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Effects of nerve growth factor on nitric oxide-mediated neurotoxicity in primary cortical cultures
1Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China.
Objective:
To observe the effects of nerve growth factor (NGF) on nitric oxide (NO) release and constitutive nitric oxide synthase (cNOS) gene expression in oxygen/glucose deprived cortical neuron cultures.
Methods:
Neuron viability was measured to assay NGF effect. The content of NO and the expression of cNOS mRNA were determined by spectrofluorometric method and Northern blot respectively.
Results:
There were a marked increase of neuronal death and NO release in oxygen/glucose deprived cultures for 24 h. NOS inhibitor, NG-nitro-L-arginine methyl ester (NAME) 100 mumol.L-1 and NGF 50, 100 micrograms.L-1, significantly increased neuronal surviving and decreased NO release. However, NGF (50, 100 micrograms.L-1) had no significant effects on neurotoxicity induced by sodium nitroprusside (SNP) 300 mumol.L-1 in cortical cultures. Hemoglobin (Hb), which binds NO, completely prevented hypoxia/hypoglycemia- or SNP-induced cell death and NO release at 500 mumol.L-1. NGF 100 micrograms.L-1 significantly attenuated cNOS gene expression.
Conclusion:
NO can mediate the neurotoxicity of hypoxia/hypoglycemia, and NGF can protect cortical neurons against oxygen/glucose deprivation-induced toxicity via inhibiting the activity of cNOS and suppressing the release of NO.