Effects of aluminum exposure on glutamate metabolism: a possible explanation for its toxicity.
The effects of aluminum (Al) exposure on glutamate metabolism were investigated to study the mechanism of Al toxicity in rat brain. In astrocytes, the glutamate-glutamine pathway prevents the accumulation of the excitatory neurotransmitter glutamate, recognized as a neuronal excitotoxin when present in excess in the extracellular space. Changes in the level of l-aspartate, l-glutamate, and its metabolite l-glutamine were investigated in various regions of rat brains following intraperitoneal injection of aluminium gluconate for 2 months. The changes observed were area- and amino-acid-specific. An increase in glutamine, but not in l-glutamate or l-aspartate, was noted in the hippocampus and neocortex of Al-treated rats. This increase in vivo was consistent with observations in vitro. Exposure of cultured astrocytes to Al chloride (200, 400, and 800 microM) specifically increased glutamine synthetase activity for the three concentrations tested. In parallel with this increase, a higher rate of disappearance of glutamate from culture medium was observed during the first 10 min of incubation for the three concentrations tested, as well as an accumulation of glutamine in the cellular extract after 30 min. These observations indicate that the astrocyte population is a potential target for Al toxic action that could mediate the pathogenesis of this metal.
Struys-Ponsar
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C
Laboratoire de Biologie Cellulaire, Bâtiment Carnoy, 5 place Croix du Sud, Louvain-la-Neuve, B. 1348, Belgium.
Guillard
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O
van den Bosch de Aguilar
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P
D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002457:Cell Extracts; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism* / Q000493:pharmacokinetics; D005973:Glutamine / Q000378:metabolism; D020128:Inhibitory Concentration 50; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D009928:Organ Specificity; D051381:Rats
D002457:Cell Extracts; D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; D000535:Aluminum; D007770:L-Lactate Dehydrogenase; D005974:Glutamate-Ammonia Ligase