Study on a new defence system against oxidative stress

新型氧化应激防御系统的研究

• 批准号: 11470038
• 负责人: ISHII Tetsuo
• 金额: $ 9.28万
• 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: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470038/
• 关键词: Nrf2; HO-1; Prx I; A170; LDL; Prx I; MSP23

We found that transcription factor Nrf2, known to interact with electrophile response elements or antioxidant responsive elements, regulates expression of detoxifying enzymes and antioxidant proteins such as HO-1, Prx I, A170 and the cystine transporter in murine peritoneal macrophages. Nrf2 was activated by various types of oxidative stress-causing agents : low levels of H_2O_2 that is added to the medium or produced by glucose oxidase in the culture medium, paraquat that produces superoxide, arsenite, cadmium, and electrophilic agents such as diethylmaleate and catechol. Nrf2 also controlled expression of genes encoding detoxifying enzymes such as GSTs and NQO1 in small intestine and liver by dietary 2(3)-t-butyl-4-hydroxyanisole (BHA). We found that dietary BHA induced intestinal and hepatic Prx I in a manner similar to the induction of GSTs. Thus, Nrf2 plays important roles in defense against various types of cytotoxic agents.

我们发现，转录因子Nrf 2，已知与亲电反应元件或抗氧化剂反应元件相互作用，调节解毒酶和抗氧化蛋白，如HO-1，Prx I，A170和胱氨酸转运蛋白在小鼠腹腔巨噬细胞的表达。Nrf 2可被多种氧化应激因子激活：低水平的H_2O_2（添加到培养基中或由培养基中的葡萄糖氧化酶产生）、百草枯（产生超氧化物）、亚砷酸盐、镉以及亲电因子（如马来酸二乙酯和邻苯二酚）。Nrf 2还通过饮食2（3）-叔丁基-4-羟基茴香醚（BHA）控制小肠和肝脏中编码解毒酶（如GST和NQO 1）的基因表达。我们发现，饮食BHA诱导肠和肝Prx我的方式类似的GST诱导。因此，Nrf 2在防御各种类型的细胞毒性剂中起重要作用。

项目成果

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