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dc.contributor.advisorMoreira, Jose Claudio Fonsecapt_BR
dc.contributor.authorRamos, Vitor de Mirandapt_BR
dc.date.accessioned2015-08-11T02:02:21Zpt_BR
dc.date.issued2015pt_BR
dc.identifier.urihttp://hdl.handle.net/10183/122192pt_BR
dc.description.abstractRetinoic 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.en
dc.format.mimetypeapplication/pdfpt_BR
dc.language.isoengpt_BR
dc.rightsOpen Accessen
dc.subjectÁcido retinóicopt_BR
dc.subjectNeuroblastomapt_BR
dc.subjectFator 2 relacionado a NF-E2pt_BR
dc.titlePapel da ativação do fator de transcrição NRF2 na diferenciação de células SH-SY5Y mediada por Ácido Retinóicopt_BR
dc.title.alternativeThe role of Nrf2 activation in human neuroblastoma cells treated with retinoic acid en
dc.typeTrabalho de conclusão de graduaçãopt_BR
dc.contributor.advisor-coZanotto Filho, Alfeupt_BR
dc.identifier.nrb000971126pt_BR
dc.degree.grantorUniversidade Federal do Rio Grande do Sulpt_BR
dc.degree.departmentInstituto de Biociênciaspt_BR
dc.degree.localPorto Alegre, BR-RSpt_BR
dc.degree.date2015pt_BR
dc.degree.graduationCiências Biológicas: Bachareladopt_BR
dc.degree.levelgraduaçãopt_BR


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