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Titolo:
Enzymatic degradation protects neurons from glutamate excitotoxicity
Autore:
Matthews, CC; Zielke, HR; Wollack, JB; Fishman, PS;
Indirizzi:
Univ Maryland, Dept Neurol, Sch Med, Baltimore, MD 21201 USA Univ Maryland Baltimore MD USA 21201 ol, Sch Med, Baltimore, MD 21201 USA Univ Maryland, Dept Pediat, Sch Med, Baltimore, MD 21201 USA Univ Maryland Baltimore MD USA 21201 at, Sch Med, Baltimore, MD 21201 USA Baltimore Vet Affairs Med Ctr, Res Serv, Baltimore, MD USA Baltimore Vet Affairs Med Ctr Baltimore MD USA s Serv, Baltimore, MD USA
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 3, volume: 75, anno: 2000,
pagine: 1045 - 1052
SICI:
0022-3042(200009)75:3<1045:EDPNFG>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
SYNAPTICALLY RELEASED GLUTAMATE; AMYOTROPHIC-LATERAL-SCLEROSIS; LINKED ACIDIC DIPEPTIDASE; RAT CORTICAL CULTURES; INHIBITOR L-TRANS-PYRROLIDINE-2,4-DICARBOXYLATE; ASTROCYTE COCULTURES; CEREBRAL-ISCHEMIA; NMDA ANTAGONISTS; SUBSTANTIA-NIGRA; CELL-CULTURE;
Keywords:
neuroprotection; glutamate pyruvate transaminase; alanine aminotransaminase; neuronal culture; L-trans-pyrrolidine-2,4-dicarboxylate;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
57
Recensione:
Indirizzi per estratti:
Indirizzo: Fishman, PS Univ Maryland, Dept Neurol, Sch Med, 22 S Green St, Baltimore,MD 21201 USA Univ Maryland 22 S Green St Baltimore MD USA 21201 D 21201 USA
Citazione:
C.C. Matthews et al., "Enzymatic degradation protects neurons from glutamate excitotoxicity", J NEUROCHEM, 75(3), 2000, pp. 1045-1052

Abstract

Several enzymes with the capacity to degrade glutamate have been suggestedas possible neuroprotectants. We initially evaluated the kinetic properties of glutamate pyruvate transaminase (GPT; also known as alanine aminotransferase), glutamine synthetase, and glutamate dehydrogenase under physiologic conditions to degrade neurotoxic concentrations of glutamate. Although all three enzymes initially degraded glutamate rapidly, only GPT was able to reduce toxic (500 mu M) levels of glutamate into the physiologic (<20 mu M)range. Primary cultures of fetal murine cortical neurons were subjected toparadigms of either exogenous or endogenous glutamate toxicity to evaluatethe neuroprotective value of GPT. Neuronal survival after exposure to added glutamate ranging from 100 to 500 mu M was improved significantly in the presence of GPT (greater than or equal to 1 U/ml), Cultures were also exposed to the glutamate transporter inhibitor L-trans-pyrrolidine-2,4-dicarboxylate (PDC), which produces neuronal injury by elevating extracellular glutamate, GPT significantly reduced the toxicity of PDC. This reduction was associated with a reduction in the PDC-dependent rise in the medium concentration of glutamate, These results suggest that enzymatic degradation of glutamate by GPT can be an alternative to glutamate receptor blockade as a strategy to protect neurons from excitotoxic injury.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/07/20 alle ore 08:57:22