Nitrosative/Oxidative Stress Conditions Regulate Thioredoxin-Interacting Protein (TXNIP) Expression and Thioredoxin-1 (TRX-1) Nuclear Localization
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/37088 http://dx.doi.org/10.1371/journal.pone.0084588 |
Resumo: | Thioredoxin (TRX-1) is a multifunctional protein that controls the redox status of other proteins. TRX-1 can be found in the extracellular milieu, cytoplasm and nucleus, and it has distinct functions in each environment. Previously, we studied the intracellular localization of TRX-1 and its relationship with the activation of the p21Ras - ERK1/2 MAP Kinases signaling pathway. in situations where this pathway was activated by stress conditions evoked by a nitrosothiol, S-nitroso-N-acetylpenicillamine (SNAP), TRX-1 accumulated in the nuclear compartment due to nitrosylation of p21Ras and activation of downstream ERK1/2 MAP kinases. Presently, we demonstrate that ERK1/2 MAP Kinases activation and spatial distribution within cells trigger TRX-1 nuclear translocation through downregulation of the physiological inhibitor of TRX-1, Thioredoxin Interacting Protein (TXN1P). Once activated by the oxidants, SNAP and H2O2, the ERK1/2 MAP kinases migrate to the nucleus. This is correlated with down-regulation of TXN1P. in the presence of the MEK inhibitors (PD98059 or U0126), or in cells transfected with the Protein Enriched in Astrocytes (PEA-15), a cytoplasmic anchor of ERK1/2 MAP kinases, TRX-1 nuclear migration and TXNIP down-regulation are no longer observed in cells exposed to oxidants. On the other hand, over-expression of TXNIP abolishes nuclear migration of TRX-1 under nitrosative/oxidative stress conditions, whereas gene silencing of TXNIP facilitates nuclear migration even in the absence of stress conditions. Studies based on the TXNIP promoter support this regulation. in conclusion, changes in TRX-1 compartmentalization under nitrosative/oxidative stress conditions are dependent on the expression levels of TXNIP, which are regulated by cellular compartmentalization and activation of the ERK1/2 MAP kinases. |
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Ogata, Fernando Toshio [UNIFESP]Batista, Wagner Luiz [UNIFESP]Sartori, Adriano [UNIFESP]Gesteira, Tarsis Ferreira [UNIFESP]Masutani, HiroshiArai, Roberto JunYodoi, JunjiStern, ArnoldMonteiro, Hugo Pequeno [UNIFESP]Universidade Federal de São Paulo (UNIFESP)Kyoto UnivNYUUniversidade de São Paulo (USP)2016-01-24T14:34:52Z2016-01-24T14:34:52Z2013-12-20Plos One. San Francisco: Public Library Science, v. 8, n. 12, 16 p., 2013.1932-6203http://repositorio.unifesp.br/handle/11600/37088http://dx.doi.org/10.1371/journal.pone.0084588WOS000328745100178.pdf10.1371/journal.pone.0084588WOS:000328745100178Thioredoxin (TRX-1) is a multifunctional protein that controls the redox status of other proteins. TRX-1 can be found in the extracellular milieu, cytoplasm and nucleus, and it has distinct functions in each environment. Previously, we studied the intracellular localization of TRX-1 and its relationship with the activation of the p21Ras - ERK1/2 MAP Kinases signaling pathway. in situations where this pathway was activated by stress conditions evoked by a nitrosothiol, S-nitroso-N-acetylpenicillamine (SNAP), TRX-1 accumulated in the nuclear compartment due to nitrosylation of p21Ras and activation of downstream ERK1/2 MAP kinases. Presently, we demonstrate that ERK1/2 MAP Kinases activation and spatial distribution within cells trigger TRX-1 nuclear translocation through downregulation of the physiological inhibitor of TRX-1, Thioredoxin Interacting Protein (TXN1P). Once activated by the oxidants, SNAP and H2O2, the ERK1/2 MAP kinases migrate to the nucleus. This is correlated with down-regulation of TXN1P. in the presence of the MEK inhibitors (PD98059 or U0126), or in cells transfected with the Protein Enriched in Astrocytes (PEA-15), a cytoplasmic anchor of ERK1/2 MAP kinases, TRX-1 nuclear migration and TXNIP down-regulation are no longer observed in cells exposed to oxidants. On the other hand, over-expression of TXNIP abolishes nuclear migration of TRX-1 under nitrosative/oxidative stress conditions, whereas gene silencing of TXNIP facilitates nuclear migration even in the absence of stress conditions. Studies based on the TXNIP promoter support this regulation. in conclusion, changes in TRX-1 compartmentalization under nitrosative/oxidative stress conditions are dependent on the expression levels of TXNIP, which are regulated by cellular compartmentalization and activation of the ERK1/2 MAP kinases.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Bioquim Biol Mol, São Paulo, BrazilUniversidade Federal de São Paulo, CTCMol, Ctr Cellular & Mol Therapy, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ciencias Biol, São Paulo, BrazilKyoto Univ, Dept Biol Responses, Kyoto, JapanNYU, Sch Med, Dept Pharmacol, New York, NY USAUniv São Paulo, Fac Med, Inst Canc Estado São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Bioquim Biol Mol, São Paulo, BrazilUniversidade Federal de São Paulo, CTCMol, Ctr Cellular & Mol Therapy, São Paulo, BrazilUniversidade Federal de São Paulo, ICAQF, Dept Ciencias Biol, Diadema, BrazilFAPESP: 07/59617-6FAPESP: 09/52730-7FAPESP: 12/10470-1FAPESP: 06/53791-1FAPESP: 09/50708-4Web of Science16engPublic Library SciencePlos OneNitrosative/Oxidative Stress Conditions Regulate Thioredoxin-Interacting Protein (TXNIP) Expression and Thioredoxin-1 (TRX-1) Nuclear Localizationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000328745100178.pdfapplication/pdf2137862${dspace.ui.url}/bitstream/11600/37088/1/WOS000328745100178.pdf342dd5d621459e29db34e2061ce5d551MD51open accessTEXTWOS000328745100178.pdf.txtWOS000328745100178.pdf.txtExtracted texttext/plain61484${dspace.ui.url}/bitstream/11600/37088/9/WOS000328745100178.pdf.txtfd3d91121819cdede8c245d572b56b20MD59open accessTHUMBNAILWOS000328745100178.pdf.jpgWOS000328745100178.pdf.jpgIM Thumbnailimage/jpeg7483${dspace.ui.url}/bitstream/11600/37088/11/WOS000328745100178.pdf.jpg5f92758101d8694bbc3e17fff003e136MD511open access11600/370882023-06-05 19:25:54.746open accessoai:repositorio.unifesp.br:11600/37088Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-06-05T22:25:54Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Nitrosative/Oxidative Stress Conditions Regulate Thioredoxin-Interacting Protein (TXNIP) Expression and Thioredoxin-1 (TRX-1) Nuclear Localization |
title |
Nitrosative/Oxidative Stress Conditions Regulate Thioredoxin-Interacting Protein (TXNIP) Expression and Thioredoxin-1 (TRX-1) Nuclear Localization |
spellingShingle |
Nitrosative/Oxidative Stress Conditions Regulate Thioredoxin-Interacting Protein (TXNIP) Expression and Thioredoxin-1 (TRX-1) Nuclear Localization Ogata, Fernando Toshio [UNIFESP] |
title_short |
Nitrosative/Oxidative Stress Conditions Regulate Thioredoxin-Interacting Protein (TXNIP) Expression and Thioredoxin-1 (TRX-1) Nuclear Localization |
title_full |
Nitrosative/Oxidative Stress Conditions Regulate Thioredoxin-Interacting Protein (TXNIP) Expression and Thioredoxin-1 (TRX-1) Nuclear Localization |
title_fullStr |
Nitrosative/Oxidative Stress Conditions Regulate Thioredoxin-Interacting Protein (TXNIP) Expression and Thioredoxin-1 (TRX-1) Nuclear Localization |
title_full_unstemmed |
Nitrosative/Oxidative Stress Conditions Regulate Thioredoxin-Interacting Protein (TXNIP) Expression and Thioredoxin-1 (TRX-1) Nuclear Localization |
title_sort |
Nitrosative/Oxidative Stress Conditions Regulate Thioredoxin-Interacting Protein (TXNIP) Expression and Thioredoxin-1 (TRX-1) Nuclear Localization |
author |
Ogata, Fernando Toshio [UNIFESP] |
author_facet |
Ogata, Fernando Toshio [UNIFESP] Batista, Wagner Luiz [UNIFESP] Sartori, Adriano [UNIFESP] Gesteira, Tarsis Ferreira [UNIFESP] Masutani, Hiroshi Arai, Roberto Jun Yodoi, Junji Stern, Arnold Monteiro, Hugo Pequeno [UNIFESP] |
author_role |
author |
author2 |
Batista, Wagner Luiz [UNIFESP] Sartori, Adriano [UNIFESP] Gesteira, Tarsis Ferreira [UNIFESP] Masutani, Hiroshi Arai, Roberto Jun Yodoi, Junji Stern, Arnold Monteiro, Hugo Pequeno [UNIFESP] |
author2_role |
author author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) Kyoto Univ NYU Universidade de São Paulo (USP) |
dc.contributor.author.fl_str_mv |
Ogata, Fernando Toshio [UNIFESP] Batista, Wagner Luiz [UNIFESP] Sartori, Adriano [UNIFESP] Gesteira, Tarsis Ferreira [UNIFESP] Masutani, Hiroshi Arai, Roberto Jun Yodoi, Junji Stern, Arnold Monteiro, Hugo Pequeno [UNIFESP] |
description |
Thioredoxin (TRX-1) is a multifunctional protein that controls the redox status of other proteins. TRX-1 can be found in the extracellular milieu, cytoplasm and nucleus, and it has distinct functions in each environment. Previously, we studied the intracellular localization of TRX-1 and its relationship with the activation of the p21Ras - ERK1/2 MAP Kinases signaling pathway. in situations where this pathway was activated by stress conditions evoked by a nitrosothiol, S-nitroso-N-acetylpenicillamine (SNAP), TRX-1 accumulated in the nuclear compartment due to nitrosylation of p21Ras and activation of downstream ERK1/2 MAP kinases. Presently, we demonstrate that ERK1/2 MAP Kinases activation and spatial distribution within cells trigger TRX-1 nuclear translocation through downregulation of the physiological inhibitor of TRX-1, Thioredoxin Interacting Protein (TXN1P). Once activated by the oxidants, SNAP and H2O2, the ERK1/2 MAP kinases migrate to the nucleus. This is correlated with down-regulation of TXN1P. in the presence of the MEK inhibitors (PD98059 or U0126), or in cells transfected with the Protein Enriched in Astrocytes (PEA-15), a cytoplasmic anchor of ERK1/2 MAP kinases, TRX-1 nuclear migration and TXNIP down-regulation are no longer observed in cells exposed to oxidants. On the other hand, over-expression of TXNIP abolishes nuclear migration of TRX-1 under nitrosative/oxidative stress conditions, whereas gene silencing of TXNIP facilitates nuclear migration even in the absence of stress conditions. Studies based on the TXNIP promoter support this regulation. in conclusion, changes in TRX-1 compartmentalization under nitrosative/oxidative stress conditions are dependent on the expression levels of TXNIP, which are regulated by cellular compartmentalization and activation of the ERK1/2 MAP kinases. |
publishDate |
2013 |
dc.date.issued.fl_str_mv |
2013-12-20 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:34:52Z |
dc.date.available.fl_str_mv |
2016-01-24T14:34:52Z |
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article |
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dc.identifier.citation.fl_str_mv |
Plos One. San Francisco: Public Library Science, v. 8, n. 12, 16 p., 2013. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/37088 http://dx.doi.org/10.1371/journal.pone.0084588 |
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1932-6203 |
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WOS000328745100178.pdf |
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10.1371/journal.pone.0084588 |
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WOS:000328745100178 |
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Plos One. San Francisco: Public Library Science, v. 8, n. 12, 16 p., 2013. 1932-6203 WOS000328745100178.pdf 10.1371/journal.pone.0084588 WOS:000328745100178 |
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http://repositorio.unifesp.br/handle/11600/37088 http://dx.doi.org/10.1371/journal.pone.0084588 |
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Public Library Science |
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Public Library Science |
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