Papel da ativação do fator de transcrição NRF2 na diferenciação de células SH-SY5Y mediada por Ácido Retinóico
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Tipo de documento: | Trabalho de conclusão de curso |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/122192 |
Resumo: | Retinoic acid (RA) morphogenetic properties has been used in different kinds of therapies, from neurodegenerative disorders to some types of cancer such as promyelocytic leukaemia and neuroblastoma. However, most of the pathways responsible for RA effects remain unknown. To investigate such pathways, we used a RA-induced differentiation model in the human neuroblastoma cells, SH-SY5Y. Our data showed that n-acetyl-cysteine (NAC) reduced cells proliferation rate and increased cells sensitivity to RA toxicity. Simultaneously, NAC pre-incubation attenuated NRF2 activation by RA. None of these effects were obtained with Trolox® as antioxidant, suggesting a cysteine signalization by RA. NRF2 knockdown increased cell sensibility to RA after 96 h of treatment and diminished neuroblastoma proliferation rate. Conversely, NRF2 overexpression limited RA anti-proliferative effects and increased cell proliferation. In addition, a rapid and non-genomic activation of ERK 1/2 and PI3K/AKT pathway revealed to be equally required to promote NRF2 activation and necessary to RA-induced differentiation. Together, we provide data correlating NRF2 activity with neuroblastoma proliferation and resistance to RA treatments, thus this pathway could be a potential target to optimize neuroblastoma chemotherapeutic response as well as in vitro neuronal differentiation protocols. |
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Ramos, Vitor de MirandaMoreira, Jose Claudio FonsecaZanotto Filho, Alfeu2015-08-11T02:02:21Z2015http://hdl.handle.net/10183/122192000971126Retinoic acid (RA) morphogenetic properties has been used in different kinds of therapies, from neurodegenerative disorders to some types of cancer such as promyelocytic leukaemia and neuroblastoma. However, most of the pathways responsible for RA effects remain unknown. To investigate such pathways, we used a RA-induced differentiation model in the human neuroblastoma cells, SH-SY5Y. Our data showed that n-acetyl-cysteine (NAC) reduced cells proliferation rate and increased cells sensitivity to RA toxicity. Simultaneously, NAC pre-incubation attenuated NRF2 activation by RA. None of these effects were obtained with Trolox® as antioxidant, suggesting a cysteine signalization by RA. NRF2 knockdown increased cell sensibility to RA after 96 h of treatment and diminished neuroblastoma proliferation rate. Conversely, NRF2 overexpression limited RA anti-proliferative effects and increased cell proliferation. In addition, a rapid and non-genomic activation of ERK 1/2 and PI3K/AKT pathway revealed to be equally required to promote NRF2 activation and necessary to RA-induced differentiation. Together, we provide data correlating NRF2 activity with neuroblastoma proliferation and resistance to RA treatments, thus this pathway could be a potential target to optimize neuroblastoma chemotherapeutic response as well as in vitro neuronal differentiation protocols.application/pdfengÁcido retinóicoNeuroblastomaFator 2 relacionado a NF-E2Papel da ativação do fator de transcrição NRF2 na diferenciação de células SH-SY5Y mediada por Ácido RetinóicoThe role of Nrf2 activation in human neuroblastoma cells treated with retinoic acid info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/bachelorThesisUniversidade Federal do Rio Grande do SulInstituto de BiociênciasPorto Alegre, BR-RS2015Ciências Biológicas: Bachareladograduaçãoinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSORIGINAL000971126.pdf000971126.pdfTexto completo (inglês)application/pdf1559751http://www.lume.ufrgs.br/bitstream/10183/122192/1/000971126.pdfa2ffff1604f53ff77ab070d3ee6be131MD51TEXT000971126.pdf.txt000971126.pdf.txtExtracted Texttext/plain45074http://www.lume.ufrgs.br/bitstream/10183/122192/2/000971126.pdf.txt35e8902bbf5bc3c8a5cd628bc8ba4c97MD52THUMBNAIL000971126.pdf.jpg000971126.pdf.jpgGenerated Thumbnailimage/jpeg1449http://www.lume.ufrgs.br/bitstream/10183/122192/3/000971126.pdf.jpg0843c6eb014069b675dfbc9e6d7ea854MD5310183/1221922021-05-07 05:10:07.82521oai:www.lume.ufrgs.br:10183/122192Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2021-05-07T08:10:07Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Papel da ativação do fator de transcrição NRF2 na diferenciação de células SH-SY5Y mediada por Ácido Retinóico |
dc.title.alternative.en.fl_str_mv |
The role of Nrf2 activation in human neuroblastoma cells treated with retinoic acid |
title |
Papel da ativação do fator de transcrição NRF2 na diferenciação de células SH-SY5Y mediada por Ácido Retinóico |
spellingShingle |
Papel da ativação do fator de transcrição NRF2 na diferenciação de células SH-SY5Y mediada por Ácido Retinóico Ramos, Vitor de Miranda Ácido retinóico Neuroblastoma Fator 2 relacionado a NF-E2 |
title_short |
Papel da ativação do fator de transcrição NRF2 na diferenciação de células SH-SY5Y mediada por Ácido Retinóico |
title_full |
Papel da ativação do fator de transcrição NRF2 na diferenciação de células SH-SY5Y mediada por Ácido Retinóico |
title_fullStr |
Papel da ativação do fator de transcrição NRF2 na diferenciação de células SH-SY5Y mediada por Ácido Retinóico |
title_full_unstemmed |
Papel da ativação do fator de transcrição NRF2 na diferenciação de células SH-SY5Y mediada por Ácido Retinóico |
title_sort |
Papel da ativação do fator de transcrição NRF2 na diferenciação de células SH-SY5Y mediada por Ácido Retinóico |
author |
Ramos, Vitor de Miranda |
author_facet |
Ramos, Vitor de Miranda |
author_role |
author |
dc.contributor.author.fl_str_mv |
Ramos, Vitor de Miranda |
dc.contributor.advisor1.fl_str_mv |
Moreira, Jose Claudio Fonseca |
dc.contributor.advisor-co1.fl_str_mv |
Zanotto Filho, Alfeu |
contributor_str_mv |
Moreira, Jose Claudio Fonseca Zanotto Filho, Alfeu |
dc.subject.por.fl_str_mv |
Ácido retinóico Neuroblastoma Fator 2 relacionado a NF-E2 |
topic |
Ácido retinóico Neuroblastoma Fator 2 relacionado a NF-E2 |
description |
Retinoic acid (RA) morphogenetic properties has been used in different kinds of therapies, from neurodegenerative disorders to some types of cancer such as promyelocytic leukaemia and neuroblastoma. However, most of the pathways responsible for RA effects remain unknown. To investigate such pathways, we used a RA-induced differentiation model in the human neuroblastoma cells, SH-SY5Y. Our data showed that n-acetyl-cysteine (NAC) reduced cells proliferation rate and increased cells sensitivity to RA toxicity. Simultaneously, NAC pre-incubation attenuated NRF2 activation by RA. None of these effects were obtained with Trolox® as antioxidant, suggesting a cysteine signalization by RA. NRF2 knockdown increased cell sensibility to RA after 96 h of treatment and diminished neuroblastoma proliferation rate. Conversely, NRF2 overexpression limited RA anti-proliferative effects and increased cell proliferation. In addition, a rapid and non-genomic activation of ERK 1/2 and PI3K/AKT pathway revealed to be equally required to promote NRF2 activation and necessary to RA-induced differentiation. Together, we provide data correlating NRF2 activity with neuroblastoma proliferation and resistance to RA treatments, thus this pathway could be a potential target to optimize neuroblastoma chemotherapeutic response as well as in vitro neuronal differentiation protocols. |
publishDate |
2015 |
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2015 |
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