p62 protects SH-SY5Y neuroblastoma cells against H2O2-induced injury through the PDK1/Akt pathway.

The p62 protein has been identified as a major component of the protein aggregations associated with neurodegenerative disease. Oxidative insult has also been identified as a principal cause of neurodegenerative disease. Thus, in the present study, we investigated the potential role of p62 in oxidative stress-induced cell death in SH-SY5Y ...
human neuroblastoma cells. The results indicated that H(2)O(2) treatment induced p62 expression in SH-SY5Y cells. In addition, p62 showed neuroprotective effects against H(2)O(2)-induced cell death in differentiated SH-SY5Y cells. p62 expression prolonged Akt phosphorylation during the later stages of H(2)O(2)-induced cell death. Furthermore, coexpression of p62 and wild-type PDK1, the upstream kinase of Akt, further increased Akt phosphorylation and cell viability, whereas the expression of kinase-defective PDK1 reversed the cytoprotective effects of p62 under oxidative stress. Overexpression of p62 led to the dissociation of PDK1 from the 14-3-3theta protein, which is thought to be a negative regulator of PDK1 kinase activity. These findings suggest a mechanism that involves the p62-mediated modulation of the interaction between signaling molecules and results in cell survival.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Blotting, Western, Cell Line, Tumor, Cell Survival, Chromones, Enzyme Inhibitors, Gene Expression, Humans, Hydrogen Peroxide, Morpholines, Neurons, Oxidative Stress, Phosphatidylinositol 3-Kinases, Phosphorylation, Protein Kinase C, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins c-akt, Signal Transduction, Transfection
Neurosci. Lett.
Date: Jan. 23, 2009
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