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Delayed application of aurintricarboxylic acid reduces glutamate‐induced cortical neuronal injury
Author(s) -
Csernansky C. A.,
Canzoniero L. M. T.,
Sensi S. L.,
Yu S. P.,
Choi D. W.
Publication year - 1994
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490380113
Subject(s) - aurintricarboxylic acid , glutamate receptor , neuroprotection , neurotoxicity , nmda receptor , intracellular , glutamic acid , excitotoxicity , biology , programmed cell death , microbiology and biotechnology , biochemistry , chemistry , pharmacology , receptor , apoptosis , amino acid , toxicity , organic chemistry
The non‐specific endonuclease inhibitor, aurintricarboxylic acid (ATA), attenuated glutamate‐induced destruction of cultured cortical neurons. In part, this protective effect likely reflected the ability of ATA to produce a slowly developing block of N ‐methyl‐ D ‐aspartate receptor‐mediated inward whole cell current or increase in intracellular free Ca 2+ . However, ATA also attenuated a high K + ‐induced increase in intracellular free Ca 2+ in the presence of D‐aminophosphonovalerate, suggesting that ATA may have a more general effect on Ca 2+ homeostasis. In addition, ATA attenuated glutamate neurotoxicity even if added up to 2 hr after completion of glutamate exposure, a time when glutamate antagonists or lipid peroxidation inhibitors are no longer neuroprotective. Involvement of apoptosis in this excitotoxic death is unlikely, as Southern blotting of genomic DNA revealed no evidence of fragmentation, and death was not prevented by inhibitors of RNA or protein synthesis. Most likely, ATA interferes with some key downstream consequences of excitotoxic glutamate receptor overactivation. © 1994 Wiley‐Liss, Inc.