Aspirin metabolite sodium salicylate selectively inhibits transcriptional activity of ATF6α and downstream target genes
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | http://hdl.handle.net/1843/61416 |
Resumo: | In response to ER stress, activating transcription factor 6 (ATF6) traffics from ER to Golgi apparatus where it is activated by cleavage before being translocated as transcription factor to the cell nucleus. In this work we describe ATF6α as a newly target of the aspirin metabolite sodium salicylate (NaSal). NaSal treatment of cells induces increases in ATF6α mRNA and protein levels, but these events are not accompanied by ATF6 activation. Conversely, NaSal inhibited ATF6 transactivating activity elicited by various ER stress-inducing stimuli in different cell types. This resulted in reduced expression of a subset of ATF6α target genes. Mechanistically, exposure of cells to NaSal results in ATF6α trapping at the Golgi apparatus, thus preventing nuclear translocation. This study provides evidence that NaSal compound restrains the activity of ATF6α, thereby preventing activation of a specific subset of ER-stress responsive genes implicated in different cellular responses. |
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2023-11-27T19:57:31Z2023-11-27T19:57:31Z2017711210.1038/s41598-017-09500-x2045-2322http://hdl.handle.net/1843/61416In response to ER stress, activating transcription factor 6 (ATF6) traffics from ER to Golgi apparatus where it is activated by cleavage before being translocated as transcription factor to the cell nucleus. In this work we describe ATF6α as a newly target of the aspirin metabolite sodium salicylate (NaSal). NaSal treatment of cells induces increases in ATF6α mRNA and protein levels, but these events are not accompanied by ATF6 activation. Conversely, NaSal inhibited ATF6 transactivating activity elicited by various ER stress-inducing stimuli in different cell types. This resulted in reduced expression of a subset of ATF6α target genes. Mechanistically, exposure of cells to NaSal results in ATF6α trapping at the Golgi apparatus, thus preventing nuclear translocation. This study provides evidence that NaSal compound restrains the activity of ATF6α, thereby preventing activation of a specific subset of ER-stress responsive genes implicated in different cellular responses.Em resposta ao estresse do RE, a ativação do fator de transcrição 6 (ATF6) trafega do RE para o aparelho de Golgi, onde é ativado por clivagem antes de ser translocado como fator de transcrição para o núcleo da célula. Neste trabalho descrevemos o ATF6α como um novo alvo do metabólito da aspirina salicilato de sódio (NaSal). O tratamento de células com NaSal induz aumentos nos níveis de mRNA e proteína do ATF6α, mas esses eventos não são acompanhados pela ativação do ATF6. Por outro lado, o NaSal inibiu a atividade transativadora do ATF6 provocada por vários estímulos indutores de estresse de ER em diferentes tipos de células. Isto resultou na redução da expressão de um subconjunto de genes alvo ATF6α. Mecanisticamente, a exposição das células ao NaSal resulta no aprisionamento do ATF6α no aparelho de Golgi, evitando assim a translocação nuclear. Este estudo fornece evidências de que o composto NaSal restringe a atividade do ATF6α, evitando assim a ativação de um subconjunto específico de genes responsivos ao estresse do ER implicados em diferentes respostas celulares.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas GeraisCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorengUniversidade Federal de Minas GeraisUFMGBrasilICB - DEPARTAMENTO DE MORFOLOGIAscientific reportsFatores de transcriçãoSalicilato de sódioTranslocação nuclearNúcleo celularGolgi, aparelho deTranscription factorSodium salicylateNuclear translocationCell nucleusGolgi apparatusAspirin metabolite sodium salicylate selectively inhibits transcriptional activity of ATF6α and downstream target genesO salicilato de sódio do metabólito da aspirina inibe seletivamente a atividade transcricional de ATF6α e genes alvo a jusanteinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://www.nature.com/articles/s41598-017-09500-xFernanda Lins Brandão MüggeAristóbolo Mendes da Silvainfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/61416/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALAspirin metabolite sodium salicylate selectively inhibits transcriptional activity of ATF6 and downstream target genes.pdfAspirin metabolite sodium salicylate selectively inhibits transcriptional activity of ATF6 and downstream target genes.pdfapplication/pdf1773955https://repositorio.ufmg.br/bitstream/1843/61416/2/Aspirin%20metabolite%20sodium%20salicylate%20selectively%20inhibits%20transcriptional%20activity%20of%20ATF6%20and%20downstream%20target%20genes.pdf7d6d300508dbacd8d5b6ef9485e01946MD521843/614162023-11-27 18:23:33.987oai:repositorio.ufmg.br:1843/61416TElDRU7vv71BIERFIERJU1RSSUJVSe+/ve+/vU8gTu+/vU8tRVhDTFVTSVZBIERPIFJFUE9TSVTvv71SSU8gSU5TVElUVUNJT05BTCBEQSBVRk1HCiAKCkNvbSBhIGFwcmVzZW50Ye+/ve+/vW8gZGVzdGEgbGljZW7vv71hLCB2b2Pvv70gKG8gYXV0b3IgKGVzKSBvdSBvIHRpdHVsYXIgZG9zIGRpcmVpdG9zIGRlIGF1dG9yKSBjb25jZWRlIGFvIFJlcG9zaXTvv71yaW8gSW5zdGl0dWNpb25hbCBkYSBVRk1HIChSSS1VRk1HKSBvIGRpcmVpdG8gbu+/vW8gZXhjbHVzaXZvIGUgaXJyZXZvZ++/vXZlbCBkZSByZXByb2R1emlyIGUvb3UgZGlzdHJpYnVpciBhIHN1YSBwdWJsaWNh77+977+9byAoaW5jbHVpbmRvIG8gcmVzdW1vKSBwb3IgdG9kbyBvIG11bmRvIG5vIGZvcm1hdG8gaW1wcmVzc28gZSBlbGV0cu+/vW5pY28gZSBlbSBxdWFscXVlciBtZWlvLCBpbmNsdWluZG8gb3MgZm9ybWF0b3Mg77+9dWRpbyBvdSB277+9ZGVvLgoKVm9j77+9IGRlY2xhcmEgcXVlIGNvbmhlY2UgYSBwb2zvv710aWNhIGRlIGNvcHlyaWdodCBkYSBlZGl0b3JhIGRvIHNldSBkb2N1bWVudG8gZSBxdWUgY29uaGVjZSBlIGFjZWl0YSBhcyBEaXJldHJpemVzIGRvIFJJLVVGTUcuCgpWb2Pvv70gY29uY29yZGEgcXVlIG8gUmVwb3NpdO+/vXJpbyBJbnN0aXR1Y2lvbmFsIGRhIFVGTUcgcG9kZSwgc2VtIGFsdGVyYXIgbyBjb250Ze+/vWRvLCB0cmFuc3BvciBhIHN1YSBwdWJsaWNh77+977+9byBwYXJhIHF1YWxxdWVyIG1laW8gb3UgZm9ybWF0byBwYXJhIGZpbnMgZGUgcHJlc2VydmHvv73vv71vLgoKVm9j77+9IHRhbWLvv71tIGNvbmNvcmRhIHF1ZSBvIFJlcG9zaXTvv71yaW8gSW5zdGl0dWNpb25hbCBkYSBVRk1HIHBvZGUgbWFudGVyIG1haXMgZGUgdW1hIGPvv71waWEgZGUgc3VhIHB1YmxpY2Hvv73vv71vIHBhcmEgZmlucyBkZSBzZWd1cmFu77+9YSwgYmFjay11cCBlIHByZXNlcnZh77+977+9by4KClZvY++/vSBkZWNsYXJhIHF1ZSBhIHN1YSBwdWJsaWNh77+977+9byDvv70gb3JpZ2luYWwgZSBxdWUgdm9j77+9IHRlbSBvIHBvZGVyIGRlIGNvbmNlZGVyIG9zIGRpcmVpdG9zIGNvbnRpZG9zIG5lc3RhIGxpY2Vu77+9YS4gVm9j77+9IHRhbWLvv71tIGRlY2xhcmEgcXVlIG8gZGVw77+9c2l0byBkZSBzdWEgcHVibGljYe+/ve+/vW8gbu+/vW8sIHF1ZSBzZWphIGRlIHNldSBjb25oZWNpbWVudG8sIGluZnJpbmdlIGRpcmVpdG9zIGF1dG9yYWlzIGRlIG5pbmd177+9bS4KCkNhc28gYSBzdWEgcHVibGljYe+/ve+/vW8gY29udGVuaGEgbWF0ZXJpYWwgcXVlIHZvY++/vSBu77+9byBwb3NzdWkgYSB0aXR1bGFyaWRhZGUgZG9zIGRpcmVpdG9zIGF1dG9yYWlzLCB2b2Pvv70gZGVjbGFyYSBxdWUgb2J0ZXZlIGEgcGVybWlzc++/vW8gaXJyZXN0cml0YSBkbyBkZXRlbnRvciBkb3MgZGlyZWl0b3MgYXV0b3JhaXMgcGFyYSBjb25jZWRlciBhbyBSZXBvc2l077+9cmlvIEluc3RpdHVjaW9uYWwgZGEgVUZNRyBvcyBkaXJlaXRvcyBhcHJlc2VudGFkb3MgbmVzdGEgbGljZW7vv71hLCBlIHF1ZSBlc3NlIG1hdGVyaWFsIGRlIHByb3ByaWVkYWRlIGRlIHRlcmNlaXJvcyBlc3Tvv70gY2xhcmFtZW50ZSBpZGVudGlmaWNhZG8gZSByZWNvbmhlY2lkbyBubyB0ZXh0byBvdSBubyBjb250Ze+/vWRvIGRhIHB1YmxpY2Hvv73vv71vIG9yYSBkZXBvc2l0YWRhLgoKQ0FTTyBBIFBVQkxJQ0Hvv73vv71PIE9SQSBERVBPU0lUQURBIFRFTkhBIFNJRE8gUkVTVUxUQURPIERFIFVNIFBBVFJPQ++/vU5JTyBPVSBBUE9JTyBERSBVTUEgQUfvv71OQ0lBIERFIEZPTUVOVE8gT1UgT1VUUk8gT1JHQU5JU01PLCBWT0Pvv70gREVDTEFSQSBRVUUgUkVTUEVJVE9VIFRPRE9TIEUgUVVBSVNRVUVSIERJUkVJVE9TIERFIFJFVklT77+9TyBDT01PIFRBTULvv71NIEFTIERFTUFJUyBPQlJJR0Hvv73vv71FUyBFWElHSURBUyBQT1IgQ09OVFJBVE8gT1UgQUNPUkRPLgoKTyBSZXBvc2l077+9cmlvIEluc3RpdHVjaW9uYWwgZGEgVUZNRyBzZSBjb21wcm9tZXRlIGEgaWRlbnRpZmljYXIgY2xhcmFtZW50ZSBvIHNldSBub21lKHMpIG91IG8ocykgbm9tZXMocykgZG8ocykgZGV0ZW50b3IoZXMpIGRvcyBkaXJlaXRvcyBhdXRvcmFpcyBkYSBwdWJsaWNh77+977+9bywgZSBu77+9byBmYXLvv70gcXVhbHF1ZXIgYWx0ZXJh77+977+9bywgYWzvv71tIGRhcXVlbGFzIGNvbmNlZGlkYXMgcG9yIGVzdGEgbGljZW7vv71hLgo=Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-11-27T21:23:33Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
dc.title.pt_BR.fl_str_mv |
Aspirin metabolite sodium salicylate selectively inhibits transcriptional activity of ATF6α and downstream target genes |
dc.title.alternative.pt_BR.fl_str_mv |
O salicilato de sódio do metabólito da aspirina inibe seletivamente a atividade transcricional de ATF6α e genes alvo a jusante |
title |
Aspirin metabolite sodium salicylate selectively inhibits transcriptional activity of ATF6α and downstream target genes |
spellingShingle |
Aspirin metabolite sodium salicylate selectively inhibits transcriptional activity of ATF6α and downstream target genes Fernanda Lins Brandão Mügge Transcription factor Sodium salicylate Nuclear translocation Cell nucleus Golgi apparatus Fatores de transcrição Salicilato de sódio Translocação nuclear Núcleo celular Golgi, aparelho de |
title_short |
Aspirin metabolite sodium salicylate selectively inhibits transcriptional activity of ATF6α and downstream target genes |
title_full |
Aspirin metabolite sodium salicylate selectively inhibits transcriptional activity of ATF6α and downstream target genes |
title_fullStr |
Aspirin metabolite sodium salicylate selectively inhibits transcriptional activity of ATF6α and downstream target genes |
title_full_unstemmed |
Aspirin metabolite sodium salicylate selectively inhibits transcriptional activity of ATF6α and downstream target genes |
title_sort |
Aspirin metabolite sodium salicylate selectively inhibits transcriptional activity of ATF6α and downstream target genes |
author |
Fernanda Lins Brandão Mügge |
author_facet |
Fernanda Lins Brandão Mügge Aristóbolo Mendes da Silva |
author_role |
author |
author2 |
Aristóbolo Mendes da Silva |
author2_role |
author |
dc.contributor.author.fl_str_mv |
Fernanda Lins Brandão Mügge Aristóbolo Mendes da Silva |
dc.subject.por.fl_str_mv |
Transcription factor Sodium salicylate Nuclear translocation Cell nucleus Golgi apparatus |
topic |
Transcription factor Sodium salicylate Nuclear translocation Cell nucleus Golgi apparatus Fatores de transcrição Salicilato de sódio Translocação nuclear Núcleo celular Golgi, aparelho de |
dc.subject.other.pt_BR.fl_str_mv |
Fatores de transcrição Salicilato de sódio Translocação nuclear Núcleo celular Golgi, aparelho de |
description |
In response to ER stress, activating transcription factor 6 (ATF6) traffics from ER to Golgi apparatus where it is activated by cleavage before being translocated as transcription factor to the cell nucleus. In this work we describe ATF6α as a newly target of the aspirin metabolite sodium salicylate (NaSal). NaSal treatment of cells induces increases in ATF6α mRNA and protein levels, but these events are not accompanied by ATF6 activation. Conversely, NaSal inhibited ATF6 transactivating activity elicited by various ER stress-inducing stimuli in different cell types. This resulted in reduced expression of a subset of ATF6α target genes. Mechanistically, exposure of cells to NaSal results in ATF6α trapping at the Golgi apparatus, thus preventing nuclear translocation. This study provides evidence that NaSal compound restrains the activity of ATF6α, thereby preventing activation of a specific subset of ER-stress responsive genes implicated in different cellular responses. |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017 |
dc.date.accessioned.fl_str_mv |
2023-11-27T19:57:31Z |
dc.date.available.fl_str_mv |
2023-11-27T19:57:31Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1843/61416 |
dc.identifier.doi.pt_BR.fl_str_mv |
10.1038/s41598-017-09500-x |
dc.identifier.issn.pt_BR.fl_str_mv |
2045-2322 |
identifier_str_mv |
10.1038/s41598-017-09500-x 2045-2322 |
url |
http://hdl.handle.net/1843/61416 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
scientific reports |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais |
dc.publisher.initials.fl_str_mv |
UFMG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
ICB - DEPARTAMENTO DE MORFOLOGIA |
publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFMG instname:Universidade Federal de Minas Gerais (UFMG) instacron:UFMG |
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UFMG |
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UFMG |
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Repositório Institucional da UFMG |
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Repositório Institucional da UFMG |
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