New evaluation system of cell damage caused by environmental chemicals that effect lifestyle diseases

影响生活方式疾病的环境化学物质造成的细胞损伤的新评估系统

• 批准号: 15310033
• 负责人: ISHII Tetsuro
• 金额: $ 9.98万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15310033/
• 关键词: Prx I; Fe-NTA; HO-1; A170; Nrf2; CD36; A549; phenanthraquinone; ニトロキシルラジカル; スルフォラファン; HSP70; ヒ素; キノン; Cu,Zn-SOD; パーオキシレドキシン

1.Cytotoxicity of phenanthraquinone contained in diesel exhaust particlesPhenanthraquinone showed strong toxicity to cultured human A549 cells derived from lung. Phenanthroline protected cells from toxicity of phenanthraquinone.2.Cytotoxicity of arsenic compoundsArsenic activates transcription factor Nrf2 and activate expression of genes such as HO-1,Prx I and A170, the protein accumulated as ubiquitin-conjugated form. Sulforaphane, Nrf2 activating natural compounds, had a beneficial effects against arsenic toxicity.3.Analysis of model mice in lifestyle-related illnessesWe constructed Prx I-deficient transgenic mice. The mutant mice showed higher sensitivity of tissue oxidative damage to Fe-NTA. The mice showed lower capacity to remove nitroxyl radicals. We also constructed A170-deficient mice. These mice show overeating and obesity, causing insulin-resistance.

1.柴油机尾气颗粒物中菲醌的细胞毒性菲醌对体外培养的人肺A549细胞有较强的毒性作用。2.砷化合物的细胞毒性砷激活转录因子Nrf 2并激活HO-1、Prx I和A170等基因的表达，蛋白质以泛素结合形式积累。萝卜硫素是一种激活Nrf 2的天然化合物，对砷中毒具有保护作用。3.生活方式相关疾病模型小鼠的分析突变小鼠对Fe-NTA的组织氧化损伤表现出更高的敏感性。小鼠清除硝酰基自由基的能力较低。我们还构建了A170缺陷型小鼠。这些老鼠表现出暴饮暴食和肥胖，导致胰岛素抵抗。

项目成果

Aono J.: "Activation of Nrf2 and accumulation of ubiquityinated A170 by arsenic in osteoblasts"Biochem.Biophys.Res.Commun.. 305. 271-277 (2003)

Aono J.：“成骨细胞中砷对 Nrf2 的激活和泛素化 A170 的积累”Biochem.Biophys.Res.Commun.. 305. 271-277 (2003)

Distinct roles of c-Abl and Atm in oxidative stress response are mediated by protein kinase C delta.

c-Abl 和 Atm 在氧化应激反应中的独特作用由蛋白激酶 C δ 介导。

• 发表时间: 2004
• 期刊: Genes Dev. 18
• 作者: Li;B.et al.
• 通讯作者: B.et al.

Activation of Nrt2 and accumulation of ubiquitinated A170 by arsenic in osteoblasts

砷在成骨细胞中激活 Nrt2 并积累泛素化 A170

• 发表时间: 2003
• 期刊: Biochem.Biophys.Res Commun. 305
• 作者: Yanagawa T.他;Aono J.他;Anwar AA.他;Sugimoto R.;Katsuoka F.;Uwayama J.;Yanagawa T.;Yanagawa T.;Aono J.;Anwar AA.;Katsuoka F. 他;Uwayama J. 他;Yanagawa T. 他;Aono J. 他;R.Sugimoto 他;Itoh K.他;Ishii T.他;Nakaso K.他;Ishii K.他;Itoh K.;Ishii T.;Nakaso K.;Ishii K.;Yanagawa T.;Li B.;K.Ishii 他;K.Nakaso 他;T.Yanagawa 他;B.Li 他;Aono J.他;石井哲郎 他;Aono J.
• 通讯作者: Aono J.

Tissue Prx I in the protection against Fe-NTA and the reduction of nitroxyl radicals.

组织 Prx I 具有针对 Fe-NTA 的保护和减少硝酰自由基的作用。

• 发表时间: 2006
• 期刊: Biochem. Biophys. Res. Commun. 339
• 作者: Uwayama;J.;et al.
• 通讯作者: et al.

酸化ストレスマーカー

氧化应激标记物

• 发表时间: 2005
• 作者: 宮澤陽夫;都築毅;仲川清隆;Yosuke Amagai;宮澤陽夫;He W.;宮澤陽夫;Keitaro Ohmori;宮澤陽夫
• 通讯作者: 宮澤陽夫