Protein S-thiolation can mediate the inhibition of protein synthesis induced by tert-butyl hydroperoxide in isolated rat hepatocytes.
Latour I, De Ros E, Denef JF, Buc Calderon P
Metabolisme, Universite Catholique de Louvain, Bruxelles, 1200, Belgium.
A rapid inhibition of protein synthesis is observed when isolated rat
hepatocytes are incubated in the presence of 0.25-0.5 mM of tert-butyl
hydroperoxide (tBOOH). Such an inhibition occurs in the absence of a cytolytic
effect by tBOOH. Iron chelators (o-phenanthroline and desferrioxiamine),
protected against oxidative cell death, but they did not modify the inhibition
of protein synthesis caused by tBOOH (0.5 mM), suggesting that free radicals
are less implicated in such an impairment. Electron micrographs of hepatocytes
under oxidative stress show disaggregation of polyribosomes but not oxidative
alterations, such as blebs or mitochondrial swelling. Protein synthesis
inhibition is accompanied by a decrease in reduced glutathione (GSH) and
an increase in glutathione disulfide (GSSG) and the level of protein S-thiolation
(protein mixed disulfides formation). Such an increase of GSSG appears
as a critical event since diethylmaleate (DEM) at 0.2 mM reduced GSH content
by more than 50% but did not affect either GSSG content or protein synthesis.
The addition of exogenous GSH and N-acetylcysteine (NAC) to tBOOH-treated
hepatocytes significantly reduced the formation of protein mixed disulfides
and restored the depressed protein synthesis either completely or partially.
We suggest that S-thiolation of some key proteins may be involved in protein
synthesis inhibition by tBOOH. Copyright 1999 Academic Press.
PMID: 10502497, UI: 99434219