PMID- 10762085
OWN - NLM
STAT- MEDLINE
DCOM- 20000511
LR  - 20191210
IS  - 0197-0186 (Print)
IS  - 0197-0186 (Linking)
VI  - 36
IP  - 6
DP  - 2000 May
TI  - Effect of 1-methyl-4-phenylpyridinium on glutathione in rat pheochromocytoma PC 
      12 cells.
PG  - 489-97
AB  - 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 microM) 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 
      microM, whereas treatment with lower concentrations of rotenone (0.1, 0.01 
      microM) 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.
FAU - Seyfried, J
AU  - Seyfried J
AD  - Department of Neurology, University of Tubingen, Germany. 
      jan.seyfried@uni-tuebingen.de
FAU - Soldner, F
AU  - Soldner F
FAU - Kunz, W S
AU  - Kunz WS
FAU - Schulz, J B
AU  - Schulz JB
FAU - Klockgether, T
AU  - Klockgether T
FAU - Kovar, K A
AU  - Kovar KA
FAU - Wullner, U
AU  - Wullner U
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Neurochem Int
JT  - Neurochemistry international
JID - 8006959
RN  - 0 (Dopamine Agents)
RN  - 0 (Reactive Oxygen Species)
RN  - 03L9OT429T (Rotenone)
RN  - 9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
RN  - EC 1.6.- (NADH, NADPH Oxidoreductases)
RN  - EC 7.1.1.2 (Electron Transport Complex I)
RN  - GAN16C9B8O (Glutathione)
RN  - ULW86O013H (Glutathione Disulfide)
SB  - IM
MH  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/*pharmacology
MH  - Animals
MH  - Dopamine Agents/*pharmacology
MH  - Electron Transport Complex I
MH  - Glutathione/*metabolism
MH  - Glutathione Disulfide/metabolism
MH  - NADH, NADPH Oxidoreductases/antagonists & inhibitors
MH  - Oxidation-Reduction
MH  - PC12 Cells
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Rotenone/pharmacology
EDAT- 2000/04/13 09:00
MHDA- 2000/05/16 09:00
CRDT- 2000/04/13 09:00
PHST- 2000/04/13 09:00 [pubmed]
PHST- 2000/05/16 09:00 [medline]
PHST- 2000/04/13 09:00 [entrez]
AID - S0197-0186(99)00156-4 [pii]
AID - 10.1016/s0197-0186(99)00156-4 [doi]
PST - ppublish
SO  - Neurochem Int. 2000 May;36(6):489-97. doi: 10.1016/s0197-0186(99)00156-4.