Influence Of α7 Nicotinic Acetylcholine Receptor Antagonized Or Gene Silence On P-Tau(S404)and P-Tau(S214) Phosphorylation And The Relationship With P38 MAPK Signal Transduction Pathway In SH-SY5Y Cells

Objective: To investigate the influence of α7 neuronal nicotinic acetylcholine receptor(nAChR)antagonized or gene silence on p-Tau(S404)and p-Tau(S214)sites phosphorylation and the relationship with p38 MAPK signal transduction pathway in SH-SY5 Y cells,to study the effected mechanism of α7nAChR on Tau sites phosphorylation.Methods: SH-SY5 Y cells were respectively or combined exposed to MLA,an antagonist of α7 nAChR,Anisomycin,a agonist of p38 MAPK pathway,and SB203580,a blocker of p38 MAPK pathway.The level ofα7 nAChR mRNA and protein were detected by real-time PCR and western blotting,respectively.The protein levels of Tau,p-Tau(S404),p-Tau(S214),p38 MAPK and p-p38 MAPK(Thr180/Tyr182)were measured by Western blotting.Results: As compared with negative controls,the expression of α7 nAChR at mRNA and protein levels in the SH-SY5 Y cells with α7 nAChR silencing were decreased by 91% and80%,respectively.And the expression of p-Tau(S404),p-Tau(S214),and P-p38MAPK(Thr180/Tyr182)proteins were increased by 71%,73%,65%,respectively.Besides,compared with the blank group,in MLA treated group and in Anisomycin add MLA group,the expressions of p-Tau(S404),p-Tau(S214)and p-p38 MAPK were both increased significantly.In SB203580 add MLA group,the expressions of p-Tau(S404),p-Tau(S214)and p-p38 MAPK were decreased conspicuously.Conlusions: The gene silence or receptor antagonized of α7 nAChR can both lead to p-Tau(S404)and p-Tau(S214)hyperphosphorylation and activate p38 MAPK pathway.Inhibited p38 MAPK signal transduction pathway can prevent against the MLA-induced p-Tau(S404)and p-Tau(S214)hyperphosphorylation.