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Toxicity induced by cumene hydroperoxide in PC12 cells: Protective role of thiol donors
Author(s) -
Vimard F.,
Saucet M.,
Nicole O.,
Feuilloley M.,
Duval D.
Publication year - 2010
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.20377
Subject(s) - cumene hydroperoxide , glutathione , chemistry , programmed cell death , intracellular , microbiology and biotechnology , buthionine sulfoximine , reactive oxygen species , cell , oxidative stress , cumene , oxidative phosphorylation , mitochondrion , biochemistry , biophysics , apoptosis , biology , enzyme , catalysis
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. © 2011 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:205–215, 2011; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.20377