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

Abstract
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.
AuthorsF Vimard, M Saucet, O Nicole, M Feuilloley, D Duval
JournalJournal of biochemical and molecular toxicology (J Biochem Mol Toxicol) 2011 Jul-Aug Vol. 25 Issue 4 Pg. 205-15 ISSN: 1099-0461 [Electronic] United States
PMID21812070 (Publication Type: Journal Article)
CopyrightCopyright © 2011 Wiley Periodicals, Inc.
Chemical References
  • Actins
  • Alkylating Agents
  • Antioxidants
  • Benzene Derivatives
  • Buthionine Sulfoximine
  • Mercaptoethanol
  • Adenosine Triphosphate
  • Glutathione
  • Ethylmaleimide
  • cumene hydroperoxide
  • Calcium
  • Acetylcysteine
Topics
  • Acetylcysteine (pharmacology)
  • Actins (metabolism)
  • Adenosine Triphosphate (metabolism)
  • Alkylating Agents (pharmacology)
  • Animals
  • Antioxidants (pharmacology)
  • Benzene Derivatives (toxicity)
  • Buthionine Sulfoximine (pharmacology)
  • Calcium (metabolism)
  • Cell Shape
  • Cell Survival (drug effects)
  • Cytoprotection
  • Dose-Response Relationship, Drug
  • Ethylmaleimide (pharmacology)
  • Glutathione (antagonists & inhibitors, metabolism)
  • Membrane Potential, Mitochondrial
  • Mercaptoethanol (pharmacology)
  • Oxidative Stress (drug effects)
  • PC12 Cells
  • Rats

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