title: Neuroprotective effects of new protein kinase C activator TPPB against Aβ₂₅₋₃₅ induced neurotoxicity in PC12 cells.
abstract: Alzheimer's disease (AD) is pathologically characterized by presence of senile plaques in the hippocampus, which are composed mainly of extracellular deposition of a polypeptide known as the beta amyloid, the Aβ. It has been demonstrated on numerous occasions that it was the deposition and aggregation of this Aβ peptide that cause neuronal dysfunction and even finally, the dementia. Lowering the deposition of Aβ or decreasing its neurotoxicity has long been one of the purposes of AD therapy. In previous study, we reported that protein kinase C (PKC) activator TPPB could regulate APP processing by increasing α-secretase activity. In this study we further investigated the potential neuroprotective effect of TPPB against Aβ(25-35)-induced neurotoxicity in PC12 cells. The results indicated that TPPB at concentration of 1 μM could antagonize Aβ(25-35) induced cell damage as evidenced by MTT assays, LDH release and by morphological changes. Furthermore, the neuroprotection in cell viability can be blocked by inhibitors of PKC, Akt and MAPK. The experiment also indicated that TPPB could increase the phosphorylation of Akt, PKC, MARCKS and MAPK, which were inhibited by Aβ(25-35) treatment. Finally, TPPB inhibited the activation of caspase-3 induced by Aβ(25-35). Taken together, the experiment here implies that TPPB has a role against Aβ(25-35)-induced neurotoxicity in PC12 cells and may suggest its therapeutic potential in AD.
authors: Department of Neurology, Henan Provincial People's Hospital, Zhengzhou 450003, Henan Province, People's Republic of China. ericyng@163.com
authors: Hong-Qi
authors: HQ
authors: Yang
authors: Xue
authors: X
authors: Li
authors: Wei-Min
authors: WM
authors: Yang
authors: Shu-Man
authors: SM
authors: Feng
authors: Jian-Jun
authors: JJ
authors: Ma
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D016716:PC12 Cells; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats
chemical_list: C121197:2-(2-(triphenylphosphonio)ethyl)-3,4-dihydro-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol bromide; D016229:Amyloid beta-Peptides; D001578:Benzopyrans; D020536:Enzyme Activators; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; D053148:Caspase 3