Cooperative action of JNK and AKT/mTOR in 1-methyl-4-phenylpyridinium-induced autophagy of neuronal PC12 cells

Jezabel Rodríguez-Blanco, Vanesa Martín, Guillermo García-Santos, Federico Herrera, Sara Casado-Zapico, Isaac Antolín, Carmen Rodriguez

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Parkinson's disease has been widely related to both apoptosis and oxidative stress. Many publications relate the loss of mitochondrial potential to an apoptosis-mediated cell death in different in vivo and in vitro models of this pathology. The present study used the dopaminegic specific neurotoxin 1-methyl-4-phenylpyridinium (MPP+) on neuron-like PC12 cells, which is a well-accepted model of Parkinson's disease. Results showed an early increase in oxidants, which drives the modulation of c-Jun N-terminal kinase (JNK) and AKT/mammalian target of rapamycin (mTOR) pathways, mimicking peroxide treatment. However, the cell death found in neuronal PC12 cells treated with MPP+ was not a caspase-associated apoptosis. Electron microscopic images illustrated autophagic cell death, which was confirmed by a Beclin-1 and ATG expression increase, accumulation of acidic vesicles, and rescue by an autophagy inhibitor. In conclusion, the boost in oxidants from MPP+ treatment in neuronal PC12 is modulating both survival (AKT/mTOR) and death (JNK) pathways, which are the perpetrators of an autophagic cell death.

Original languageEnglish (US)
Pages (from-to)1850-1860
Number of pages11
JournalJournal of Neuroscience Research
Issue number9
StatePublished - Sep 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience


  • AKT
  • Autophagy
  • JNK
  • MPP
  • Neuronal PC12
  • Oxidative stress


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