Alteração da expressão de genes relacionados a doenças neurodegenerativas em modelos inflamatórios tratados com inibidores de APE1

Detalhes bibliográficos
Autor(a) principal: Oliveira, Thais Teixeira
Data de Publicação: 2017
Tipo de documento: Trabalho de conclusão de curso
Idioma: por
Título da fonte: Repositório Institucional da UFRN
Texto Completo: https://repositorio.ufrn.br/handle/123456789/43174
Resumo: Inflammation is one of the main defense mechanisms against pathogens and antigens, but in the nervous system inflammation can lead to functional disturbance and death of neurons when it develops in a chronic or exacerbated way. Infectious diseases, such as meningitidis, which develop in the CNS often cause complications and neuronal death, many studies have already associated these complications with reactive oxygen species generated during inflammation. Due to the damage caused to DNA and its relation to neuronal death, our research group investigated the relationship of DNA repair enzymes with the occurrence of bacterial meningitis, in this study we observed that the occurrence of polymorphisms in genes of the bases excision repair was more frequent in patients with bacterial meningitis, in addition the amount of DNA damage was also higher in patients with APE1 and OGG1 polymorphism. To investigate the anti-inflammatory role of APE1, we performed a sequencing of the monocyte lineage RNA pool (U937) by observing gene expression alterations after the use of E3330 inhibitors Methoxyamine and resveratrol, one of the results was the appearance of many Genes belonging to neurodegeneration pathways with altered expression after the treatments. This work aimed to investigate these genes better; we observed that the treatment with E3330 and Resveratrol down regulates many mitochondrial genes involved in the pathogenesis of diseases such as Parkinson and Alzheimer.
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spelling Oliveira, Thais TeixeiraLajus, Tirzah Braz PettaLima, Lucymara Fassarella Agnez2018-04-03T13:55:50Z2021-10-06T11:14:59Z2018-04-03T13:55:50Z2021-10-06T11:14:59Z20172012912160OLIVEIRA, Thais Teixeira. Alteração da expressão de genes relacionados a doenças neurodegenerativas em modelos inflamatórios tratados com inibidores de APE1. 2017. 79 f. Trabalho de Conclusão de Curso (Graduação em Biomedicina) - Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal-RN, 2017.https://repositorio.ufrn.br/handle/123456789/43174Inflammation is one of the main defense mechanisms against pathogens and antigens, but in the nervous system inflammation can lead to functional disturbance and death of neurons when it develops in a chronic or exacerbated way. Infectious diseases, such as meningitidis, which develop in the CNS often cause complications and neuronal death, many studies have already associated these complications with reactive oxygen species generated during inflammation. Due to the damage caused to DNA and its relation to neuronal death, our research group investigated the relationship of DNA repair enzymes with the occurrence of bacterial meningitis, in this study we observed that the occurrence of polymorphisms in genes of the bases excision repair was more frequent in patients with bacterial meningitis, in addition the amount of DNA damage was also higher in patients with APE1 and OGG1 polymorphism. To investigate the anti-inflammatory role of APE1, we performed a sequencing of the monocyte lineage RNA pool (U937) by observing gene expression alterations after the use of E3330 inhibitors Methoxyamine and resveratrol, one of the results was the appearance of many Genes belonging to neurodegeneration pathways with altered expression after the treatments. This work aimed to investigate these genes better; we observed that the treatment with E3330 and Resveratrol down regulates many mitochondrial genes involved in the pathogenesis of diseases such as Parkinson and Alzheimer.A inflamação no sistema nervoso pode levar a perturbação funcional e morte de neurônios quando se desenvolve de maneira crônica ou exacerbada, doenças de base infecciosa como Meningite, frequentemente causam complicações, associadas a espécies reativas de oxigênio (ERO) geradas durante a inflamação. Devido aos danos causados ao DNA por ERO e sua relação com a morte neuronal, o papel das vias de reparo de DNA e suas consequências durante processos inflamatórios vem sendo estudado. Nosso grupo observou que a ocorrência de polimorfismos em genes da via de reparo por excisão de bases, foi mais frequente em pacientes com meningite bacteriana, foram observados aumento na ocorrência de danos no DNA, redução dos níveis de citocinas e desbalanço na produção de anticorpos nesses pacientes. Visando investigar melhor o papel da enzima APE1 durante o processo inflamatório, nosso grupo estabeleceu um modelo de inflamação in vitro, utilizando linhagem de monócitos (U937) tratadas com lipopolissacarídeo (LPS) e posterior adição de inibidores específicos para funções da enzima APE1, E3330 e metoxiamina, e do antioxidante resveratrol. A partir desse modelo, foram obtidos os transcriptomas dos diferentes tratamentos. Dentre os genes diferencialmente expressos foram identificados vários genes envolvidos em vias de neurodegeneração. Foi observado que o tratamento com E3330 e resveratrol leva a redução de expressão de muitos genes mitocondriais envolvidos com a patogênese de doenças como Parkinson e Alzheimer.CNPqUniversidade Federal do Rio Grande do NorteUFRNBrasilBiomedicinaEstresse oxidativoOxidative stressNeurodegeneraçãoNeurodegenerationMitocondriaMitochondriaAlteração da expressão de genes relacionados a doenças neurodegenerativas em modelos inflamatórios tratados com inibidores de APE1info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/bachelorThesisinfo:eu-repo/semantics/embargoedAccessporreponame:Repositório Institucional da UFRNinstname:Universidade Federal do Rio Grande do Norte (UFRN)instacron:UFRNTEXTExpressaoGenes_Oliveira_2017.pdf.txtExtracted texttext/plain123679https://repositorio.ufrn.br/bitstream/123456789/43174/1/ExpressaoGenes_Oliveira_2017.pdf.txt033709a02c9919bae8d6d1f696486dafMD51AlteracaoExpressaoGenes_Oliveira_2017.pdf.txtExtracted texttext/plain123679https://repositorio.ufrn.br/bitstream/123456789/43174/2/AlteracaoExpressaoGenes_Oliveira_2017.pdf.txt033709a02c9919bae8d6d1f696486dafMD52ORIGINALAlteracaoExpressaoGenes_Oliveira_2017.pdfMonografiaapplication/pdf2982625https://repositorio.ufrn.br/bitstream/123456789/43174/3/AlteracaoExpressaoGenes_Oliveira_2017.pdf4a97a82188dd1b6ef8e3ce2dd01d0201MD53CC-LICENSElicense_urlapplication/octet-stream49https://repositorio.ufrn.br/bitstream/123456789/43174/4/license_url4afdbb8c545fd630ea7db775da747b2fMD54license_textapplication/octet-stream0https://repositorio.ufrn.br/bitstream/123456789/43174/5/license_textd41d8cd98f00b204e9800998ecf8427eMD55license_rdfapplication/octet-stream0https://repositorio.ufrn.br/bitstream/123456789/43174/6/license_rdfd41d8cd98f00b204e9800998ecf8427eMD56LICENSElicense.txttext/plain756https://repositorio.ufrn.br/bitstream/123456789/43174/7/license.txta80a9cda2756d355b388cc443c3d8a43MD57123456789/431742021-10-06 08:14:59.983oai:https://repositorio.ufrn.br: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ório de PublicaçõesPUBhttp://repositorio.ufrn.br/oai/opendoar:2021-10-06T11:14:59Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN)false
dc.title.pr_BR.fl_str_mv Alteração da expressão de genes relacionados a doenças neurodegenerativas em modelos inflamatórios tratados com inibidores de APE1
title Alteração da expressão de genes relacionados a doenças neurodegenerativas em modelos inflamatórios tratados com inibidores de APE1
spellingShingle Alteração da expressão de genes relacionados a doenças neurodegenerativas em modelos inflamatórios tratados com inibidores de APE1
Oliveira, Thais Teixeira
Estresse oxidativo
Oxidative stress
Neurodegeneração
Neurodegeneration
Mitocondria
Mitochondria
title_short Alteração da expressão de genes relacionados a doenças neurodegenerativas em modelos inflamatórios tratados com inibidores de APE1
title_full Alteração da expressão de genes relacionados a doenças neurodegenerativas em modelos inflamatórios tratados com inibidores de APE1
title_fullStr Alteração da expressão de genes relacionados a doenças neurodegenerativas em modelos inflamatórios tratados com inibidores de APE1
title_full_unstemmed Alteração da expressão de genes relacionados a doenças neurodegenerativas em modelos inflamatórios tratados com inibidores de APE1
title_sort Alteração da expressão de genes relacionados a doenças neurodegenerativas em modelos inflamatórios tratados com inibidores de APE1
author Oliveira, Thais Teixeira
author_facet Oliveira, Thais Teixeira
author_role author
dc.contributor.referees1.none.fl_str_mv Lajus, Tirzah Braz Petta
dc.contributor.author.fl_str_mv Oliveira, Thais Teixeira
dc.contributor.advisor1.fl_str_mv Lima, Lucymara Fassarella Agnez
contributor_str_mv Lima, Lucymara Fassarella Agnez
dc.subject.pr_BR.fl_str_mv Estresse oxidativo
Oxidative stress
Neurodegeneração
Neurodegeneration
Mitocondria
Mitochondria
topic Estresse oxidativo
Oxidative stress
Neurodegeneração
Neurodegeneration
Mitocondria
Mitochondria
description Inflammation is one of the main defense mechanisms against pathogens and antigens, but in the nervous system inflammation can lead to functional disturbance and death of neurons when it develops in a chronic or exacerbated way. Infectious diseases, such as meningitidis, which develop in the CNS often cause complications and neuronal death, many studies have already associated these complications with reactive oxygen species generated during inflammation. Due to the damage caused to DNA and its relation to neuronal death, our research group investigated the relationship of DNA repair enzymes with the occurrence of bacterial meningitis, in this study we observed that the occurrence of polymorphisms in genes of the bases excision repair was more frequent in patients with bacterial meningitis, in addition the amount of DNA damage was also higher in patients with APE1 and OGG1 polymorphism. To investigate the anti-inflammatory role of APE1, we performed a sequencing of the monocyte lineage RNA pool (U937) by observing gene expression alterations after the use of E3330 inhibitors Methoxyamine and resveratrol, one of the results was the appearance of many Genes belonging to neurodegeneration pathways with altered expression after the treatments. This work aimed to investigate these genes better; we observed that the treatment with E3330 and Resveratrol down regulates many mitochondrial genes involved in the pathogenesis of diseases such as Parkinson and Alzheimer.
publishDate 2017
dc.date.issued.fl_str_mv 2017
dc.date.accessioned.fl_str_mv 2018-04-03T13:55:50Z
2021-10-06T11:14:59Z
dc.date.available.fl_str_mv 2018-04-03T13:55:50Z
2021-10-06T11:14:59Z
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dc.identifier.citation.fl_str_mv OLIVEIRA, Thais Teixeira. Alteração da expressão de genes relacionados a doenças neurodegenerativas em modelos inflamatórios tratados com inibidores de APE1. 2017. 79 f. Trabalho de Conclusão de Curso (Graduação em Biomedicina) - Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal-RN, 2017.
dc.identifier.uri.fl_str_mv https://repositorio.ufrn.br/handle/123456789/43174
identifier_str_mv 2012912160
OLIVEIRA, Thais Teixeira. Alteração da expressão de genes relacionados a doenças neurodegenerativas em modelos inflamatórios tratados com inibidores de APE1. 2017. 79 f. Trabalho de Conclusão de Curso (Graduação em Biomedicina) - Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal-RN, 2017.
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