期刊
TRENDS IN MOLECULAR MEDICINE
卷 10, 期 11, 页码 549-557出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.molmed.2004.09.003
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The transcription factor Nrf2 regulates the basal and inducible expression of numerous detoxifying and antioxidant genes. The cytoplasmic protein Keap1 interacts with Nrf2 and represses its function. Analysis of keap1-knockout mice provides solid evidence that Keap1 acts as a negative regulator of Nrf2 and as a sensor of xenobiotic and oxidative stresses. The simultaneous ablation of the keap1 and nrf2 genes reversed all apparent phenotypes of the Keap1-deficient mice, suggesting that NrF2 is a primary target of Keap1. The Nrf2-Keap1 system is now recognized as one of the major cellular defence mechanisms against oxidative and xenobiotic stresses. Furthermore, extensive studies have suggested that the Nrf2-Keap1 system contributes to protection against various pathologies, including carcinogenesis, liver toxicity, respiratory distress and inflammation.
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