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.
Original language | English (US) |
---|---|
Pages (from-to) | 1850-1860 |
Number of pages | 11 |
Journal | Journal of Neuroscience Research |
Volume | 90 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2012 |
Externally published | Yes |
All Science Journal Classification (ASJC) codes
- Cellular and Molecular Neuroscience
Keywords
- AKT
- Autophagy
- JNK
- MPP
- Neuronal PC12
- Oxidative stress