SSeCKS promote beta-amyloid-induced PC12 cells neurotoxicity by up-regulating tau phosphorylation in Alzheimer's disease.
In Alzheimer's disease, beta-amyloid peptide (Abeta) could induce tau hyperphosphorylation which is the major cause of neuron apoptosis. However, the underlying mechanisms in the process remain unclear. In this study, Abeta-induced apoptosis and tau phosphorylation were investigated in differentiated PC12 cells. This Abeta-induced tau phosphorylation paralleled with the increase of expression and phosphorylation of Src-suppressed protein kinase C substrate (SSeCKS). By knocking down the expression of SSeCKS, Abeta-induced apoptosis and tau hyperphosphorylation in PC12 cells were partially rescued, and were increased further due to the overexpression of SSeCKS in PC12 cells. Also, the cell apoptosis and tau hyperphosphorylation were strongly decreased when the cells were pretreated with the protein kinase C inhibitor, Gö6983. In addition, Abeta-induced tau phosphorylation was also partially decreased due to the overexpression of SSeCKS in PC12cells. In summary, our data indicate that SSeCKS may play a critical role in Abeta-induced PC12 cells apoptosis through its phosphorylation.
Department of Osteology, The Second Affiliated Hospital of Nantong University, Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, People's Republic of China.
Zhiming
Z
Cui
Tao
T
Tao
Chun
C
Cheng
Junling
J
Yang
Qin
Q
Shen
Yuhong
Y
Ji
Xiaohong
X
Li
Haiou
H
Liu
Aiguo
A
Shen
Xiang
X
Lu
D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D007211:Indoles; D008301:Maleimides; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016716:PC12 Cells; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D051381:Rats; D014162:Transfection; D015854:Up-Regulation; D016875:tau Proteins / Q000378:metabolism*
C465664:2-(1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl)-3-(1H-indol-3-yl)maleimide; D054758:A Kinase Anchor Proteins; C102361:Akap12 protein, rat; D016229:Amyloid beta-Peptides; D002227:Carbazoles; D018797:Cell Cycle Proteins; D007211:Indoles; D008301:Maleimides; C489131:Mapt protein, rat; D047428:Protein Kinase Inhibitors; D016875:tau Proteins; D011493:Protein Kinase C