|2004.03.31; 37(2) pp. 139~143|
An Important Role of Nrf2-ARE Pathway in the Cellular Defense Mechanism
Jong-Min Lee¢Ó,¢Ô and Jeffrey A. Johnson¢Ó,¢Ô,¡×,||,*
¢ÓSchool of Pharmacy, ¢ÔMolecular and Environmental Toxicology Center, ¡×Waisman Center, ||Center for Neuroscience, University of Wisconsin, Madison, WI 53705, USA
The antioxidant responsive element (ARE) is a cis-acting regulatory element of genes encoding phase II detoxification enzymes and antioxidant proteins, such as NAD(P)H: quinone oxidoreductase 1, glutathione S-transferases, and glutamate-cysteine ligase. Interestingly, it has been reported that Nrf2 (NF-E2-related factor 2) regulates a wide array of ARE-driven genes in various cell types. Nrf2 is a basic leucine zipper transcription factor, which was originally identified as a binding protein of locus control region of ©¬-globin gene. The DNA binding sequence of Nrf2 and ARE sequence are very similar, and many studies demonstrated that Nrf2 binds to the ARE sites leading to up-regulation of downstream genes. The function of Nrf2 and its downstream target genes suggests that the Nrf2-ARE pathway is important in the cellular antioxidant defense system. In support of this, many studies showed a critical role of Nrf2 in cellular protection and anti-carcinogenicity, implying that the Nrf2-ARE pathway may serve as a therapeutic target for neurodegenerative diseases and cancers, in which oxidative stress is closely implicated.
Antioxidant responsive element, Nrf2