Toxicity induced by cumene hydroperoxide in PC12 cells: Protective role of thiol donors
J. Biochem. Mol. Toxicol.. 2010-12-01; 25(4): 205-215
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1. J Biochem Mol Toxicol. 2011 Jul-Aug;25(4):205-15. doi: 10.1002/jbt.20377. Epub
2010 Dec 1.
Toxicity induced by cumene hydroperoxide in PC12 cells: protective role of thiol
Vimard F(1), Saucet M, Nicole O, Feuilloley M, Duval D.
(1)CNRS UMR 6232 CINAPS, Centre Cyceron, BP 5229, 14074 Caen cedex, France.
Oxidative shock and production of reactive oxygen species are known to play a
major role in situations leading to neuron degeneration, but the precise
mechanisms responsible for cell degeneration remain uncertain. In the present
article, we have studied in PC 12 cells the effect of cumene hydroxyperoxide on
both cell metabolism and morphology. We observed that relatively low
concentrations of the drug (100 μM) led to a significant decrease in the cellular
content of ATP and reduced glutathione as well as to a decreased mitochondrial
potential. These metabolic alterations were followed by an important increase in
intracellular free calcium and membrane disruption and death. In parallel, we
observed profound changes in cell morphology with a shortening of cell
extensions, the formation of ruffles and blebs at the cell surface, and a
progressive detachment of the cells from the surface of the culture flasks. We
also showed that addition of thiol donors such as N-acetylcysteine or
β-mercaptoethanol, which were able to enhance cell glutathione content, almost
completely protected PC 12 cells from the toxic action of cumene hydroperoxide
whereas pretreatment by buthionine sulfoximine, a selective inhibitor of GSH
synthesis, enhanced its action.
Copyright © 2011 Wiley Periodicals, Inc.
PMID: 21812070 [Indexed for MEDLINE]