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Titolo:
N-methyl-D-aspartate receptor-mediated mitochondrial Ca2+ overload in acute excitotoxic motor neuron death: A mechanism distinct from chronic neurotoxicity after Ca2+ influx
Autore:
Urushitani, M; Nakamizo, T; Inoue, R; Sawada, H; Kihara, T; Honda, K; Akaike, A; Shimohama, S;
Indirizzi:
Kyoto Univ, Grad Sch Med, Dept Neurol, Sakyo Ku, Kyoto 6068507, Japan Kyoto Univ Kyoto Japan 6068507 pt Neurol, Sakyo Ku, Kyoto 6068507, Japan Kyoto Univ, Grad Sch Pharmaceut Sci, Dept Pharmacol, Sakyo Ku, Kyoto, Japan Kyoto Univ Kyoto Japan ceut Sci, Dept Pharmacol, Sakyo Ku, Kyoto, Japan
Titolo Testata:
JOURNAL OF NEUROSCIENCE RESEARCH
fascicolo: 5, volume: 63, anno: 2001,
pagine: 377 - 387
SICI:
0360-4012(20010301)63:5<377:NRMCOI>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
CEREBELLAR GRANULE CELLS; AMYOTROPHIC-LATERAL-SCLEROSIS; ACUTE GLUTAMATE EXCITOTOXICITY; CULTURED FOREBRAIN NEURONS; SPINAL-CORD; IN-VITRO; INDUCED APOPTOSIS; SUPEROXIDE PRODUCTION; HIPPOCAMPAL-NEURONS; ACID RECEPTORS;
Keywords:
glutamate; calcium; reactive oxygen species; mitochondria; motor neuron; spinal cord;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
51
Recensione:
Indirizzi per estratti:
Indirizzo: Shimohama, S Kyoto Univ, Grad Sch Med, Dept Neurol, Sakyo Ku, 54 Shogoin Kawaharacho, Kyoto 6068507, Japan Kyoto Univ 54 Shogoin Kawaharacho Kyoto Japan 6068507 Japan
Citazione:
M. Urushitani et al., "N-methyl-D-aspartate receptor-mediated mitochondrial Ca2+ overload in acute excitotoxic motor neuron death: A mechanism distinct from chronic neurotoxicity after Ca2+ influx", J NEUROSC R, 63(5), 2001, pp. 377-387

Abstract

Mitochondrial uptake of Ca2+ has recently been found to play an important role in glutamate-induced neurotoxicity (GNT) as well as in the activation of Ca2+-dependent molecules, such as calmodulin and neuronal nitric oxide synthase (nNOS), in the cytoplasm, Prolonged exposure to glutamate injures motor neurons predominantly through the activation of Ca2+/calmodulin-nNOS, as previously reported, and is, in part, associated with the pathogenesis of amyotrophic lateral sclerosis (ALS), In the present study, we investigated how mitochondrial uptake of Ca2+ is involved in GNT in spinal motor neurons. Acute excitotoxicity induced by exposure to 0.5 mM glutamate for 5 min was found in both motor and nonmotor neurons in cultured spinal cords from rat embryos and was dependent on extracellular Ca2+ and on N-methyl-D-aspartate (NWDA) receptor activation. Mitochondrial uncouplers markedly blocked acute excitotoxicity, and membrane-permeable superoxide dismutase mimics attenuated acute excitotoxicity induced by glutamate and NMDA but not by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) or kainate, Fluorimetric analysis showed that mitochondrial Ca2+ was elevated promptly with subsequent accumulation of reactive oxygen species (ROS) in the mitochondria. An NMDA receptor antagonist and a mitochondrial uncoupler eliminated the increase in fluorescence of mitochondrial Ca2+ and ROS indicators. These data indicate that acute excitotoxicity in spinal neurons is mediated by mitochondrial Ca2+ overload and ROS generation through the activation of NMDA receptors. This mechanism is different from that of chronic GNT. (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/04/20 alle ore 11:10:14