Toxicity induced by cumene hydroperoxide in PC12 cells: Protective role of thiol donors

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 hydroxyper...

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Bibliographic Details
Published in:Journal of biochemical and molecular toxicology 2011-07, Vol.25 (4), p.205-215
Main Authors: Vimard, F., Saucet, M., Nicole, O., Feuilloley, M., Duval, D.
Format: Article
Language:English
Subjects:
Acetylcysteine
Acetylcysteine - pharmacology
Actins - metabolism
Adenosine Triphosphate - metabolism
Alkylating Agents - pharmacology
Alterations of the Cytoskeleton
Animals
Antioxidants - pharmacology
ATP
Benzene Derivatives - toxicity
Buthionine sulfoximine
Buthionine Sulfoximine - pharmacology
Calcium (intracellular)
Calcium - metabolism
Cell culture
Cell Shape
Cell Survival - drug effects
cumene hydroperoxide
Cytology
Cytoprotection
Degeneration
Dose-Response Relationship, Drug
Drugs
Ethylmaleimide - pharmacology
Evolution of Cytosolic Calcium
Glutathione
Glutathione - antagonists & inhibitors
Glutathione - metabolism
Glutathione Depletion
Internet
Membrane Potential, Mitochondrial
Mercaptoethanol - pharmacology
Metabolism
Mitochondria
Neurons
Oxidative Stress - drug effects
PC12 Cells
Peroxide Toxicity
Pheochromocytoma cells
Protective Effect of N-Acetylcysteine and -Mercaptoethanol
Rats
Reactive oxygen species
Shock
Thiols
Toxicity
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Summary: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
ISSN:1095-6670
1099-0461
DOI:10.1002/jbt.20377