Inhibition of glutathione synthesis can enhance cycloheximide-induced protection of developing neurons against axotomy.

Details

Serval ID
serval:BIB_79107B3DBBC3
Type
Article: article from journal or magazin.
Collection
Publications
Title
Inhibition of glutathione synthesis can enhance cycloheximide-induced protection of developing neurons against axotomy.
Journal
Brain Research. Developmental Brain Research
Author(s)
Castagné V., Clarke P.G.H.
ISSN
0165-3806[print], 0165-3806[linking]
Publication state
Published
Issued date
1997
Volume
102
Number
2
Pages
285-290
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Developing neurons depend for survival on target-derived trophic substances. These are thought to block the expression of a genetic program of cell death. Nevertheless, it is known that less orderly events such as oxidative stress are involved in neuron death. In vivo, retinal ganglion cell death induced by axotomy can be reduced by antioxidants. In this study, we investigated the effects of inhibiting glutathione synthesis by means of buthionine sulfoximine to characterize the influence of endogenous glutathione-dependent antioxidant systems on ganglion cell death. Moreover, since protein synthesis inhibition by cycloheximide has been shown to enhance glutathione synthesis in vitro, we studied the effects on cell death of intraocular injections of buthionine sulfoximine, cycloheximide and combinations of the two inhibitors. Cycloheximide's protective action did not seem to involve an increase in glutathione synthesis. Surprisingly, buthionine sulfoximine injected before cycloheximide enhanced its protective effects, whereas it inhibited them when injected later. We interpret our results as an interaction between death-promoting effects of glutathione depletion through an elevation of free radical concentrations and cycloheximide-sensitive effects of oxidative stress through the synthesis of both death-inhibiting and death-promoting proteins.
Keywords
Animals, Axotomy, Buthionine Sulfoximine/pharmacology, Cell Death/drug effects, Chick Embryo, Cycloheximide/pharmacology, Glutathione/biosynthesis, Neurons/drug effects, Neurons/metabolism, Neuroprotective Agents/pharmacology, Oxidative Stress/drug effects, Protein Synthesis Inhibitors/pharmacology
Pubmed
Create date
20/01/2008 18:49
Last modification date
20/08/2019 15:35
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