Transcriptional or translational inhibition blocks low dose NMDA-mediated cell death.
Glutamate toxicity in nerve cells has been well documented and may play a role in a broad spectrum of neurological and ophthalmic diseases. Recent work in several laboratories has suggested that an apoptotic-like mechanism may be implicated in glutamate toxicity under certain circumstances. We therefore studied the effects of transcriptional and translational inhibition on glutamate-mediated cell death in retinal ganglion cells. We now report that either cycloheximide or actinomycin D can, even when added 2 h after the initial excitotoxic insult, save retinal ganglion cells from low dose glutamate toxicity. However, cycloheximide or actinomycin D are unable to prevent glutamate-mediated death at higher concentrations of excitotoxin. This result indicates that at low doses, the neurotoxic effects of glutamate may develop through an apoptotic-like mechanism.
Dreyer
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EB
Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.
Zhang
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D
Lipton
S A
SA
D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000633:toxicity; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000633:toxicity*; D014176:Protein Biosynthesis / Q000187:drug effects*; D051381:Rats; D012165:Retinal Ganglion Cells / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects*
D018691:Excitatory Amino Acid Antagonists; D003609:Dactinomycin; D018698:Glutamic Acid; D016202:N-Methylaspartate; D003513:Cycloheximide