Endoplasmic reticulum stress is involved in okadaic acid-induced tau phosphorylation and neurotoxic

The role of the endoplasmic reticulum in Alzheimer's disease pathogenesis remains poody understood.The present study investigated the correlation of okadaic acid-induced tau hyperphosphorylation and neurotoxicity with endoplasmic reticulum stress.Following co-culture of various concentrations of okadaic acid (25,50,100,and 200 nmol/L) and human neuroblastoma SH-SY5Y cells,okadaic acid,a selective protein phosphatase (PP-1,PP-2A) inhibitor,reduced cell viability in a concentration-dependent manner,which was closely associated with okadaic acid-induced tau phosphorylation.In addition,expressions of the unfolded protein response activation marker glucose-regulated protein 78 (BiP/Grp78) and the CCAAT/enhancer binding protein homologous protein (CHOP)/Gadd153 increased following okadaic acid treatment.Furthermore,the unfolded protein response was activated in human embryonic kidney 293 (HEK 293) cells overexpressing tau following okadaic acid treatment,but untransfected HEK 293 cells did not exhibit activation of the unfolded protein response.These data indicate that endoplasmic reticulum stress is involved in mechanisms underlying tau phosphorylation and the cytotoxic effects of okadaic acid.