PMID- 16919605
OWN - NLM
STAT- MEDLINE
DCOM- 20061108
LR  - 20220316
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 72
IP  - 8
DP  - 2006 Oct 16
TI  - Hypoxia-induced iNOS expression in microglia is regulated by the 
      PI3-kinase/Akt/mTOR signaling pathway and activation of hypoxia inducible 
      factor-1alpha.
PG  - 992-1000
AB  - Exposure to hypoxia induced microglia activation and animal studies have shown 
      that neuronal cell death is correlated with microglial activation following 
      cerebral ischemia. Thus, it is likely that toxic inflammatory mediators produced 
      by activated microglia under hypoxic conditions may exacerbate neuronal injury 
      following cerebral ischemia. The hypoxia-inducible factor-1 (HIF-1) is primarily 
      involved in the sensing and adapting of cells to changes in the O(2) level, which 
      is regulated by many physiological functions. However, the role of HIF-1 in 
      microglia activation under hypoxia has not yet been defined. In the current work, 
      we investigate the signaling pathways of HIF-1alpha involved in the regulation of 
      hypoxia-induced overexpression of inducible NO synthase (iNOS) in microglia. 
      Exposure of primary rat microglial cultures as well as established microglial 
      cell line BV-2 to hypoxia induced the expression of iNOS, indicating that hypoxia 
      could lead to the inflammatory activation of microglia. iNOS induction was 
      accompanied with NO production. Moreover, the molecular analysis of these events 
      indicated that iNOS expression was regulated by the phosphatidylinositol 3-kinase 
      (PI3-kinase)/AKT/ mammalian target of rapamycin (mTOR) signaling pathway and 
      activation of hypoxia inducible factor-1alpha (HIF-1alpha). Thus, during cerebral 
      ischemia, hypoxia may not only directly damage neurons, but also promote neuronal 
      injury indirectly via microglia activation. In this study, we demonstrated that 
      hypoxia induced iNOS expression by regulation of HIF-1alpha in microglia.
FAU - Lu, Dah-Yuu
AU  - Lu DY
AD  - Pharmacological Institute, College of Medicine, National Taiwan University, 
      Taipei, Taiwan.
FAU - Liou, Houng-Chi
AU  - Liou HC
FAU - Tang, Chih-Hsin
AU  - Tang CH
FAU - Fu, Wen-Mei
AU  - Fu WM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060817
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - EC 1.14.13.39 (Nos2 protein, rat)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Cell Hypoxia/*physiology
MH  - Cell Line
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Mice
MH  - Microglia/*metabolism
MH  - Nitric Oxide/biosynthesis
MH  - Nitric Oxide Synthase Type II/*metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Protein Kinases/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases
EDAT- 2006/08/22 09:00
MHDA- 2006/11/10 09:00
CRDT- 2006/08/22 09:00
PHST- 2006/05/17 00:00 [received]
PHST- 2006/06/25 00:00 [revised]
PHST- 2006/06/28 00:00 [accepted]
PHST- 2006/08/22 09:00 [pubmed]
PHST- 2006/11/10 09:00 [medline]
PHST- 2006/08/22 09:00 [entrez]
AID - S0006-2952(06)00397-2 [pii]
AID - 10.1016/j.bcp.2006.06.038 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2006 Oct 16;72(8):992-1000. doi: 10.1016/j.bcp.2006.06.038. 
      Epub 2006 Aug 17.