Overactivated mitogen-activated protein kinase by anisomycin induces tau hyperphosphorylation / 生理学报
Acta Physiologica Sinica
;
(6): 485-491, 2008.
Artigo
em Inglês
| WPRIM
| ID: wpr-316701
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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Patologia
/
Farmacologia
/
Fosforilação
/
Emaranhados Neurofibrilares
/
Proteínas tau
/
Proteínas Quinases Dependentes de AMP Cíclico
/
Proteínas Quinases Ativadas por Mitógeno
/
Quinase 3 da Glicogênio Sintase
/
Linhagem Celular Tumoral
/
Doença de Alzheimer
Limite:
Animais
Idioma:
Inglês
Revista:
Acta Physiologica Sinica
Ano de publicação:
2008
Tipo de documento:
Artigo
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