Oxidative stress regulation through NO-induced nucleic acid nitration in pulmonary diseases

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8-nitroguanosine, a modified base, draws people's attention as a marker for nucleic acid damage during carcinogenesis or other gene modification. Since we have succeeded in producing a specific antibody against 8-nitroguanosine, we studied the generation and localization of 8-nitroguanosine in various pulmonary diseases using the antibody.In pulmonary fibrosis, strong immunostaining for 8-nitroguanosine was observed in metaplastic epithelial cells as well as macrophages and alveolar epithelia. Colocalization of 8-nitroguanosine with iNOS, eNOS, hemoxygenase-1, 8-nitotyrosine, and p53 was detected in confocal laser scanning microscopy. In lung cancer, 8-nitroguanosine is observed both in cytoplasm and nuclei of cancer cells. These results suggest that 8-nitroguanosin is involved in injury of air-space epithelia and also in pulmonary carcinogenesis. In lung injury mouse models induced by hyperoxia-exposure or bleomycin showed that 8-nitorguanosine is generated in air-space epitheial cells as well as in macrophages accumulated in injured tissue indicating that 8-nitroguanosine is involved in such disease processes.We have previously shown that 8-nitro-cyclic GMP, a nitroguanosine derivative, activates cell survival by inducing hemoxigenase-1 and other cytoprotective molecules. It is considered that 8-nitoroguanosine is not a silent damaged base but a highly active molecule possessing signaling transmittal function.