PMID- 21854819
OWN - NLM
STAT- MEDLINE
DCOM- 20130129
LR  - 20211203
IS  - 1872-9754 (Electronic)
IS  - 0197-0186 (Linking)
VI  - 59
IP  - 6
DP  - 2011 Nov
TI  - Insulin-induced neurite-like process outgrowth: acceleration of tau protein 
      synthesis via a phosphoinositide 3-kinase~mammalian target of rapamycin pathway.
PG  - 880-8
LID - 10.1016/j.neuint.2011.08.002 [doi]
AB  - Both insulin and tau, promoting neuronal differentiation (neurite outgrowth, 
      neuronal polarity, and myelination) and cell survival, are associated with 
      neurodegenerative disease (e.g., Alzheimer's disease). The aim of this study was 
      to explore relation between insulin-induced activation of insulin signal and 
      expression of tau protein on neurite-like process outgrowth in adrenal chromaffin 
      cells. Primary cultured bovine adrenal chromaffin cells were incubated with 
      insulin to determine whether stimulant of insulin signal could affect tau 
      expression and neurite-like process outgrowth. Chronic treatment with insulin 
      (⩾6h) led neurite-like process outgrowth as well as increased tau protein level 
      by  approximately 99% in a concentration (EC(50) 5.5nM)- and time-dependent manner, without 
      changing Ser(396)-phosphorylated tau level. The insulin-induced increase of tau 
      protein level was abolished by LY294002 [an inhibitor of phosphoinositide 
      3-kinase (PI3K)] and rapamycin [an inhibitor of mammalian target of rapamycin 
      (mTOR)], but not by PD98059 and U0126 [two inhibitors of mitogen-activated 
      protein kinase/extracellular signal-regulated kinase (MEK)]. Additionally, 
      insulin-induced increase of tau was blocked by cyclohexamide (an inhibitor of 
      protein synthesis), but not by actinomycin D (an inhibitor of gene 
      transcription). Pulse-label followed by polyacrylamide gel electrophoresis 
      revealed that insulin accelerated tau protein synthesis rate (t(1/2)) from 2.6 to 
      1.9h. Insulin did not change tau mRNA level. Taken together, these results 
      suggest that insulin-induced activation of PI3K approximately mTOR pathway up-regulated tau 
      protein via acceleration of protein synthesis, on which insulin promoted 
      neurite-like process outgrowth.
CI  - Copyright A(c) 2011 Elsevier B.V. All rights reserved.
FAU - Nemoto, Takayuki
AU  - Nemoto T
AD  - Department of Pharmacology, Miyazaki Medical College, University of Miyazaki, 
      Miyazaki, Japan. tnemoto@fc.miyazaki-u.ac.jp
FAU - Yanagita, Toshihiko
AU  - Yanagita T
FAU - Satoh, Shinya
AU  - Satoh S
FAU - Maruta, Toyoaki
AU  - Maruta T
FAU - Kanai, Tasuku
AU  - Kanai T
FAU - Murakami, Manabu
AU  - Murakami M
FAU - Wada, Akihiko
AU  - Wada A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110809
PL  - England
TA  - Neurochem Int
JT  - Neurochemistry international
JID - 8006959
RN  - 0 (Insulin)
RN  - 0 (tau Proteins)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - *Cell Enlargement/drug effects
MH  - Insulin/*pharmacology
MH  - Neural Pathways/drug effects/enzymology/physiology
MH  - Neurites/drug effects/enzymology/*physiology
MH  - Neurogenesis/drug effects/*physiology
MH  - Phosphatidylinositol 3-Kinases/*physiology
MH  - Primary Cell Culture
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/genetics/*physiology
MH  - Up-Regulation/drug effects/*physiology
MH  - tau Proteins/*biosynthesis/metabolism
EDAT- 2011/08/23 06:00
MHDA- 2013/01/30 06:00
CRDT- 2011/08/23 06:00
PHST- 2011/04/15 00:00 [received]
PHST- 2011/07/28 00:00 [revised]
PHST- 2011/08/01 00:00 [accepted]
PHST- 2011/08/23 06:00 [entrez]
PHST- 2011/08/23 06:00 [pubmed]
PHST- 2013/01/30 06:00 [medline]
AID - S0197-0186(11)00272-5 [pii]
AID - 10.1016/j.neuint.2011.08.002 [doi]
PST - ppublish
SO  - Neurochem Int. 2011 Nov;59(6):880-8. doi: 10.1016/j.neuint.2011.08.002. Epub 2011 
      Aug 9.