Overactivated mitogen-activated protein kinase by anisomycin induces tau hyperphosphorylation.
- Author:
Qun WANG
1
;
Jia-Yu ZHANG
;
Shi-Jie LIU
;
Hong-Lian LI
Author Information
1. Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
- Publication Type:Journal Article
- MeSH:
Alzheimer Disease;
pathology;
Animals;
Anisomycin;
pharmacology;
Cell Line, Tumor;
Cyclic AMP-Dependent Protein Kinases;
metabolism;
Glycogen Synthase Kinase 3;
metabolism;
Mice;
Mitogen-Activated Protein Kinases;
metabolism;
Neurofibrillary Tangles;
pathology;
Phosphorylation;
tau Proteins;
metabolism
- From:
Acta Physiologica Sinica
2008;60(4):485-491
- CountryChina
- Language:English
-
Abstract:
One of the pathological feathers of Alzheimer's disease (AD) is neurofibrillary tangles (NFTs), which consist of paired helical filaments (PHFs) formed by hyperphosphorylated microtubule-associated protein tau. To study the role of mitogen-activated protein kinase (MAPK) in tau hyperphosphorylation and the underlying mechanism, wild type mouse neuroblastoma cells (N2a) were dealt with different concentrations (0.1 microg/mL, 0.2 microg/mL and 0.4 microg/mL) of anisomycin (an activator of MAPK) for 6 h. The relationship between MAPK activity and tau phosphorylation at some Alzheimer-sites was analyzed, and the activities of protein kinase A (PKA) and glycogen synthase kinase-3 (GSK-3) were detected. The results showed that anisomycin activated MAPK in a dose-dependent manner, but tau hyperphosphorylation at Ser-198/199/202 and Ser-396/404 sites was only observed when the concentration of anisomycin was at the level of 0.4 microg/mL, and the alteration of tau phosphorylation at Ser-214 showed no significant difference in different groups. 0.2 microg/mL and 0.4 microg/mL of anisomycin led to an increase in the activity of GSK-3, respectively, but had no effect on the activity of PKA. Lithium chloride, a specific inhibitor of GSK-3, completely abolished the anisomycin-induced elevation of tau phosphorylation without any effect on the activity of MAPK. In conclusion, overactivation of MAPK up to a certain degree induces tau hyperphosphorylation at Ser-198/199/202 and Ser-396/404 sites, and this is probably related to the effect of activated GSK-3 by MAPK.
