An important role of Nrf2-ARE pathway in the cellular defense mechanism.
By Jong‐Min Lee, Jeffrey A. Johnson. Journal of biochemistry and molecular biology, 2004
771 citations recorded by the source corpus.
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 beta-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.
Subfields: Molecular Biology, Plant Science
View Paper: https://www.semanticscholar.org/paper/91d1a7a720fd49ac1661bf6b84baa752960277d7
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Citations in the corpus
- Glutathione dysregulation and the etiology and progression of human diseases (2009, background): “g-Glutamylcysteine ligase expression is subject to regulation by Nrf2, a transcription factor that regulates a wide array of antioxidant responsive element-driven genes in various cell types, and thus plays a central role in cellular antioxidant defenses (Wild and Mulcahy, 2000; Jaiswal, 2004; Lee a”
- Small Molecule Modulators of Keap1-Nrf2-ARE Pathway as Potential Preventive and Therapeutic Agents (2012, background): “Investigation of ARE-inducing activities of monocyclic systems such as MCE-1 (27) and MCE5 (28) demonstrated that 27 was approximately twofold less potent than 26, but approximately tenfold more potent than 28.”
- Expression of Nrf2 in Neurodegenerative Diseases (2007, positive): “The Nrf2 transcription factor controls expression of the genes necessary to reduce oxidative stress (30).”
- Measurement and Clinical Significance of Biomarkers of Oxidative Stress in Humans (2017, background): “The ARE/ Nrf2 pathway is the major player in the induction of the expression of antioxidant genes [309].”
- The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state (2015, neutral): “against oxidative/nitrosative stress [73].”
- Novel mechanisms of natural antioxidant compounds in biological systems: involvement of glutathione and glutathione-related enzymes. (2005, background): “Gel shift experiments showed that Nrf2 protein binds strongly to the ARE sequence and positively regulates its activity [134].”
- ROS and ROS-Mediated Cellular Signaling (2016, background): “cellular components: Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and antioxidant response elements (ARE) [71–76].”