Glutamate triggers internucleosomal DNA cleavage in neuronal cells.
Glutamate neurotoxicity is responsible for neuronal loss associated with numerous obstinate disorders. In this report, the mechanism of glutamate neurotoxicity was investigated on a viewpoint of DNA degradation. We found that chromosomal DNA of cultured neurons was degraded into nucleosomal-sized DNA fragments by the addition of glutamate, prior to the glutamate-induced neuronal death. Both the neuronal death and DNA fragmentation were prevented by the inhibitors of endonucleases and mRNA synthesis. Furthermore, an injection of glutamate into the rat hippocampi resulted in DNA fragmentation with the similar time course observed in neuronal death in vitro. These results suggest that the glutamate neurotoxicity involves an active suicide process which leads to neuronal death through internucleosomal DNA cleavage.
Department of Biochemical Genetics, Tohoku University School of Medicine, Sendai, Japan.
S
S
Kure
T
T
Tominaga
T
T
Yoshimoto
K
K
Tada
K
K
Narisawa
D000818:Animals; D001312:Aurintricarboxylic Acid / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000502:physiology; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D003609:Dactinomycin / Q000494:pharmacology; D005333:Fetus; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D007700:Kinetics; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology*; D009707:Nucleosomes / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D005971:Glutamates; D009498:Neurotoxins; D009707:Nucleosomes; D003609:Dactinomycin; D018698:Glutamic Acid; D001312:Aurintricarboxylic Acid; D004247:DNA