title: Neuronal NOS inhibitor that reduces oxidative DNA lesions and neuronal sensitivity increases the expression of intact c-fos transcripts after brain injury.
abstract: In response to oxidative stress, the ischemic brain induces immediate early genes when its nuclear genes contain gene damage. Antioxidant that reduces gene damage also reduces cell death. To study the mechanism of neuronal sensitivity, we investigated the transcription of the c-fos gene after brain injury of the ischemia-reperfusion type using focal cerebral ischemia-reperfusion in Long-Evans hooded rats. We observed a significant (p < 0.01) increase in c-fos mRNA in the ischemic cortex immediately after brain injury. However, the c-fos transcript was sensitive to RNase A protection assay (RPA) upon reperfusion. The transcript became significantly resistant to RPA (42%, p < 0.03) when 3-bromo-7-nitroindazole (25 mg/kg, i.p.), known to abolish nitric oxide, gene damage and neuronal sensitivity, was injected. Our data suggest that neuronal nitric oxide synthase and aberrant mRNA from genes with oxidative damage could be associated with neuronal sensitivity.
authors.affiliation: Department of Neurosurgery, Baylor College of Medicine, Houston, Tex 77030, USA.
authors.forename: J
authors.initials: J
authors.lastname: Cui
authors.forename: P K
authors.initials: PK
authors.lastname: Liu
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000235:genetics*; D004249:DNA Damage / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D017403:In Situ Hybridization; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D018384:Oxidative Stress; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D004791:Enzyme Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat