title: Thioredoxin-dependent redox regulation of the antioxidant responsive element (ARE) in electrophile response.
abstract: Thioredoxin is a redox-regulating protein, the expression of which is induced by various forms of oxidative stress. Thioredoxin controls the interactions of various transcription factors through redox regulation. In K562 cells, we have previously reported that hemin induces activation of the thioredoxin gene by regulating NF-E2-related factor (Nrf2) through the antioxidant responsive element (ARE). We showed here that tert-butylhydroquinone (tBHQ), an electrophile stressor, activates the thioredoxin gene through the ARE. In an electrophoretic mobility shift assay, a specific Nrf2/small Maf binding complex was induced by tBHQ and bound to the ARE. Overexpression of Nrf2 increased the tBHQ-induced thioredoxin gene activation through the ARE, whereas that of Jun and Fos suppressed the activation. The tBHQ-induced ARE binding activity was completely abrogated by an oxidizing agent, diamide, whereas 2-mercaptoethanol (2-ME) reversibly recovered the inhibitory effects of diamide, suggesting that ARE binding activity is redox-dependent. Moreover, overexpression of thioredoxin enhanced the ARE-mediated thioredoxin gene activation by tBHQ. Therefore, ARE-mediated induction of thioredoxin expression is a mechanism of enhancing signal transduction through the ARE in electrophile-induced stress responses.
authors.affiliation: Department of Biological Responses, Institute for Virus Research, Kyoto University, Japan.
authors.forename: Yong-Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Norihiko
authors.initials: N
authors.lastname: Kondo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Masutani
authors.forename: Junji
authors.initials: J
authors.lastname: Yodoi
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology; D020014:K562 Cells; D050985:MafK Transcription Factor; D051267:NF-E2-Related Factor 2; D009687:Nuclear Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D011401:Promoter Regions, Genetic; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004268:DNA-Binding Proteins; D006873:Hydroquinones; D050985:MafK Transcription Factor; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D009687:Nuclear Proteins; D015534:Trans-Activators; D013879:Thioredoxins; C018855:2-tert-butylhydroquinone