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

通过 NO 诱导的核酸硝化调节肺部疾病中的氧化应激

• 批准号: 17590797
• 负责人: TAKAHASHI Kiyoshi
• 金额: $ 2.24万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590797/
• 关键词: 8-nitoroguanosine; carcinogenesis; gene modification; pulmonary fibrosis; hyperoxia-induced lung injury; survival siganl; nucleic acid damage; animal model

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.

8-硝基鸟苷作为一种修饰过的碱基，作为致癌或其他基因修饰过程中核酸损伤的标记物，引起了人们的关注。由于我们已经成功制备了针对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，在化生上皮细胞、巨噬细胞和肺泡上皮中观察到8-硝基鸟苷的强免疫染色。用激光共聚焦扫描显微镜检测8-硝基鸟苷与iNOS、eNOS、血氧合酶- 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细胞质和细胞核中。这些结果提示8-硝基鸟苷参与了肺上皮的损伤和肺癌的发生。在高氧暴露或博来霉素诱导的肺损伤小鼠模型中，8-硝基鸟苷在空腔上皮细胞和损伤组织中积累的巨噬细胞中产生，表明8-硝基鸟苷参与了这一疾病过程。我们之前已经证明，8-硝基环GMP，一种硝基鸟苷衍生物，通过诱导血红素-1和其他细胞保护分子来激活细胞存活。认为8-硝基鸟苷不是一种沉默的受损碱基，而是一种具有信号传递功能的高活性分子。

项目成果

Clearance of apoptotic cells is not impaired in mouse embryos deficient in class A scavenger receptor types I and II (CD204)

• DOI: 10.1002/dvdy.20206
• 发表时间: 2005-01-01
• 期刊: DEVELOPMENTAL DYNAMICS
• 影响因子: 2.5
• 作者: Komohara, Y;Terasaki, Y;Takeya, M
• 通讯作者: Takeya, M

Protein S-guanylation by the biological signal 8-nitroguanosine 3′,5′-cyclic monophosphate

• DOI: 10.1038/nchembio.2007.33
• 发表时间: 2007-11-01
• 期刊: NATURE CHEMICAL BIOLOGY
• 影响因子: 14.8
• 作者: Sawa, Tomohiro;Zaki, Mohammad Hasan;Akaike, Takaaki
• 通讯作者: Akaike, Takaaki

Nitric oxide-induced nitrative stress involved in microbial pathogenesis.

• DOI: 10.1254/jphs.crj05004x
• 发表时间: 2005
• 期刊: Journal of pharmacological sciences
• 影响因子: 3.5
• 作者: M. Zaki;T. Akuta;T. Akaike

Detection of guinea pig macrophages by a new CD68 monoclonal antibody, PM-1K

使用新型 CD68 单克隆抗体 PM-1K 检测豚鼠巨噬细胞

• 发表时间: 2006
• 期刊: J Mol Histol 37・1
• 作者: Horikawa T;Komohara Y;Kiyota E;Terasaki Y;Takagi K;Takeya M.
• 通讯作者: Takeya M.

Guanine nitration in idiopathic pulmonary fibrosis and its implication for carcinogenesis

特发性肺纤维化中的鸟嘌呤硝化及其对癌发生的影响

• 发表时间: 2007
• 期刊: Lung Cancer Update 46
• 作者: Akaike T;and Okamoto T.
• 通讯作者: and Okamoto T.