Premium
Cooperative action of JNK and AKT/mTOR in 1‐methyl‐4‐phenylpyridinium‐induced autophagy of neuronal PC12 cells
Author(s) -
RodríguezBlanco Jezabel,
Martín Vanesa,
GarcíaSantos Guillermo,
Herrera Federico,
CasadoZapico Sara,
Antolín Isaac,
Rodriguez Carmen
Publication year - 2012
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23066
Subject(s) - autophagy , pi3k/akt/mtor pathway , protein kinase b , programmed cell death , microbiology and biotechnology , apoptosis , chemistry , kinase , biology , cancer research , signal transduction , biochemistry
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. © 2012 Wiley Periodicals, Inc.