Antioxidants response element

Gene regulation by tocopherols has mainly been associated with PKC because of its deactivation by a-tocopherol and its contribution in the regulation of a number of transcription factors (NF-kappaB, API). A direct participation of the pregnane X receptor (PXR)/ retinoid X receptor (RXR) has been also shown. The antioxidant-responsive element (ARE) and the TGF-beta-responsive element appear in some cases to be implicated as well. The obser ved immunmodulatory function of a-tocopherol may also be attributed to the fact that the release of the proinflammatory cytokine interlukin-l 3 can be inhibited by a-tocopherol via... 

Carotenoids have been found to exert numerous other effects of potential importance for the RPE. Carotenoids can activate transcription pathways (Ben-Dor et al., 2005 Kalariya et al., 2008 Palozza et al., 2006 Sharoni et al., 2004) for example, by activation of the antioxidant response element (ARE) (Ben-Dor et al., 2005 Sharoni et al., 2004). The ARE is an enhancer sequence responsible for the expression of many phase-II detoxification and antioxidant genes. Thus carotenoids may upregulate cellular antioxidant defenses. 

Ben-Dor, A, Steiner, M, Gheber, L, Danilenko, M, Dubi, N, Linnewiel, K, Zick, A, Sharoni, Y, and Levy, J, 2005. Carotenoids activate the antioxidant response element transcription system. Mol Cancer Ther 4, 177-186. 

It now seems that an overdose of paracetamol causes a massive chemical stress, which causes an immediate adaptive defense response in the liver cell, which senses danger via redox-sensitive transcription factors. A number of mechanisms are involved, including the release, as a result of the stress, of a transcription factor Nrf-2 from its binding with Keap 1, a cytoplasmic inhibitor. Nrf-2 translocates to the nucleus and with other activators binds to an antioxidant-response element. This leads to transcription of a number of genes, so producing a... 

Ansell PJ, Espinosa-Nicholas C, Curran EM, Judy BM, Philips BJ, Hannink M, Lubahn DB. 2004. In vitro and in vivo regulation of antioxidant response element-dependent gene expression by estrogens. Endocrinology 145 311-317. 

Kang KW, Choi SH, Kim SG. 2002. Peroxynitrite activates NF-E2-related factor 2/ antioxidant response element through the pathway of phosphatidylinositol 3-kinase The role of nitric oxide synthase in rat glutathione S-transferase A2 induction. Nitric Oxide 7 244-253. 

Nguyen T, Sherratt PJ, Pickett CB. 2003. Regulatory mechanisms controlling gene expression mediated by the antioxidant response element. Annu Rev Pharmacol Toxicol 43 233-260. 

Resveratrol induced the activity as well as the expression of NQO-1 at both protein and mRNA levels in human K562 cells by promoting nuclear translocation and subsequent binding of Nrf2 to antioxidant response element (ARE) [Hsieh et al., 2006]. The compound induced the protein and mRNA expression... 

Hsieh TC, Lu X, Wang Z, Wu JM. 2006. Induction of quinone reductase NQOl by resveratrol in human K562 cells involves the antioxidant response element ARE and is accompanied by nuclear translocation of transcription factor Nrf2. Med Chem 2 275-285. 

Balogun E, Hoque M, Gong P, Killeen E, Green CJ, Foresti R, Alam J, Motterlini R. 2003. Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element. Biochem J 371 887-895. 

Bloom D, Dhakshinamoorthy S, Jaiswal AK. 2002. Site-directed mutagenesis of cysteine to serine in the DNA binding region of Nrf2 decreases its capacity to upregulate antioxidant response element-mediated expression and antioxidant induction of NAD(P)H quinone oxidoreductasel gene. Oncogene 21 2191-2200. 

Huang HC, Nguyen T, Pickett CB. 2002. Phosphorylation of Nrf2 at Ser-40 by protein kinase C regulates antioxidant response element-mediated transcription. J Biol Chem 277 42769—42774. 

Itoh K, Wakabayashi N, Katoh Y, Ishii T, Igarashi K, Engel JD, Yamamoto M. 1999. Keapl represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev 13 76-86. 

Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, Oyake T, Hayashi N, Satoh K, Hatayama I, Yamamoto M, Nabeshima Y. 1997. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun 236 313-322. 

Katsuoka F, Motohashi H, Ishii T, Aburatani H, Engel JD, Yamamoto M. 2005. Genetic evidence that small maf proteins are essential for the activation of antioxidant response element-dependent genes. Mol Cell Biol 25 8044-8051. 

Kwak MK, Itoh K, Yamamoto M, Kensler TW. 2002. Enhanced expression of the transcription factor Nrf2 by cancer chemopreventive agents Role of antioxidant response element-like sequences in the nrf2 promoter. Mol Cell Biol 22 2883-2292. 

Nguyen T, Huang HC, Pickett CB. 2000. Transcriptional regulation of the antioxidant response element. Activation by Nrf2 and repression by MafK. J Biol Chem 275 15466-15473. 

Nguyen T, Rushmore TH, Pickett CB. 1994. Transcriptional regulation of a rat liver glutathione S-transferase Ya subunit gene. Analysis of the antioxidant response element and its activation by the phorbol ester 12-0-tetradecanoylphorbol-13-acetate. J Biol Chem 269 13656-13662. 

Nishinaka T, Ichijo Y, Ito M, Kimura M, Katsuyama M, Iwata K, Miura T, Terada T, Yabe-Nishimura C. 2007. Curcumin activates human glutathione S-transferase PI expression through antioxidant response element. Toxicol Lett 170 238-247. 

Rushmore TH, Morton MR, Pickett CB. 1991. The antioxidant responsive element. Activation by oxidative stress and identification of the DNA consensus sequence required for functional activity. J Biol Chem 266 11632-11639. 

Rushworth SA, Ogborne RM, Charalambos CA, O Connell MA. 2006. Role of protein kinase C delta in curcumin-induced antioxidant response element-mediated gene expression in human monocytes. Biochem Biophys Res Commun 341 1007-1016. 

Venugopal R, Jaiswal AK. 1996. Nrfl and Nrf2 positively and c-Fos and Fral negatively regulate the human antioxidant response element-mediated expression of NAD(P)H -quinone oxidoreductasel gene. Proc Natl Acad Sci USA 93 14960-14965. 

Wang X, Tomso DJ, Chorley BN, Cho HY, Cheung VG, Kleeberger SR, Bell DA. 2007. Identification of polymorphic antioxidant response elements in the human genome. 

Wasserman WW, Fahl WE. 1997. Functional antioxidant responsive elements. Proc Natl Acad Sci USA 94 5361-5366. 

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