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The Nrf2 System as a Potential Target for the Development of Indirect Antioxidants
College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongsangbuk-do 712-749, Korea
* Author to whom correspondence should be addressed.
Received: 19 September 2010; in revised form: 18 October 2010 / Accepted: 20 October 2010 / Published: 20 October 2010
Abstract: Oxidative stress causes damage to multiple cellular components such as DNA, proteins, and lipids, and is implicated in various human diseases including cancer, neurodegeneration, inflammatory diseases, and aging. In response to oxidative attack, cells have developed an antioxidant defense system to maintain cellular redox homeostasis and to protect cells from damage. The thiol-containing small molecules (e.g. glutathione), reactive oxygen species-inactivating enzymes (e.g. glutathione peroxidase), and phase 2 detoxifying enzymes (e.g. NAD(P)H: quinine oxidoreductase 1 and glutathione-S-transferases) are members of this antioxidant system. NF-E2-related factor 2 (Nrf2) is a CNC-bZIP transcription factor which regulates the basal and inducible expression of a wide array of antioxidant genes. Following dissociation from the cytosolic protein Keap1, a scaffolding protein which binds Nrf2 and Cul3 ubiquitin ligase for proteasome degradation, Nrf2 rapidly accumulates in the nucleus and transactivates the antioxidant response element in the promoter region of many antioxidant genes. The critical role of Nrf2 has been demonstrated by various animal studies showing that mice with a targeted disruption of the nrf2 gene are prone to develop lesions in response to environmental toxicants/carcinogens, drugs, and inflammatory insults. In this review, we discuss the role of the Nrf2 system, with particular focus on Nrf2-controlled target genes and the potential pleiotropic effects of Nrf2 activation of indirect antioxidants.
Keywords: indirect antioxidants; oxidative stress; Nrf2; Keap1
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Jung, K.-A.; Kwak, M.-K. The Nrf2 System as a Potential Target for the Development of Indirect Antioxidants. Molecules 2010, 15, 7266-7291.
Jung K-A, Kwak M-K. The Nrf2 System as a Potential Target for the Development of Indirect Antioxidants. Molecules. 2010; 15(10):7266-7291.
Jung, Kyeong-Ah; Kwak, Mi-Kyoung. 2010. "The Nrf2 System as a Potential Target for the Development of Indirect Antioxidants." Molecules 15, no. 10: 7266-7291.