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Neuroprotective MK801 is associated with nitric oxide synthase during hypoxia/reoxygenation in rat cortical cell cultures
Author(s) -
Huang HsuehMeei,
Shen ChiungChyi,
Ou HsiuChung,
Yu JeanYuan,
Chen HuanLian,
Kuo JonSon,
Hsieh ShonJean
Publication year - 2001
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10022
Subject(s) - neuroprotection , nitric oxide , hypoxia (environmental) , nitric oxide synthase , lactate dehydrogenase , chemistry , pharmacology , nmda receptor , endocrinology , medicine , biology , biochemistry , receptor , oxygen , enzyme , organic chemistry
The neuroprotective effect of MK801 against hypoxia and/or reoxygenation‐induced neuronal cell injury and its relationship to neuronal nitric oxide synthetase (nNOS) expression were examined in cultured rat cortical cells. Treatment of cortical neuronal cells with hypoxia (95% N 2 /5% CO 2 ) for 2 h followed by reoxygenation for 24 h induced a release of lactate dehydrogenase (LDH) into the medium, and reduced the protein level of MAP‐2 as well. MK801 attenuated the release of LDH and the reduction of the MAP‐2 protein by hypoxia, suggesting a neuroprotective role of MK801. MK801 also diminished the number of nuclear condensation by hypoxia/reoxygenation. The NOS inhibitors 7‐nitroindazole (7‐NI) and N (G)‐nitro‐ l ‐arginine methyl ester ( l ‐NAME), as well as the Ca 2+ channel blocker nimodipine, reduced hypoxia‐induced LDH, suggesting that nitric oxide (NO) and calcium homeostasis contribute to hypoxia and/or the reoxygenation‐induced cell injury. The levels of nNOS immunoactivities and mRNA by RT‐PCR were enhanced by hypoxia with time and, down regulated following 24 h reoxygenation after hypoxia, and were attenuated by MK801. In addition, the reduction of nNOS mRNA levels by hypoxia/reoxygenation was also diminished by MK801. Further delineation of the mechanisms of NO production and nNOS regulation are needed and may lead to additional strategies to protect neuronal cells against hypoxic/reoxygenation insults. J. Cell. Biochem. 84: 367–376, 2002. © 2001 Wiley‐Liss, Inc.