Effect of 1-methyl-4-phenylpyridinium on glutathione in rat pheochromocytoma PC 12 cells

Jan Seyfried, Frank Soldner, Wolfram S. Kunz, Jörg B. Schulz, Thomas Klockgether, Karl A. Kovar, Ullrich Wüllner

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


We investigated the effect of the selective dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP+) on glutathione redox status and the generation of reactive oxygen intermediates (ROI) in rat pheochromocytoma PC 12 cells in vitro. Treatment with MPP+ (250 μM) led to a 63% increase of reduced glutathione (GSH) after 24 h, while a 10-fold higher concentration of MPP+ (2.5 mM) depleted cellular GSH to 12.5% of control levels within that time. Similarly, the complex I-inhibitor rotenone induced a time-dependent loss of GSH at 1 and 10 μM, whereas treatment with lower concentrations of rotenone (0.1, 0.01 μM) increased cellular GSH. Both MPP+ and rotenone increased cellular levels of oxidised glutathione (GSSG) and the higher concentrations of both compounds led to an elevated ratio of oxidised glutathione (GSSG) vs total glutathione (GSH+GSSG) indicating a shift in cellular redox balance. MPP+ or rotenone did not induce the generation of ROI or significant elevation of intracellular levels of thiobabituric acid reactive substances (TBARS) for up to 48 h. Our data suggest that MPP+ has differential effects on glutathione homeostasis depending on the degree of complex I-inhibition and that inhibition of complex I is not sufficient to generate ROI in this paradigm. Copyright (C) 2000 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)489-497
Number of pages9
JournalNeurochemistry International
Issue number6
StatePublished - May 2000
Externally publishedYes


  • 1-methyl-4-phenylpyridinium
  • Glutathione
  • Rat pheochromocytoma PC 12 cells
  • Reactive oxygen intermediates

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology


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