文章基本信息

标题：Nrf2 is essential for protection against acute pulmonary injury in mice
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作者：Kaimin Chan ; Yuet Wai Kan
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1999
卷号：96
期号：22
页码：12731-12736
DOI：10.1073/pnas.96.22.12731
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Nrf2 is a member of the "cap n' collar" family of transcription factors. These transcription factors bind to the NF-E2 binding sites (GCTGAGTCA) that are essential for the regulation of erythroid-specific genes. Nrf2 is expressed in a wide range of tissues, many of which are sites of expression for phase 2 detoxification genes. Nrf2-/- mice are viable and have a normal phenotype under normal laboratory conditions. The NF-E2 binding site is a subset of the antioxidant response elements that have the sequence GCNNNGTCA. The antioxidant response elements are regulatory sequences found on promoters of several phase 2 detoxification genes that are inducible by xenobiotics and antioxidants. We report here that Nrf2-/- mice are extremely susceptible to the administration of the antioxidant butylated hydroxytoluene. With doses of butylated hydroxytoluene that are tolerated by wild-type mice, the Nrf2-/- mice succumb from acute respiratory distress syndrome. Gene expression studies show that the expression of several detoxification enzymes is altered in the Nrf2-/- mice. The Nrf2-/- mice may prove to be a good in vivo model for toxicological studies. As oxidative damage causes DNA breakage, these mice may also be useful for testing carcinogenic agents.
关键词：butylated hydroxytoluene ; butylated hydroxyanisole ; antioxidant response element ; gene knockout ; acute respiratory distress syndrome