Effects of nerve growth factor on nitric oxide-mediated neurotoxicity in primary cortical cultures.
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.


CONCLUSIONS
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.
Wu
J
J
Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China.
Zhang
J
J
D000818:Animals; D016923:Cell Death; D015687:Cell Hypoxia; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000473:pathology*; D005333:Fetus; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009474:Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052248:Nitric Oxide Synthase Type I; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats
D018696:Neuroprotective Agents; D012333:RNA, Messenger; D009569:Nitric Oxide; D020932:Nerve Growth Factor; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat