Premium
Enzymatic Degradation Protects Neurons from Glutamate Excitotoxicity
Author(s) -
Matthews Christopher C.,
Zielke H. Ronald,
Wollack Jan B.,
Fishman Paul S.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0751045.x
Subject(s) - excitotoxicity , glutamate receptor , chemistry , neuroscience , enzyme , degradation (telecommunications) , biochemistry , biology , computer science , receptor , telecommunications
Several enzymes with the capacity to degrade glutamate have been suggested as 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 μ M ) levels of glutamate into the physiologic (<20 μ M ) range. Primary cultures of fetal murine cortical neurons were subjected to paradigms of either exogenous or endogenous glutamate toxicity to evaluate the neuroprotective value of GPT. Neuronal survival after exposure to added glutamate ranging from 100 to 500 μ M was improved significantly in the presence of GPT (≥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.