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

8-硝基鸟苷是一种修饰的碱基，在致癌或其他基因修饰过程中作为核酸损伤的标志而引起人们的注意。由于我们已经成功地制备了针对8-硝基鸟苷的特异性抗体，我们利用该抗体研究了8-硝基鸟苷在各种肺部疾病中的产生和定位。在肺纤维化中，8-硝基鸟苷在化生上皮细胞以及巨噬细胞和肺泡上皮细胞中有较强的免疫染色。共聚焦激光扫描显微镜观察8-硝基鸟苷与iNOS、eNOS、HO-1，8-硝基酪氨酸和P53的共定位。在肺癌中，8-硝基鸟苷存在于癌细胞的胞浆和胞核中。这些结果提示，8-硝基鸟苷参与了肺上皮细胞的损伤和肺癌的发生。在高氧暴露或博莱霉素诱导的小鼠肺损伤模型中，8-硝基鸟苷在肺损伤组织中积聚的气隙上皮细胞和巨噬细胞中产生，表明8-硝基鸟苷参与了这种疾病的过程。我们先前已经证明，8-硝基鸟苷是一种硝基鸟苷衍生物，通过诱导血氧合酶-1和其他细胞保护分子来激活细胞存活。认为8-硝基鸟苷不是沉默的受损碱基，而是一种具有信号传递功能的高活性分子。

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.