V. Castagne et Pgh. Clarke, COOPERATION BETWEEN GLUTATHIONE DEPLETION AND PROTEIN-SYNTHESIS INHIBITION AGAINST NATURALLY-OCCURRING NEURONAL DEATH, Neuroscience, 86(3), 1998, pp. 895-902
It is generally agreed that naturally-occurring neuronal death in deve
loping animals is dependent on the synthesis of proteins. Oxidative st
ress, as when intracellular concentrations of free radicals are raised
or when cell constituents such as membrane lipids or protein thiols a
re oxidized, is also involved in various types of neuronal death. In t
he present report, we show that the number of naturally dying retinal
cells in the chick embryo can be reduced by intraocular injections of
cycloheximide, an inhibitor of protein synthesis. L-buthionine-[S,R]-s
ulfoximine, an inhibitor of glutathione synthesis, can either enhance
or diminish the cell death, depending on the conditions of treatment.
Moreover, when the two inhibitors are combined, L-buthionine-[S.R]-sul
foximine potentiates the neuroprotective effects of cycloheximide. Mea
surements of retinal glutathione concentration and protein synthesis s
how the specificity of the treatments: buthionine-sulfoximine diminish
es glutathione concentrations but not protein synthesis whereas cycloh
eximide inhibits protein synthesis without decreasing glutathione conc
entrations. Naturally-occurring neuronal death thus seems to involve t
he synthesis of proteins, and is also influenced by oxidative phenomen
a. Our results extend previous data in tectal-lesioned embryos, and su
ggest that a moderate, non-lethal oxidative stress can enhance the res
istance of ganglion cells that might otherwise have died (spontaneousl
y or following axotomy) owing to insufficient retrograde trophic suppo
rt. (C) 1998 IBRO. Published by Elsevier Science Ltd.