PMID- 28489581
OWN - NLM
STAT- MEDLINE
DCOM- 20180425
LR  - 20211204
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 25
DP  - 2017 Jun 20
TI  - High glucose induces formation of tau hyperphosphorylation via Cav-1-mTOR 
      pathway: A potential molecular mechanism for diabetes-induced cognitive 
      dysfunction.
PG  - 40843-40856
LID - 10.18632/oncotarget.17257 [doi]
AB  - The abnormally hyperphosphorylated tau is thought to be implicated in 
      diabetes-associated cognitive deficits. The role of mammalian target of rapamycin 
      (mTOR) / S6 kinase (S6K) signalling in the formation of tau hyperphosphorylation 
      has been previously studied. Caveolin-1 (Cav-1), the essential structure protein 
      of caveolae, promotes neuronal survival and growth, and inhibits glucose 
      metabolism. In this study, we aimed to investigate the role of Cav-1 in the 
      formation of tau hyperphosphorylation under chronic hyperglycemic condition 
      (HGC). Diabetic rats were induced by streptozotocin (STZ). Primary hippocampal 
      neurons with or without molecular intervention such as the transient 
      over-expression or knock-down were subjected to HGC. The obtained experimental 
      samples were analyzed by real time quantitative RT-PCR, Western blot, 
      immunofluorescence or immunohistochemisty. We found: 1) that a chronic HGC 
      directly decreases Cav-1 expression, increases tau phosphorylation and activates 
      mTOR/S6K signalling in the brain neurons of diabetic rats, 2) that overexpression 
      of Cav-1 attenuates tau hyperphosphorylation induced by chronic HGC in primary 
      hippocampal neurons, whereas down-regulation of Cav-1 using Cav-1 siRNA 
      dramatically worsens tau hyperphosphorylation via mTOR/S6K signalling pathway, 
      and 3) that the down-regulation of Cav-1 induced by HGC is independent of mTOR 
      signalling. Our results suggest that tau hyperphosphorylation and the sustained 
      over-activated mTOR signalling under hyperglycemia may be due to the suppression 
      of Cav-1. Therefore, Cav-1 is a potential therapeutic target for diabetes-induced 
      cognitive dysfunction.
FAU - Wu, Jing
AU  - Wu J
AD  - Department of Endocrinology, Xiang-Ya Hospital, Central South University, 
      Changsha, China.
FAU - Zhou, Shan-Lei
AU  - Zhou SL
AD  - Department of Endocrinology, Xiang-Ya Hospital, Central South University, 
      Changsha, China.
FAU - Pi, Lin-Hua
AU  - Pi LH
AD  - Department of Endocrinology, Xiang-Ya Hospital, Central South University, 
      Changsha, China.
FAU - Shi, Xia-Jie
AU  - Shi XJ
AD  - Department of Endocrinology, Xiang-Ya Hospital, Central South University, 
      Changsha, China.
FAU - Ma, Ling-Ran
AU  - Ma LR
AD  - Department of Pharmaceutical Engineering, College of Chemistry and Chemical 
      Engineering, Central South University, Changsha, China.
FAU - Chen, Zi
AU  - Chen Z
AD  - Department of Endocrinology, Xiang-Ya Hospital, Central South University, 
      Changsha, China.
FAU - Qu, Min-Li
AU  - Qu ML
AD  - Department of Endocrinology, Xiang-Ya Hospital, Central South University, 
      Changsha, China.
FAU - Li, Xin
AU  - Li X
AD  - Department of Pharmaceutical Engineering, College of Chemistry and Chemical 
      Engineering, Central South University, Changsha, China.
FAU - Nie, Sheng-Dan
AU  - Nie SD
AD  - Institute of Clinical Medicine, People's Hospital of Hunan province, The First 
      Affiliated Hospital of Hunan Normal University, Changsha, China.
FAU - Liao, Duan-Fang
AU  - Liao DF
AD  - Division of Stem Cell Regulation and Application, School of Pharmacy, Hunan 
      University of Traditional Chinese Medicine, Changsha, Hunan, China.
FAU - Pei, Jin-Jing
AU  - Pei JJ
AD  - KI-Alzheimer's Disease Research Center, Karolinska Institutet, Novum, Stockholm, 
      Sweden.
AD  - Department of Neurology, Xuan Wu Hospital, Capital Medical University, China.
AD  - Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, 
      China.
FAU - Wang, Shan
AU  - Wang S
AD  - Department of Endocrinology, Xiang-Ya Hospital, Central South University, 
      Changsha, China.
AD  - Department of Pharmaceutical Engineering, College of Chemistry and Chemical 
      Engineering, Central South University, Changsha, China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Cav1 protein, rat)
RN  - 0 (Caveolin 1)
RN  - 0 (tau Proteins)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Caveolin 1/*metabolism
MH  - Cognitive Dysfunction/*metabolism
MH  - Diabetes Mellitus, Experimental/*metabolism/*psychology
MH  - Glucose/administration & dosage/metabolism
MH  - Hyperglycemia/metabolism/psychology
MH  - Male
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Transfection
MH  - tau Proteins/*metabolism
PMC - PMC5522306
OTO - NOTNLM
OT  - caveolin-1
OT  - cognitive dysfunction
OT  - diabetes mellitus
OT  - mTOR
OT  - tau hyperphosphorylation
COIS- CONFLICTS OF INTEREST The authors declare no conflicts of interest.
EDAT- 2017/05/11 06:00
MHDA- 2018/04/26 06:00
PMCR- 2017/06/20
CRDT- 2017/05/11 06:00
PHST- 2017/02/20 00:00 [received]
PHST- 2017/04/07 00:00 [accepted]
PHST- 2017/05/11 06:00 [pubmed]
PHST- 2018/04/26 06:00 [medline]
PHST- 2017/05/11 06:00 [entrez]
PHST- 2017/06/20 00:00 [pmc-release]
AID - 17257 [pii]
AID - 10.18632/oncotarget.17257 [doi]
PST - ppublish
SO  - Oncotarget. 2017 Jun 20;8(25):40843-40856. doi: 10.18632/oncotarget.17257.