Molecular regulatory mechanisms of NO analyzed by using nitronyl nitroxide

利用硝基硝基氧分析NO的分子调控机制

• 批准号: 15087207
• 负责人: AKAIKE Takaaki
• 金额: $ 18.43万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15087207/
• 关键词: NO; redox signal; signal transduction; adaptive response; radical; cell death; 8-nitroguanosine; 8-ニトロ-cGMP; 核酸ニトロ化; ヘムオキシゲナーゼー1; 核酸にニトロ化; ヘムオキシゲナーゼ-1; Nitronyl nitroxide; NOセンサー; NO消去剤; NO分子機能制御; PTIO; 細胞シグナル; 細胞保護作用

Nitric oxide (NO) has been suggested to be involved in the pathogenesis of various diseases, including infections, inflammatory diseases, and cancer. We have demonstrated the occurrence of nitratively modified nucleic acids (e.g., 8-nitroguanosine and 8-nitroguanine) in precancerous and cancer tissues, including idiopathic pulmonary fibrosis and human lung cancer, and in urine of smokers. In this study, we identified the formation of novel nitrated cyclic nucleotide, 8-nitroguano sine-3', 5'-cyclic monophosphate (8-nitro-c GMP), in macrophages stimulated with inflammatory cytokine. 8-Nitro-cGMP possesses cGMP-dependent protein kinase-activating potential and unique signal functions independent of cGMP activity. Of great importance is a novel post-translational modification (8-thioalkoxy-cGMP adduct formation) of proteins induced by 8-nitro-cGMP, coined S-guanylation. For example, a redox-sensor signal protein Keap 1 appears to be regulated by 8-nitro-cGMP, via S-guanylation of highly nucleophilic Cys sulfhydrils of Keap 1, leading to the induction of stress adaptive response signals. This study revealed 8-nitro-cGMP to be asecond messenger of NO and shed light on new areas of pathophysiology and chemical biology of signal transduction by NO and cGMP.

一氧化氮（NO）已被认为参与多种疾病的发病机制，包括感染、炎症性疾病和癌症。我们已经证实，在癌前组织和癌症组织中，包括特发性肺纤维化和人类肺癌，以及吸烟者的尿液中，存在硝酸修饰的核酸（例如，8-硝基鸟嘌呤和8-硝基鸟嘌呤）。在这项研究中，我们发现在炎症细胞因子刺激的巨噬细胞中形成了新的硝化环核苷酸，8-硝基鸟嘌呤-3′，5′-环单磷酸（8-硝基-c GMP）。8-硝基cGMP具有cGMP依赖性蛋白激酶激活电位和独立于cGMP活性的独特信号功能。重要的是一种新的翻译后修饰（8-硝基- cgmp加合物形成），被称为s -胍基化。例如，氧化还原传感器信号蛋白Keap 1似乎受到8-硝基- cgmp的调节，通过对Keap 1高度亲核的Cys巯基进行s -胍基化，从而诱导应激适应反应信号。本研究揭示了8-硝基cGMP是NO的第二信使，为NO和cGMP信号转导的病理生理和化学生物学研究开辟了新的领域。

项目成果

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

Interleukin-1β induces death in chondrocyte-like ATDC5 cells through mitochondrial dysfunction and energy depletion in a reactive nitrogen and oxygeh species-dependent manner.

Interleukin-1β 通过线粒体功能障碍和能量消耗以活性氮和氧物种依赖性方式诱导软骨细胞样 ATDC5 细胞死亡。

• 发表时间: 2005
• 期刊: Biochem. J. 389
• 作者: Yasuhara;R. et al.
• 通讯作者: R. et al.

Proapoptotic effect of proteolytic activation of matrix metalloproteinases by Streptococcus pyogenes thiol proteinase/Streptococcus pyrogenic exotoxin B.

化脓性链球菌硫醇蛋白酶/致热链球菌 B 型外毒素对基质金属蛋白酶的蛋白水解激活的促凋亡作用。

• 发表时间: 2004
• 期刊: Infect. Immun. 72
• 作者: Tamura;F. et al.
• 通讯作者: F. et al.

Adsorption and infectivity of human immunodeficiency virus type 1 are modified by the fluidity of the plasma membrane for multiple-site binding.

1 型人类免疫缺陷病毒的吸附和感染性通过质膜的流动性进行多位点结合而改变。

• 发表时间: 2004
• 期刊: Micobiol. Immunol. 48
• 作者: Harada;S. et al.
• 通讯作者: S. et al.

Tanaka, S.et al.: "Modulation of tumor-selective vascular blood flow and extravasation by stable prostaglandin I_2 analogue, beraprost sodium."J.Drug Target.. 11. 45-51 (2003)

Tanaka, S.et al.：“通过稳定的前列腺素 I_2 类似物贝前列素钠调节肿瘤选择性血管血流和外渗。”J.Drug Target.. 11. 45-51 (2003)