The involvement of dihydropyrazine-induced gene damage in diabetic complication

二氢吡嗪诱导的基因损伤与糖尿病并发症的关系

• 批准号: 23590160
• 负责人: ISHIDA TAKUMI
• 金额: $ 3.41万
• 依托单位: Sojo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590160/
• 关键词: ジヒドロピラジン; 糖化反応; 毒性; 酸化的ストレス; 糖尿病; 細胞障害; HepG2 細胞; ジヒドロピラジン類; 細胞障害性; グルタチオンバランス; 糖化反応中間体; 遺伝子障害

Dihydropyrazines (DHPs), formed by nonenzymatic glycation, are known to exert various effects in vitro and in vivo. In this study, we investigated the effects of DHP on human hepatoma HepG2 cells using 2,3-dihydro-5,6-dimethylpyrazine (DHP-1), 2,3-dihydro-2,5,6-trimethylpyrazine (DHP-2), and 3-hydro-2,2,5,6-tetramethylpyrazine (DHP-3) as model compounds. All of the tested compounds exerted cytotoxic activity against HepG2 cells, and significantly so at the highest concentration. DHP-3 was the most cytotoxic drug. Additionally, DHP-3 exposure showed the significant increase of heme oxygenase-1 and glutamate cysteine ligase catalytic subunit mRNA after exposure. The serum concentration of DHPs in diabetic patient showed significant increase compared with that in non-diabetic patient. Therefore, These results suggested that the Nrf2-ARE signal pathway activated by oxidative stress is in part involved in the effect of DHP on mammalian cells.

二氢吡嗪（DHP）由非酶糖化形成，已知在体外和体内发挥多种作用。在本研究中，我们使用 2,3-二氢-5,6-二甲基吡嗪 (DHP-1)、2,3-二氢-2,5,6-三甲基吡嗪 (DHP-2) 和 3-氢-2,2,5,6-四甲基吡嗪 (DHP-3) 作为模型化合物，研究了 DHP 对人肝癌 HepG2 细胞的影响。 所有测试的化合物均对 HepG2 细胞发挥细胞毒活性，并且在最高浓度下效果显着。 DHP-3是最具细胞毒性的药物。此外，DHP-3 暴露显示暴露后血红素加氧酶-1 和谷氨酸半胱氨酸连接酶催化亚基 mRNA 显着增加。糖尿病患者血清DHPs浓度较非糖尿病患者显着升高。因此，这些结果表明氧化应激激活的Nrf2-ARE信号通路部分参与了DHP对哺乳动物细胞的作用。

项目成果

糖化反応中間体 dihydropyrazine 類による細胞障害発現機構

糖化反应中间体二氢吡嗪引起细胞损伤的机制

• 发表时间: 2012
• 作者: Yanagihara N.;Seki M.;Nakano M.;Hachisuga T.;Goto Y;情野秀晃,稲見圭子,望月正隆;石田卓巳
• 通讯作者: 石田卓巳

糖化反応中間体 dihydropyrazine 類による毒性発現機構の解析

糖化反应中间体二氢吡嗪的毒性机制分析

• 作者: 松岡美里;石田卓巳;武知進士
• 通讯作者: 武知進士