1-Methyl-4-phenylpyridinum kills differentiated PC12 cells with a concomitant change in protein phosphorylation.
1-Methyl-4-phenylpyridinum (MPP+), a selective neurotoxin, destroys the dopaminergic nigrostriatal pathway and results in a parkinsonian syndrome. Exposure of differentiated PC12 cells with nerve growth factor for 5 days to MPP+ (100 microM) for 4 h induced DNA fragmentation which is typical for the programmed cell death. MPP+ treatment (100 microM) concomitantly stimulates S6 kinase activity and resultant phosphorylation of S6 protein of 40S ribosomal subunits in the cells. Cycloheximide treatment prevents the MPP(+)-induced DNA fragmentation and enhancement of the phosphorylation of S6 protein. The present data demonstrate that neurotoxin, MPP+, kills differentiated PC12 cells by the apparent involvement of apoptotic process. Furthermore, the data strongly suggest that a change in protein phosphorylation might be involved in the signal transduction of MPP+ neurotoxicity and/or the protection from its toxicity.
Second Department of Internal Medicine, Fukui Medical School, Japan.
T
T
Mutoh
A
A
Tokuda
A M
AM
Marini
N
N
Fujiki
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D002454:Cell Differentiation; D004273:DNA, Neoplasm / Q000032:analysis / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D004789:Enzyme Activation; D007700:Kinetics; D009414:Nerve Growth Factors / Q000494:pharmacology; D016716:PC12 Cells; D010710:Phosphates / Q000378:metabolism; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D019893:Ribosomal Protein S6 Kinases; D012270:Ribosomes / Q000378:metabolism
D004273:DNA, Neoplasm; D009414:Nerve Growth Factors; D010710:Phosphates; D010750:Phosphoproteins; D010761:Phosphorus Radioisotopes; D000255:Adenosine Triphosphate; D017346:Protein Serine-Threonine Kinases; D019893:Ribosomal Protein S6 Kinases; D015655:1-Methyl-4-phenylpyridinium