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

Abstract

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.

• Authors: Jezabel Rodríguez-Blanco, Vanesa Martín, Guillermo García-Santos, Federico Herrera, Sara Casado-Zapico, Isaac Antolín, Carmen Rodriguez
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 90 Issue 9 Pg. 1850-60 (Sep 2012) ISSN: 1097-4547 [Electronic] United States
• PMID: 22513717 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Wiley Periodicals, Inc.

Chemical References

• Neurotoxins
• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases
• MAP Kinase Kinase 4

Topics

• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (pharmacology)
• Animals
• Autophagy (physiology)
• Blotting, Western
• MAP Kinase Kinase 4 (metabolism)
• Neurons (drug effects, metabolism)
• Neurotoxins (toxicity)
• Oxidative Stress (physiology)
• PC12 Cells
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Signal Transduction (physiology)
• TOR Serine-Threonine Kinases (metabolism)