Cycloheximide and actinomycin D block the toxic effect of glutamic acid on PC12 cells.

Programmed cell death is considered to play a key role during development and also during physiopathological events such as neurodegenerative diseases and ischaemia. We have recently shown in PC12 cells that glutamate induces a progressive cytotoxicity which is only visible 8-10 h after incubation with glutamate for at least 4-6 h. We now present evidence that the toxic action of glutamate may correspond to programmed cell death because it is blocked by either actinomycin D or cycloheximide. This effect, however, may not be due to apoptosis since it is not blocked by aurintricarboxylic acid, a non-specific inhibitor of endonucleases, and neither chromatin condensation nor DNA fragmentation or liberation is seen after glutamate treatment.