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 journalArticle

40 Citations (Scopus)

Abstract

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
Volume36
Issue number6
DOIs
StatePublished - May 1 2000
Externally publishedYes

Fingerprint

1-Methyl-4-phenylpyridinium
Glutathione Disulfide
Pheochromocytoma
Rotenone
Glutathione
Oxygen
Oxidation-Reduction
Neurotoxins
Homeostasis
Acids

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Seyfried, J., Soldner, F., Kunz, W. S., Schulz, J. B., Klockgether, T., Kovar, K. A., & Wüllner, U. (2000). Effect of 1-methyl-4-phenylpyridinium on glutathione in rat pheochromocytoma PC 12 cells. Neurochemistry International, 36(6), 489-497. https://doi.org/10.1016/S0197-0186(99)00156-4

Effect of 1-methyl-4-phenylpyridinium on glutathione in rat pheochromocytoma PC 12 cells. / Seyfried, Jan; Soldner, Frank; Kunz, Wolfram S.; Schulz, Jörg B.; Klockgether, Thomas; Kovar, Karl A.; Wüllner, Ullrich.

In: Neurochemistry International, Vol. 36, No. 6, 01.05.2000, p. 489-497.

Research output: Contribution to journalArticle

Seyfried, J, Soldner, F, Kunz, WS, Schulz, JB, Klockgether, T, Kovar, KA & Wüllner, U 2000, 'Effect of 1-methyl-4-phenylpyridinium on glutathione in rat pheochromocytoma PC 12 cells', Neurochemistry International, vol. 36, no. 6, pp. 489-497. https://doi.org/10.1016/S0197-0186(99)00156-4
Seyfried, Jan ; Soldner, Frank ; Kunz, Wolfram S. ; Schulz, Jörg B. ; Klockgether, Thomas ; Kovar, Karl A. ; Wüllner, Ullrich. / Effect of 1-methyl-4-phenylpyridinium on glutathione in rat pheochromocytoma PC 12 cells. In: Neurochemistry International. 2000 ; Vol. 36, No. 6. pp. 489-497.
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