PMID- 17203200
OWN - NLM
STAT- MEDLINE
DCOM- 20070313
LR  - 20211203
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 19
IP  - 2
DP  - 2007 Feb
TI  - The pro-survival pathways of mTOR and protein kinase B target glycogen synthase 
      kinase-3beta and nuclear factor-kappaB to foster endogenous microglial cell 
      protection.
PG  - 263-72
AB  - Microglia of the central nervous system serve a variety of functions that may 
      ultimately lead to the development or detriment of neighboring neuronal and 
      vascular cells. These scavengers of the nervous system have been associated with 
      a variety of neurodegenerative disorders, but the toxic potential of microglia is 
      equally balanced by the protective nature of these cells to exclude foreign 
      microorganisms and promote new tissue proliferation and reorganization. To this 
      extent, our work outlines a series of endogenous microglial cellular pathways 
      that can constitute protection for microglia against during oxygen-glucose 
      deprivation (OGD). We demonstrate in both primary microglia and the microglial 
      cell line EOC 2 that endogenous microglial protection against OGD relies upon the 
      activation and expression of the phosphatidylinositol 3-kinase pathways of 
      mammalian target of rapamycin (mTOR) and protein kinase B (Akt1), since 
      pharmacological inhibition of mTOR or Akt1 as well as the gene silencing of Akt1 
      protein expression leads to significantly increased microglial apoptotic cell 
      injury, DNA fragmentation, and membrane phosphatidylserine exposure. The mTOR 
      pathway may offer endogenous protection through mechanisms that do not entirely 
      rely upon inhibition of glycogen synthase kinase-3beta (GSK-3beta) activity while 
      Akt1 appears to converge upon the necessary blockade of GSK-3beta. Closely 
      aligned to these endogenous protective mechanisms is the subcellular presence and 
      nuclear translocation of nuclear factor-kappaB p65 (NF-kappaB p65), since 
      microglial cell injury is significantly increased during the gene silencing of 
      NF-kappaB p65. Elucidating the underlying pathways that can afford endogenous 
      protection and maintain functional integrity of microglia should offer new 
      prospects for the treatment of a broad range of nervous system disorders.
FAU - Chong, Zhao Zhong
AU  - Chong ZZ
AD  - Division of Cellular and Molecular Cerebral Ischemia, Wayne State University 
      School of Medicine, 4201 St. Antoine, Detroit, MI 48201, USA.
FAU - Li, Faqi
AU  - Li F
FAU - Maiese, Kenneth
AU  - Maiese K
LA  - eng
GR  - P30 ES006639/ES/NIEHS NIH HHS/United States
GR  - R01 NS053946/NS/NINDS NIH HHS/United States
GR  - R01 NS053946-01A2/NS/NINDS NIH HHS/United States
GR  - P30 ES 06639/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (NF-kappa B)
RN  - 0 (Phosphatidylserines)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Protein Subunits)
RN  - 0 (RNA, Small Interfering)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, rat)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - IY9XDZ35W2 (Glucose)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Cell Membrane/chemistry
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Cytoprotection
MH  - Cytosol/drug effects/metabolism
MH  - DNA Fragmentation/drug effects
MH  - Enzyme Activation
MH  - Glucose/pharmacology
MH  - Glycogen Synthase Kinase 3/antagonists & inhibitors/*metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - NF-kappa B/genetics/*metabolism
MH  - Neuroglia/*cytology/drug effects/*metabolism
MH  - Oxygen/pharmacology
MH  - Phosphatidylserines/chemistry/pharmacology
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Protein Kinases/*metabolism
MH  - Protein Subunits/metabolism
MH  - Protein Transport
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - RNA, Small Interfering/genetics
MH  - Rats
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases
PMC - PMC1986680
MID - NIHMS29318
EDAT- 2007/01/05 09:00
MHDA- 2007/03/14 09:00
PMCR- 2007/09/19
CRDT- 2007/01/05 09:00
PHST- 2007/01/05 09:00 [pubmed]
PHST- 2007/03/14 09:00 [medline]
PHST- 2007/01/05 09:00 [entrez]
PHST- 2007/09/19 00:00 [pmc-release]
PST - ppublish
SO  - Int J Mol Med. 2007 Feb;19(2):263-72.