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P2‐162: Over‐induced apoptosis expression of tau protects cells from ER stress
Author(s) -
Liu Xinan,
Tian Qing,
Wang Jianzhi
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.474
Subject(s) - unfolded protein response , thapsigargin , apoptosis , endoplasmic reticulum , atf6 , microbiology and biotechnology , tunicamycin , hek 293 cells , tau protein , signal transduction , phosphorylation , biology , chemistry , cell culture , medicine , biochemistry , alzheimer's disease , genetics , disease
Background: Abnormal hyperphosphorylated tau plays significant role in the pathological development of Alzheimer’s disease (AD). Endoplasmic reticulum (ER) stress, an important upstream link of apoptosis, has been indicated involved in the pathological process of AD. However, the role of tau in ER stress-induced apoptosis is still unknown. Methods: The longest human tau (tau441) cDNA was stably transfected into HEK293 cells (HEK293/tau). Cell Death Detection ELISA was used to detect cell apoptosis. Western blot was used to evaluate the total level and phosphorylation level of tau and the ER stress signal system. Results: Apoptosis rates were markedly and rapidly induced in HEK293 cells at 3h, 6h, 12h, 24h and 48h after treatment of ER stress inducers, thapsigargin (1 mM) or tunicamycin (5 mg/ml). In HEK293/tau cells, apoptosis rate were reduced nearly 50% at different time points. Tau phosphorylation levels were concomitantly increased at Ser. It was also found that during thapsigargininduced ER stress, three transmembrane proteins which sense the ER stress, IRE1, ATF6 and PERK, as well as the downstream adaptive pathway signaling molecules, eIF2a, XBP-1 were significantly activated. Conclusions: Tau protein protects cells from ER stress-induced apoptosis, while potentiating adaptive mechanisms via enhancement of the ER stress signal system might be the major factor in the protection of tau from ER stress-induced apoptosis.