
DOI . ORG {
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Title[redir]:
Thioredoxin-dependent redox regulation of the antioxidant responsive element (ARE) in electrophile response | Oncogene
Description:
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.
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Keywords {🔍}
nature, article, access, research, thioredoxin, biol, content, oncogene, yodoi, itoh, yamamoto, cookies, masutani, stress, privacy, redox, regulation, antioxidant, kim, oxidative, activation, sci, cell, japan, data, responsive, element, electrophile, yamaguchi, hiroshi, gene, nrf, tbhq, open, science, proc, natl, acad, usa, igarashi, mol, chem, advertising, information, journal, subscribe, march, yongchul, kondo, junji,
Topics {✒️}
nature portfolio scientific research permissions reprints privacy policy nature regulating nf-e2-related factor advertising social media junior research fellowship author information authors hiroshi masutani & junji yodoi author correspondence research fellowship development program virus research electrophile-induced stress responses personal data thioredoxin-dependent redox regulation nfe2l2/ap-1 targets expression springerlink instant access research data protection pyn3215/c-fos vectors permissions anti-mafk antibodies yong-chul kim antioxidant responsive element japan society examination stress petr privacy redox-regulating protein enhancing signal transduction issue learn providing pef-nrf2 pef-mafk vectors explore content subscription content redox regulation electrophile european economic area institutional subscriptions read potent tyrosinase inhibitors rauscher iii fj bio-industry initiatives sprague–dawley rats nfe2l2/ap1 pathway accepting optional cookies hemin induces activation article kim hiroshi masutani japan
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headline:Thioredoxin-dependent redox regulation of the antioxidant responsive element (ARE) in electrophile response
description: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.
datePublished:2003-03-27T00:00:00Z
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description: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.
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