Study on a new defence system against oxidative stress

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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.