The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress.
A major mechanism in the cellular defense against oxidative or electrophilic stress is activation of the Nrf2-antioxidant response element signaling pathway, which controls the expression of genes whose protein products are involved in the detoxication and elimination of reactive oxidants and electrophilic agents through conjugative reactions and by enhancing cellular antioxidant capacity. At the molecular level, however, the regulatory mechanisms involved in mediating Nrf2 activation are not fully understood. It is well established that Nrf2 activity is controlled, in part, by the cytosolic protein Keap1, but the nature of this pathway and the mechanisms by which Keap1 acts to repress Nrf2 activity remain to be fully characterized and are the topics of discussion in this minireview. In addition, a possible role of the Nrf2-antioxidant response element transcriptional pathway in neuroprotection will also be discussed.
Nguyen
Truyen
T
Schering-Plough Research Institute, Summit, New Jersey 07901, USA.
Nioi
Paul
P
Pickett
Cecil B
CB
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000975:Antioxidants; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D000072019:Kelch-Like ECH-Associated Protein 1; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis* / Q000235:genetics; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020218:Response Elements / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D000975:Antioxidants; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; C117301:Keap1 protein, mouse; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species