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Titolo:
Methionine sulfoximine shows excitotoxic actions in rat cortical slices
Autore:
Shaw, CA; Bains, JS; Pasqualotto, BA; Curry, K;
Indirizzi:
Univ British Columbia, Dept Anat, Dept Ophthalmol, Vancouver, BC V6T 1Z3, Canada Univ British Columbia Vancouver BC Canada V6T 1Z3 ver, BC V6T 1Z3, Canada Univ British Columbia, Dept Anat, Dept Physiol, Vancouver, BC V6T 1Z3, Canada Univ British Columbia Vancouver BC Canada V6T 1Z3 ver, BC V6T 1Z3, Canada Univ British Columbia, Dept Anat, Neurosci Program, Vancouver, BC V6T 1Z3,Canada Univ British Columbia Vancouver BC Canada V6T 1Z3 uver, BC V6T 1Z3,Canada Precis Biochem, Vancouver, BC V6T 1Z3, Canada Precis Biochem Vancouver BCCanada V6T 1Z3 Vancouver, BC V6T 1Z3, Canada
Titolo Testata:
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
fascicolo: 11, volume: 77, anno: 1999,
pagine: 871 - 877
SICI:
0008-4212(199911)77:11<871:MSSEAI>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMYOTROPHIC-LATERAL-SCLEROSIS; METHYL-D-ASPARTATE; NEURODEGENERATIVE DISORDERS; ALZHEIMER-DISEASE; OXIDATIVE STRESS; CEREBRAL-CORTEX; GLUTATHIONE; BRAIN; ACID; METABOLISM;
Keywords:
agene process; glutamate release; lactate dehydrogenase; methionine sulfoximine; N-methyl-D-aspartate (NMDA) receptor; neurological disorders;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Shaw, CA Univ British Columbia, Dept Anat, Dept Ophthalmol, 2177 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada Univ British Columbia 2177 Wesbrook Mall Vancouver BC Canada V6T 1Z3
Citazione:
C.A. Shaw et al., "Methionine sulfoximine shows excitotoxic actions in rat cortical slices", CAN J PHYSL, 77(11), 1999, pp. 871-877

Abstract

Methionine sulfoximine (MSO) is a rare amino acid. It occurs in nature or as a by-product of some forms of food processing. A notable example of the latter was a former method for bleaching wheat flour, using nitrogen trichloride, the "agene process," in use for most of the first 50 years of this century. "Agenized" flour was found to be responsible for various neurological disorders in animals, and MSO was identified as the toxic factor. The agene process was subsequently discontinued in the United States and the United Kingdom circa 1950. MSO inhibits the synthesis of both glutathione and glutamine, and it is possible that its actions on the nervous system arise from alterations in the amount or distribution of these molecules. Structurally, MSO resembles glutamate, an observation that has also raised the possibility that it might have more direct glutamate-like actions on neurons. Inthe present investigation, we report excitatory and toxic actions of MSO in an in vitro preparation of adult rat cortex. Field potential recordings in this preparation show that MSO application evokes a sustained depolarization, which can be blocked by the N-methyl-D-aspartate (NMDA) antagonist L-()-2-amino-5-phosphonovalerate (AP5). However, competition assays using MSOon [H-3]CGP-39653 (DL-(E)-2-amino-4-propyl-1-phosphono-3-pentenoate) binding in rat cortical homogenates show only 20% displacement of total binding,suggesting that MSO is acting indirectly, perhaps by releasing glutamate. To investigate this possibility, we measured glutamate release during MSO application. Time course and dose-response experiments with MSO showed significant [H-3]glutamate release, which was partially attenuated by AP5. To assess cellular toxicity, we measured lactate dehydrogenase (LDH) release from cortical sections exposed to MSO. MSO treatment led to a rapid increase in LDH activity, which could be blocked by AP5. These data suggest that MSO acts by increasing glutamate release, which then activates NMDA receptors, leading to excitotoxic cell death. These data suggest the possibility that MSO in processed flour had excitotoxic actions that may have been contributing factors to some human neuronal disorders.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/01/20 alle ore 12:28:15