The effect of 0, 30, 60, 120, 240, 360 min hypoxia on the release of NO and PGE2 was investigated in human cultured astroglial cells. Exposure of astroglial cells to hypoxic injury produced a dose-dependent increase of the nitrite (the breakdown product of NO) level in the cell supernatant. In addition, a significant activation of the inducible isoform of NO synthase was seen, demonstrating that the enhancement on NO release produced by hypoxic injury was related to an increased biosynthesis of NO-generating enzyme(s). This effect was strongly antagonised by pretreating cells with dexamethasone (20 μM). The increase in NO release by hypoxic astroglial cells was accompanied by sustained release of PGE2, which was antagonised by the cycloxygenase inhibitor indomethacin (10 μM), and partially attenuated by L-NAME (100 μM), a nitric oxide synthase inhibitor, showing that the release of PGE2 was driven by NO. Finally, inducible NOS activity elicited by hypoxic injury, was antagonised by incubating astroglial cells with antibodies directed against type2 receptor for IL1β. In conclusion, hypoxia stimulates cytokine network in astroglial cells leading to enhanced release of NO and prostanoids and this may represent a key mechanism in cerebral blood flow disturbances.
|Number of pages||4|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - Sep 29 1997|
ASJC Scopus subject areas
- Molecular Biology