[Study of the protection and mechanism of IGF-1 on tau protein hyperphosphorylation in PC12 cells induced by Abeta(1-40)].
OBJECTIVE
To investigate the effect and the molecular mechanism of insulin-like growth factor 1 (IGF-1) on the level of tau protein phosphorylation in PC12 cells induced by aggregated beta-amyloid protein(1-40) (Abeta(1-40)).


METHODS
MTT assay was used to measure the survival rate of PC12 cells, Western blot was applied to detect tau phosphorylation level, total tau, glycogen synthase kinase-3beta (GSK-3beta), and phosphorylation of GSK-3beta Ser9 for observing the effect of IGF-1 or LiCl, a specific inhibitor of GSK-3beta, on Abeta-induced tau protein phosphorylation in PC12 cells.


RESULTS
Different concentrations of IGF-1 could improve the survival rate of PC12 cells compared with that of Abeta(1-40) group (P < 0.05), and the best protective effect was observed in 1 microg/mL IGF-1 group. The levels of tau protein phosphorylation in the sites of Ser396, Ser(199/202) and the amount of whole tau increased after 3 h exposure and reached the maximum level after 12 h exposure to Abeta(1-40), meanwhile, the expressions of the amount of whole GSK-3beta was also increased (P < 0.05), but a decreased phosphorylation of GSK-3betaSer9 was observed (P < 0.05). Pretreatment with several dose of IGF-1 or LiCl, markedly reduced Abeta(1-40)-induced tau hyperphosphorylation and the expression of GSK-3beta (P < 0.05), but the expression of phosphorylation of GSK-3betaSer9 was increased (P < 0.05).


CONCLUSIONS
The levels of tau protein phosphorylation in the sites of Ser396, Ser(199/202) and the amount of whole tau increased by Abeta(1-40) in PC12 cells, GSK-3beta activation by Abeta(1-40) may lead to extensive tau phosphorylation. IGF-1 could attenuate Abeta(1-40)-induced tau protein hyperphosphorylation by inhibiting the activation of GSK-3beta.
Department of Neurology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
Peng-jun
PJ
Wang
Yu
Y
Zhang
Rong-rong
RR
Song
Dong-fang
DF
Shen
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors*; D000818:Animals; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000037:antagonists & inhibitors*; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D016875:tau Proteins / Q000737:chemistry*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D020011:Protective Agents; C078592:amyloid beta-protein (1-40); D016875:tau Proteins; D007334:Insulin-Like Growth Factor I