1-Methyl-4-phenylpyridinum kills differentiated PC12 cells with a concomitant change in protein phosphorylation

Tatsuro Mutoh, Akira Tokuda, Ann M. Marini, Norio Fujiki

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30 Citations (Scopus)


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 μM) for 4 h induced DNA fragmentation which is typical for the programmed cell death. MPP+ treatment (100 μM) 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.

Original languageEnglish
Pages (from-to)51-55
Number of pages5
JournalBrain Research
Issue number1-2
Publication statusPublished - 24-10-1994
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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