PMID- 22802092
OWN - NLM
STAT- MEDLINE
DCOM- 20131112
LR  - 20120903
IS  - 1573-675X (Electronic)
IS  - 1360-8185 (Linking)
VI  - 17
IP  - 10
DP  - 2012 Oct
TI  - Expression of the hyperphosphorylated tau attenuates ER stress-induced apoptosis 
      with upregulation of unfolded protein response.
PG  - 1039-49
LID - 10.1007/s10495-012-0744-z [doi]
AB  - The neural dysfunction in Alzheimer's disease (AD) could arise from endoplasmic 
      reticulum (ER) stress and deficits of the unfolded protein response (UPR). To 
      explore whether tau hyperphosphorylation, a hallmark of AD brain pathologies, 
      plays a role in ER stress-induced alterations of cell viability, we established 
      cell lines with stable expression of human tau (HEK293/tau) or the vector 
      (HEK293/vec) and treated the cells with thapsigargin (TG), an ER stress inducer. 
      We observed that the HEK293/tau cells were more resistant than the HEK293/vec 
      cells to the TG-induced apoptosis, importantly, a time dependent increase of tau 
      phosphorylation at Thr205 and Thr231 sites was positively correlated with the 
      inhibition of apoptosis. We also observed that expression of tau upregulated 
      phosphorylation of PERK, eIF2 and IRE1 with an increased cleavage of ATF6 and 
      ATF4. The potentiation of UPR was also detected in HEK293/tau cells treated with 
      other ER stress inducers, including staurosporine, camptothecin and hydrogen 
      peroxide, in which a suppressed apoptosis was also shown. Our data suggest that 
      tau hyperphosphorylation could attenuate the ER stress-induced apoptosis with the 
      mechanism involving upregulation of UPR system.
FAU - Liu, Xin-An
AU  - Liu XA
AD  - Pathophysiology Department, Key Laboratory of Neurological Disease of National 
      Education Ministry and Hubei Province, Tongji Medical College, Huazhong 
      University of Science and Technology, 430030 Wuhan, China. xinanliu@scripps.edu
FAU - Song, Jie
AU  - Song J
FAU - Jiang, Qian
AU  - Jiang Q
FAU - Wang, Qun
AU  - Wang Q
FAU - Tian, Qing
AU  - Tian Q
FAU - Wang, Jian-Zhi
AU  - Wang JZ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Apoptosis
JT  - Apoptosis : an international journal on programmed cell death
JID - 9712129
RN  - 0 (tau Proteins)
RN  - 67526-95-8 (Thapsigargin)
SB  - IM
MH  - Alzheimer Disease/pathology
MH  - Apoptosis/*drug effects
MH  - Endoplasmic Reticulum Stress/drug effects/*physiology
MH  - HEK293 Cells
MH  - Humans
MH  - Phosphorylation
MH  - Thapsigargin/pharmacology
MH  - Unfolded Protein Response/*drug effects
MH  - tau Proteins/*metabolism
EDAT- 2012/07/18 06:00
MHDA- 2013/11/13 06:00
CRDT- 2012/07/18 06:00
PHST- 2012/07/18 06:00 [entrez]
PHST- 2012/07/18 06:00 [pubmed]
PHST- 2013/11/13 06:00 [medline]
AID - 10.1007/s10495-012-0744-z [doi]
PST - ppublish
SO  - Apoptosis. 2012 Oct;17(10):1039-49. doi: 10.1007/s10495-012-0744-z.