PMID- 27924507
OWN - NLM
STAT- MEDLINE
DCOM- 20170505
LR  - 20181113
IS  - 1993-1352 (Electronic)
IS  - 1672-0733 (Linking)
VI  - 36
IP  - 6
DP  - 2016 Dec
TI  - TPPU protects tau from H(2)O(2)-induced hyperphosphorylation in HEK293/tau cells 
      by regulating PI3K/AKT/GSK-3beta pathway.
PG  - 785-790
LID - 10.1007/s11596-016-1662-z [doi]
AB  - Neurofibrillary pathology of abnormally hyperphosphorylated tau is a hallmark of 
      Alzheimer's disease (AD) and other tauopathies. Phosphatidylinositol 3-kinase 
      (PI3K)/Akt/glycogen synthase kinase-3 beta (GSK-3beta) signaling pathway is pivotal 
      for tau phosphorylation. Inhibition of soluble epoxide hydrolase (sEH) metabolism 
      has been shown to effectively increase the accumulation of epoxyeicosatrienoic 
      acids (EETs), which are cytochrome P450 metabolites of arachidonic acid and have 
      been demonstrated to have neuroprotective effects. However, little is known about 
      the role of sEH in tau phosphorylation. The present study investigated the role 
      of a sEH inhibitor, 1-(1-propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl] 
      urea (TPPU), on H(2)O(2)-induced tau phosphorylation and the underlying signaling 
      pathway in human embryonic kidney 293 (HEK293)/Tau cells. We found that the cell 
      viability was increased after TPPU treatment compared to control in oxidative 
      stress. Western blotting and immunofluorescence results showed that the levels of 
      phosphorylated tau at Thr231 and Ser396 sites were increased in H(2)O(2)-treated 
      cells but dropped to normal levels after TPPU administration. H(2)O(2) induced an 
      obvious decreased phosphorylation of GSK-3beta at Ser9, an inactive form of GSK-3beta, 
      while there were no changes of phosphorylation of GSK-3beta at Tyr216. TPPU 
      pretreatment maintained GSK-3beta Ser 9 phosphorylation. Moreover, Western blotting 
      results showed that TPPU upregulated the expression of p-Akt. The protective 
      effects of TPPU were found to be inhibited by wortmannin (WT, a specific PI3K 
      inhibitor). In conclusion, these results suggested that the protective effect of 
      TPPU on H(2)O(2)-induced oxidative stress is associated with PI3K/Akt/GSK-3beta 
      pathway.
FAU - Yao, En-Sheng
AU  - Yao ES
AD  - Department of Neurology, Tongji Hospital, Tongji Medicine College, Huazhong 
      University of Science and Technology, Wuhan, 430030, China.
AD  - Department of Neurology, Shihezi University, Shihezi, 832008, China.
FAU - Tang, Yan
AU  - Tang Y
AD  - Department of Geriatrics, The First Affiliated Hospital, School of Medicine, 
      Shihezi University, Shihezi, 832008, China.
FAU - Liu, Xing-Hua
AU  - Liu XH
AD  - Department of Neurology, Tongji Hospital, Tongji Medicine College, Huazhong 
      University of Science and Technology, Wuhan, 430030, China. liu_xingh@126.com.
FAU - Wang, Ming-Huan
AU  - Wang MH
AD  - Department of Neurology, Tongji Hospital, Tongji Medicine College, Huazhong 
      University of Science and Technology, Wuhan, 430030, China.
LA  - eng
PT  - Journal Article
DEP - 20161207
PL  - China
TA  - J Huazhong Univ Sci Technolog Med Sci
JT  - Journal of Huazhong University of Science and Technology. Medical sciences = Hua 
      zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. 
      Yixue Yingdewen ban
JID - 101169627
RN  - 0 (1-trifluoromethoxyphenyl-3-(1-propionylpiperidine-4-yl)urea)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Piperidines)
RN  - 0 (tau Proteins)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Cell Survival/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Glycogen Synthase Kinase 3 beta/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Hydrogen Peroxide/toxicity
MH  - Oxidative Stress
MH  - Phenylurea Compounds/*pharmacology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation
MH  - Piperidines/*pharmacology
MH  - *Protein Processing, Post-Translational
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - *Signal Transduction
MH  - tau Proteins/*metabolism
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - GSK-3beta
OT  - TPPU
OT  - tau
EDAT- 2016/12/08 06:00
MHDA- 2017/05/06 06:00
CRDT- 2016/12/08 06:00
PHST- 2016/06/16 00:00 [received]
PHST- 2016/09/17 00:00 [revised]
PHST- 2016/12/08 06:00 [entrez]
PHST- 2016/12/08 06:00 [pubmed]
PHST- 2017/05/06 06:00 [medline]
AID - 10.1007/s11596-016-1662-z [pii]
AID - 10.1007/s11596-016-1662-z [doi]
PST - ppublish
SO  - J Huazhong Univ Sci Technolog Med Sci. 2016 Dec;36(6):785-790. doi: 
      10.1007/s11596-016-1662-z. Epub 2016 Dec 7.