXP NEUROL, 166(2), 2000, pp. 334-341

Abstract

Increased amounts of bilirubin, the end product of heme degradation, are known to be detrimental to the central nervous system, especially in pretermnewborns. In an attempt to delineate the cellular mechanisms by which unconjugated bilirubin exerts its toxic effects on neuronal cells in the developing brain, bilirubin (0.25-5 muM) was added to the extracellular medium of6-day-old primary cultured neurons from the embryonic rat forebrain, and cell alterations were studied over the ensuing 96 h. Bilirubin decreased cell viability dose dependently with an ED50 around 1 muM. At the dose of 0.5 muM, it triggered delayed cell death that affected 24% of the neurons. Nuclear incorporation of the fluorescent dye DAPI (4,6-diamidino-2-phenylindole) depicted the presence of apoptosis (16%). Apoptosis features were confirmed by DNA fragmentation reflected by a progressive loss of [H-3]thymidine and sequential changes in macromolecular synthesis, as shown by the time course of [H-3]leucine incorporation, as well as by the beneficial effects of cycloheximide and caspase inhibitors. In parallel, treatments with glutamate receptor antagonists showed that MK-801, but not NBQX, protected neurons against bilirubin neurotoxicity, suggesting a role for NMDA receptors in bilirubin effects. Coupled with previous work about glutamate toxicity in thesame culture model, these data support the hypothesis that low levels of free bilirubin may promote programmed neuronal death corresponding to an apoptotic process which involves caspase activation and requires the participation of NMDA receptors, along with bilirubin-induced inhibition of protein kinase C activity. (C) 2000 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 16:20:27