PMID- 22460328
OWN - NLM
STAT- MEDLINE
DCOM- 20120817
LR  - 20161125
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 29
IP  - 4
DP  - 2012
TI  - Bip enhanced the association of GSK-3beta with tau during ER stress both in vivo and 
      in vitro.
PG  - 727-40
LID - 10.3233/JAD-2012-111898 [doi]
AB  - Hyperphosphorylated tau is the major component of intracellular neurofibrillary 
      tangles, which is positively correlated with the cognitive decline in Alzheimer's 
      disease (AD). The upstream factors leading to tau hyperphosphorylation are still 
      not fully understood. Endoplasmic reticulum (ER) stress has been indicated in AD 
      pathogenesis and the increased level of binding immunoglobulin protein (Bip), an 
      important ER associated chaperon, is increased in AD brain. Here 
      hyperphosphorylation of tau, activation of glycogen synthase kinase-3beta (GSK-3beta), 
      and elevation of Bip were induced by ventricular infusion of ER stressors, 
      tunicamycin (TM) and thapsigargin (TG), in rats. GSK-3beta was found to be 
      responsible for tau hyperphosphorylation induced by ER stressors both in vivo and 
      in vitro. In addition, inhibited Akt, protein tyrosine phosphatase 1B, and 
      activated Fyn were detected in vivo. Down-regulating Bip by tranfecting its siRNA 
      plasmid significantly revised tau hyperphosphorylation in TG treated HEK293/tau 
      cells, but the activation of GSK-3beta was still observed. By immunoprecipitation, 
      we found that the binding levels of Bip to tau and GSK-3beta were significantly 
      increased with the elevation of Bip in TM-treated rats. Moreover, in Bip 
      overexpressed HEK293/tau cells, the binding levels of Bip to tau (mainly 
      phosphorylated tau) and GSK-3beta were also significantly increased. However, 
      beta-catenin, another important substrate of GSK-3beta, was not found bound to the 
      increased Bip. All these data suggest an essential role of Bip in GSK-3beta 
      dependent tau hyperphosphorylation in ER stress by promoting the binding of 
      GSK-3beta to tau.
FAU - Liu, Zan-Chao
AU  - Liu ZC
AD  - Department of Pathology and Pathophysiology, Key Laboratory of Neurological 
      Disease of National Education Ministry and Hubei Province, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan, China.
FAU - Fu, Zheng-Qi
AU  - Fu ZQ
FAU - Song, Jie
AU  - Song J
FAU - Zhang, Jia-Yu
AU  - Zhang JY
FAU - Wei, Yu-Ping
AU  - Wei YP
FAU - Chu, Jiang
AU  - Chu J
FAU - Han, Li
AU  - Han L
FAU - Qu, Na
AU  - Qu N
FAU - Wang, Jian-Zhi
AU  - Wang JZ
FAU - Tian, Qing
AU  - Tian Q
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Lymphokines)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (enhanced green fluorescent protein)
RN  - 0 (immunoglobulin-binding factors)
RN  - 0 (tau Proteins)
RN  - 11089-65-9 (Tunicamycin)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 2.7.11.1 (GSK3B protein, human)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, rat)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - EC 3.1.3.16 (Ppp2ca protein, rat)
RN  - EC 3.1.3.16 (Protein Phosphatase 2)
SB  - IM
MH  - Animals
MH  - Cell Line, Transformed
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation/drug effects/*physiology
MH  - Endoplasmic Reticulum Stress/drug effects/*physiology
MH  - Enzyme Activation/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Glycogen Synthase Kinase 3/*metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Green Fluorescent Proteins/genetics
MH  - Humans
MH  - Immunoprecipitation
MH  - Injections, Intraventricular
MH  - Lymphokines/genetics/*metabolism
MH  - Male
MH  - Mutation/genetics
MH  - Phosphorylation/drug effects
MH  - Protein Phosphatase 2/metabolism
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Thapsigargin/pharmacology
MH  - Time Factors
MH  - Transfection
MH  - Tunicamycin/pharmacology
MH  - tau Proteins/*metabolism
EDAT- 2012/03/31 06:00
MHDA- 2012/08/18 06:00
CRDT- 2012/03/31 06:00
PHST- 2012/03/31 06:00 [entrez]
PHST- 2012/03/31 06:00 [pubmed]
PHST- 2012/08/18 06:00 [medline]
AID - D5X772412RJ480G1 [pii]
AID - 10.3233/JAD-2012-111898 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2012;29(4):727-40. doi: 10.3233/JAD-2012-111898.