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http://ntur.lib.ntu.edu.tw/handle/246246/94433
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| Title: | Hypoxia-Induced Inos Expression in Microglia Is Regulated by the P13- Kinase/Akt/Mtor Signaling Pathway and Activation of Hypoxia Inducible Factor-1 Alpha |
| Authors: | 盧大宇;湯智昕;符文美
LU, DAH-YUU;TANG, CHIH-HSIN;FU, WEN-MEI |
| Contributors: | 藥理學科所 |
| Keywords: | hypoxia;microglia;HIF-1 alpha;iNOS;Akt;Mtor |
| Date: | 2006 |
| Issue Date: | 2009-09-23T08:46:20Z |
| Abstract: | 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 underhypoxiahas not yet been defined. In the current work, we investigate the signaling pathways of HIF-1 alpha 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-1 alpha (HIF-1 alpha). 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-1 alpha in microglia. (c) 2006 Elsevier Inc. All rights reserved. |
| Relation: | BIOCHEMICAL PHARMACOLOGY v.72 n.8 pp.992-1000 |
| Appears in Collections: | [Dept. of Pharmacology and Graduate Institute of Pharmacology] Periodical Articles
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