Linked Life Data

16919605

Source:http://linkedlifedata.com/resource/pubmed/id/16919605

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2006-9-19
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha..., http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide, http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II, http://linkedlifedata.com/resource/pubmed/chemical/Nos2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Nos2 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt, http://linkedlifedata.com/resource/pubmed/chemical/TOR Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/mTOR protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/mTOR protein, rat
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
72
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
992-1000
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Hypoxia-induced iNOS expression in microglia is regulated by the PI3-kinase/Akt/mTOR signaling pathway and activation of hypoxia inducible factor-1alpha.
pubmed:affiliation
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't