Genomes and Genes
nf e2 related factor 2
Summary: A basic-leucine zipper transcription factor that was originally described as a transcriptional regulator controlling expression of the BETA-GLOBIN gene. It may regulate the expression of a wide variety of genes that play a role in protecting cells from oxidative damage.
- Nguyen T, Nioi P, Pickett C. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem. 2009;284:13291-5 pubmed publisher..In addition, a possible role of the Nrf2-antioxidant response element transcriptional pathway in neuroprotection will also be discussed. ..
- Siebert A, Desai V, Chandrasekaran K, Fiskum G, Jafri M. Nrf2 activators provide neuroprotection against 6-hydroxydopamine toxicity in rat organotypic nigrostriatal cocultures. J Neurosci Res. 2009;87:1659-69 pubmed publisher..Overall, these results suggest that Nrf2 may play an important role in cellular protection in neurodegenerative diseases and may be a viable therapeutic target in the future. ..
- Liu M, Grigoryev D, Crow M, Haas M, Yamamoto M, Reddy S, et al. Transcription factor Nrf2 is protective during ischemic and nephrotoxic acute kidney injury in mice. Kidney Int. 2009;76:277-85 pubmed publisher..Our study demonstrates that Nrf2-deficiency enhances susceptibility to both ischemic and nephrotoxic acute kidney injury, and identifies this transcription factor as a potential therapeutic target in these injuries. ..
- Duan W, Zhang R, Guo Y, Jiang Y, Huang Y, Jiang H, et al. Nrf2 activity is lost in the spinal cord and its astrocytes of aged mice. In Vitro Cell Dev Biol Anim. 2009;45:388-97 pubmed publisher..Total nuclear factor E2-related factor 2, which governs basal and inducible expression of HO1 and NQO1, decreased significantly. Significantly, epigallocatechin gallate restored the Nrf2 activity. ..
- Burdette D, Olivarez M, Waris G. Activation of transcription factor Nrf2 by hepatitis C virus induces the cell-survival pathway. J Gen Virol. 2010;91:681-90 pubmed publisher..Taken together, these results provide an insight into the mechanisms by which HCV induces intracellular events relevant to chronic HCV infection. ..
- Sekhar K, Rachakonda G, Freeman M. Cysteine-based regulation of the CUL3 adaptor protein Keap1. Toxicol Appl Pharmacol. 2010;244:21-6 pubmed publisher..Thus, adduction captures specific chemical information and translates it into biochemical information via changes in structural conformation. ..
- Pitha Rowe I, Liby K, Royce D, Sporn M. Synthetic triterpenoids attenuate cytotoxic retinal injury: cross-talk between Nrf2 and PI3K/AKT signaling through inhibition of the lipid phosphatase PTEN. Invest Ophthalmol Vis Sci. 2009;50:5339-47 pubmed publisher..Thus the stimulation of AKT activity is mediated by TP inhibition of PTEN activity. These studies highlight the potential of TPs in retinal cytoprotection and implicate PTEN inhibition as a target in cytoprotection. ..
- Akhdar H, Loyer P, Rauch C, Corlu A, Guillouzo A, Morel F. Involvement of Nrf2 activation in resistance to 5-fluorouracil in human colon cancer HT-29 cells. Eur J Cancer. 2009;45:2219-27 pubmed publisher..Therefore, we postulate that Nrf2 might represent a potential therapeutic target in 5-FU treatment of colon cancer. ..
- Li J, Ichikawa T, Janicki J, Cui T. Targeting the Nrf2 pathway against cardiovascular disease. Expert Opin Ther Targets. 2009;13:785-94 pubmed publisher..Herein, we review the current literature that suggests that Nrf2 is a valuable therapeutic target for cardiovascular disease, as well as experiments that illustrate the mechanisms of Nrf2 cardioprotection. ..
- Choi H, Pokharel Y, Lim S, Han H, Ryu C, Kim S, et al. Inhibition of liver fibrosis by solubilized coenzyme Q10: Role of Nrf2 activation in inhibiting transforming growth factor-beta1 expression. Toxicol Appl Pharmacol. 2009;240:377-84 pubmed publisher..These results demonstrated that solubilized CoQ10 inhibited DMN-induced liver fibrosis through suppression of TGF-beta1 expression via Nrf2/ARE activation. ..
- Boutten A, Goven D, Boczkowski J, Bonay M. Oxidative stress targets in pulmonary emphysema: focus on the Nrf2 pathway. Expert Opin Ther Targets. 2010;14:329-46 pubmed publisher..The current literature suggests that among oxidative stress targets, Nrf2 is a valuable therapeutic target in pulmonary emphysema. ..
- Rojo A, Innamorato N, Martín Moreno A, De Ceballos M, Yamamoto M, Cuadrado A. Nrf2 regulates microglial dynamics and neuroinflammation in experimental Parkinson's disease. Glia. 2010;58:588-98 pubmed publisher..This study demonstrates a crucial role of Nrf2 in modulation of microglial dynamics and identifies Nrf2 as molecular target to control microglial function in Parkinson's disease (PD) progression. ..
- Sugimoto H, Okada K, Shoda J, Warabi E, Ishige K, Ueda T, et al. Deletion of nuclear factor-E2-related factor-2 leads to rapid onset and progression of nutritional steatohepatitis in mice. Am J Physiol Gastrointest Liver Physiol. 2010;298:G283-94 pubmed publisher..Activation of Nrf2 could be a promising target toward developing new options for prevention and treatment of steatohepatitis. ..
- Li J, Ichikawa T, Villacorta L, Janicki J, Brower G, Yamamoto M, et al. Nrf2 protects against maladaptive cardiac responses to hemodynamic stress. Arterioscler Thromb Vasc Biol. 2009;29:1843-50 pubmed publisher..These findings demonstrate that activation of Nrf2 provides a novel mechanism to protect the murine heart against pathological cardiac hypertrophy and heart failure via suppressing oxidative stress. ..
- Yates M, Tran Q, Dolan P, Osburn W, Shin S, McCulloch C, et al. Genetic versus chemoprotective activation of Nrf2 signaling: overlapping yet distinct gene expression profiles between Keap1 knockout and triterpenoid-treated mice. Carcinogenesis. 2009;30:1024-31 pubmed publisher..Additionally, analysis of pharmacologic activation suggests that Nrf2 is the primary mediator of CDDO-Im activity, though other cell-signaling targets are also modulated following an oral dose of 30 micromol/kg. ..
- Higgins L, Kelleher M, Eggleston I, Itoh K, Yamamoto M, Hayes J. Transcription factor Nrf2 mediates an adaptive response to sulforaphane that protects fibroblasts in vitro against the cytotoxic effects of electrophiles, peroxides and redox-cycling agents. Toxicol Appl Pharmacol. 2009;237:267-80 pubmed publisher..Thus Nrf2-dependent up-regulation of GSH is the principal mechanism by which sulforaphane pre-treatment induced resistance to acrolein, CuOOH and chlorambucil, but not menadione...
- Sasaki H, Hikosaka Y, Okuda K, Kawano O, Moriyama S, Yano M, et al. NFE2L2 gene mutation in male Japanese squamous cell carcinoma of the lung. J Thorac Oncol. 2010;5:786-9 pubmed publisher..0032, Breslow-Gehan-Wilcoxon test, p = 0.0028). NFE2L2 mutations might play a role in tumor prognosis of squamous cell carcinoma of the lung. ..
- Zhang J, Hung A, Ng P, Nakayama K, Hu Y, Li B, et al. PKCdelta mediates Nrf2-dependent protection of neuronal cells from NO-induced apoptosis. Biochem Biophys Res Commun. 2009;386:750-6 pubmed publisher..Hence, PKCdelta is an important positive modulator of NO-induced Nrf2/ARE-dependent signaling that counteracts NO-mediated apoptosis in neuronal cells. ..
- Trinh K, Andrews L, Krause J, Hanak T, Lee D, Gelb M, et al. Decaffeinated coffee and nicotine-free tobacco provide neuroprotection in Drosophila models of Parkinson's disease through an NRF2-dependent mechanism. J Neurosci. 2010;30:5525-32 pubmed publisher..These compounds represent attractive candidates for therapeutic intervention in PD and perhaps other neurodegenerative diseases. ..
- Malec V, Gottschald O, Li S, Rose F, Seeger W, Hänze J. HIF-1 alpha signaling is augmented during intermittent hypoxia by induction of the Nrf2 pathway in NOX1-expressing adenocarcinoma A549 cells. Free Radic Biol Med. 2010;48:1626-35 pubmed publisher..By using a proteasomal inhibitor, NOX1 was demonstrated to activate Nrf2 by protein stabilization. Subsequently, Nrf2-dependent Trx1 induction turned out to enhance HIF-1 alpha signaling in intermittent hypoxia. ..
- Shah Z, Li R, Ahmad A, Kensler T, Yamamoto M, Biswal S, et al. The flavanol (-)-epicatechin prevents stroke damage through the Nrf2/HO1 pathway. J Cereb Blood Flow Metab. 2010;30:1951-61 pubmed publisher..These results suggest that EC exerts part of its beneficial effect through activation of Nrf2 and an increase in the neuroprotective HO1 enzyme. ..
- Eggler A, Small E, Hannink M, Mesecar A. Cul3-mediated Nrf2 ubiquitination and antioxidant response element (ARE) activation are dependent on the partial molar volume at position 151 of Keap1. Biochem J. 2009;422:171-80 pubmed publisher..This model has significant implications for how electrophiles which modify Cys(151), disrupt the repressive function of Keap1. ..
- Jia L, Liu Z, Sun L, Miller S, Ames B, Cotman C, et al. Acrolein, a toxicant in cigarette smoke, causes oxidative damage and mitochondrial dysfunction in RPE cells: protection by (R)-alpha-lipoic acid. Invest Ophthalmol Vis Sci. 2007;48:339-48 pubmed
- Tripathi D, Jena G. Effect of melatonin on the expression of Nrf2 and NF-kappaB during cyclophosphamide-induced urinary bladder injury in rat. J Pineal Res. 2010;48:324-31 pubmed publisher..The results of the present study provide evidence that melatonin treatment favorably alters Nrf2 and NF-kappaB expression and, this appears to be at least in part responsible for observed protection against CP-induced urotoxicity. ..
- Miyazaki T, Kirino Y, Takeno M, Samukawa S, Hama M, Tanaka M, et al. Expression of heme oxygenase-1 in human leukemic cells and its regulation by transcriptional repressor Bach1. Cancer Sci. 2010;101:1409-16 pubmed publisher..Thus, functional upregulation of Bach1 is a potential strategy for antileukemic therapy. ..
- Zhang X, Zhao X, Ma Z. PYDDT, a novel phase 2 enzymes inducer, activates Keap1-Nrf2 pathway via depleting the cellular level of glutathione. Toxicol Lett. 2010;199:93-101 pubmed publisher..We concluded from our findings that conjugation with intracellular GSH by PYDDT might lead to Keap1 S-glutathionylation and was a key event involved in its Nrf2 inducing activity. ..
- Ogura T, Tong K, Mio K, Maruyama Y, Kurokawa H, Sato C, et al. Keap1 is a forked-stem dimer structure with two large spheres enclosing the intervening, double glycine repeat, and C-terminal domains. Proc Natl Acad Sci U S A. 2010;107:2842-7 pubmed publisher..This study thus provides a structural basis for the two-site binding and hinge-latch model of stress sensing by the Nrf2-Keap1 system. ..
- Leiser S, Miller R. Nrf2 signaling, a mechanism for cellular stress resistance in long-lived mice. Mol Cell Biol. 2010;30:871-84 pubmed publisher..Augmented activity of Nrf2 and ARE-responsive genes may coordinate many of the stress resistance traits seen in cells from these long-lived mutant mice. ..
- Espada S, Rojo A, Salinas M, Cuadrado A. The muscarinic M1 receptor activates Nrf2 through a signaling cascade that involves protein kinase C and inhibition of GSK-3beta: connecting neurotransmission with neuroprotection. J Neurochem. 2009;110:1107-19 pubmed publisher..Such role provides additional conceptual support for the use of cholinemimetics in the treatment of pathologies that, like Alzheimer's disease, require a reinforcement of the cell antioxidant capacity. ..
- Yeh C, Chiu H, Yen G. Protective effect of sulforaphane on indomethacin-induced cytotoxicity via heme oxygenase-1 expression in human intestinal Int 407 cells. Mol Nutr Food Res. 2009;53:1166-76 pubmed publisher..Taken together, this study gives additional support to the possible use of sulforaphane as a dietary preventive agent against oxidative stress-induced intestinal injury. ..
- Lakhan S, Kirchgessner A, Hofer M. Inflammatory mechanisms in ischemic stroke: therapeutic approaches. J Transl Med. 2009;7:97 pubmed publisher..However, recent studies showing that regulatory T cells are major cerebroprotective immunomodulators after stroke suggest that targeting the endogenous adaptive immune response may offer novel promising neuroprotectant therapies. ..
- Kim K, Kang K, Zhang R, Piao M, Kim G, Kang M, et al. Up-regulation of Nrf2-mediated heme oxygenase-1 expression by eckol, a phlorotannin compound, through activation of Erk and PI3K/Akt. Int J Biochem Cell Biol. 2010;42:297-305 pubmed publisher..These studies demonstrate that eckol attenuates oxidative stress by activating Nrf2-mediated HO-1 induction via Erk and PI3K/Akt signaling. ..
- Shin D, Park H, Jung K, Choi H, Kim J, Kim D, et al. The NRF2-heme oxygenase-1 system modulates cyclosporin A-induced epithelial-mesenchymal transition and renal fibrosis. Free Radic Biol Med. 2010;48:1051-63 pubmed publisher..Collectively, our results suggest that the NRF2-HO-1 system plays a protective role against CsA-induced renal fibrosis by modulating EMT gene changes. ..
- Toledano M. The guardian recruits cops: the p53-p21 axis delegates prosurvival duties to the Keap1-Nrf2 stress pathway. Mol Cell. 2009;34:637-9 pubmed publisher..2009) report their identification of p21 as a positive regulator of Nrf2, which extends p53 prosurvival functions through recruitment of a master stress-response regulator. ..
- Calkins M, Johnson D, Townsend J, Vargas M, Dowell J, Williamson T, et al. The Nrf2/ARE pathway as a potential therapeutic target in neurodegenerative disease. Antioxid Redox Signal. 2009;11:497-508 pubmed publisher..Herein, we review the current literature that suggests that Nrf2 may be a valuable therapeutic target for neurodegenerative disease, as well as experiments that illustrate potential mechanisms of protection. ..
- Kim J, Cho H, Sir J, Kim B, Hur J, Youn S, et al. Sulfasalazine induces haem oxygenase-1 via ROS-dependent Nrf2 signalling, leading to control of neointimal hyperplasia. Cardiovasc Res. 2009;82:550-60 pubmed publisher..Our data demonstrate that SSZ inhibits VSMC proliferation in vitro and in vivo through a novel signalling pathway and may be a promising therapeutic option for the treatment of proliferative vascular disease. ..
- Oh S, Kim Y, Kim J, Kwon D, Lee E. Elevated pressure, a novel cancer therapeutic tool for sensitizing cisplatin-mediated apoptosis in A549. Biochem Biophys Res Commun. 2010;399:91-7 pubmed publisher..Collectively, these data show that administration of EP is a potential adjuvant tool for CDDP-based chemosensitivity of lung cancer cells that may reduce drug resistance. ..
- Yu A, Lu C, Wang T, Tsai C, Liu K, Cheng Y, et al. Induction of heme oxygenase 1 and inhibition of tumor necrosis factor alpha-induced intercellular adhesion molecule expression by andrographolide in EA.hy926 cells. J Agric Food Chem. 2010;58:7641-8 pubmed publisher..These results suggest that stimulation of Nrf2-dependent HO-1 expression is involved in the suppression of TNF-alpha-induced ICAM-1 expression exerted by andrographolide. ..
- Kong X, Thimmulappa R, Kombairaju P, Biswal S. NADPH oxidase-dependent reactive oxygen species mediate amplified TLR4 signaling and sepsis-induced mortality in Nrf2-deficient mice. J Immunol. 2010;185:569-77 pubmed publisher..Together, these results demonstrate that Nrf2 is essential for the regulation of NADPH oxidase-dependent ROS-mediated TLR4 activation and lethal innate immune response in sepsis. ..
- Suchocki P, Misiewicz KrzemiÅ„ska I, SkupiÅ„ska K, NiedÅºwiecka K, Lubelska K, FijaÅ‚ek Z, et al. Selenitetriglicerydes affect CYP1A1 and QR activity by involvement of reactive oxygen species and Nrf2 transcription factor. Pharmacol Rep. 2010;62:352-61 pubmed..The differential effect can be associated with the increase in Se content, leading to a change in the structure of the compound. ..
- Vargas M, Johnson J. The Nrf2-ARE cytoprotective pathway in astrocytes. Expert Rev Mol Med. 2009;11:e17 pubmed publisher..Here, we review the current data supporting Nrf2 activation in astrocytes as a viable therapeutic approach, not only in acute neuronal damage, but also in chronic neurodegeneration related to oxidative stress. ..
- Yoshikawa Y, Sasahara Y, Kitano Y, Kanazawa N, Shima H, Hashimoto Tamaoki T. Upregulation of genes orchestrating keratinocyte differentiation, including the novel marker gene ID2, by contact sensitizers in human bulge-derived keratinocytes. J Biochem Mol Toxicol. 2010;24:10-20 pubmed publisher..The use of the ID2 gene to discriminate between sensitizers and irritants might be effective as a novel marker for application during in vitro sensitization with BDKs. ..
- Wu R, Hayashi T, Cottam H, Jin G, Yao S, Wu C, et al. Nrf2 responses and the therapeutic selectivity of electrophilic compounds in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2010;107:7479-84 pubmed publisher..These experiments document the presence of Nrf2 signaling in human CLL and suggest that altered Nrf2 responses may contribute to the observed selective cytotoxicity of electrophilic compounds in this disease. ..
- Baltzer C, Tiefenböck S, Marti M, Frei C. Nutrition controls mitochondrial biogenesis in the Drosophila adipose tissue through Delg and cyclin D/Cdk4. PLoS ONE. 2009;4:e6935 pubmed publisher..These findings are the first genetic evidence that the regulation of mitochondrial mass can be uncoupled from mitochondrial activity. ..
- Kim J, Cha Y, Surh Y. A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders. Mutat Res. 2010;690:12-23 pubmed publisher..This review highlights the protective role of Nrf2 in inflammation-mediated disorders with special focus on the inflammatory signaling modulated by this redox-regulated transcription factor. ..
- Liu F, Ichihara S, Valentine W, Itoh K, Yamamoto M, Sheik Mohideen S, et al. Increased susceptibility of Nrf2-null mice to 1-bromopropane-induced hepatotoxicity. Toxicol Sci. 2010;115:596-606 pubmed publisher..That oxidative stress plays a role in 1-BP hepatotoxicity is deduced from the low expression levels and activities of antioxidant enzymes and high MDA levels in Nrf2-null mice. ..
- Rusten T, Stenmark H. p62, an autophagy hero or culprit?. Nat Cell Biol. 2010;12:207-9 pubmed publisher..Lack of autophagy leads to accumulation of p62, which is not good for liver cells, as it induces a cellular stress response that leads to disease. ..