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.
Heo
Seong Ryong
SR
Department of Biological Sciences, Hanseo University, Seosan, Chungnam 356-706, Republic of Korea.
Han
Ah Mi
AM
Kwon
Yunhee Kim
YK
Joung
Insil
I
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; C000631429:PDK1 protein, human; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D006861:Hydrogen Peroxide; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C