Ação da rutina em um modelo de exposição aos metais cobre e zinco em Caenorhabditis elegans com superprodução de huntingtina
Ano de defesa: | 2023 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , , , |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
Centro de Ciências Naturais e Exatas |
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
|
Departamento: |
Bioquímica
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/30740 |
Resumo: | Huntington's disease (HD) is a progressive, hereditary neurodegenerative disease caused due to a mutation in the huntingtin gene that contains an abnormal expansion of cytosine-adenineguanine (CAG) repeats, leading to a polyglutamine (polyQ) chain of variable length. The mutation confers toxic functions on the mutant huntingtin protein, causing neurodegeneration. HD pathology results in loss of neuronal cells, motor changes, dementia and is currently a disease with no cure. It is known that metal accumulation is found in the pathologically affected regions of many neurodegenerative diseases. The essential metals Copper and Zinc are necessary in small concentrations for metabolic functions, but can, however, produce toxic effects in high concentrations. Furthermore, there is great concern regarding environmental pollution by metals, as urban environments are places subject to significant levels of contamination and, consequently, are the areas with the greatest exposure of metals to the population, whether through inhalation of dust or ingestion of contaminated soil through food. Rutin is a flavonoid found in several plants, such as buckwheat, some teas and fruits, making it easily accessible and low cost to the entire population. Therefore, this work investigated the effect of rutin on neurotoxic effects caused by Copper and Zinc in a HD model in Caenorhabditis elegans. The evaluation of the mixture of metals in chronic form and concentrations permitted by Brazilian legislation regarding residential soils was investigated for the first time. In general, exposure to metals and their mixture led to locomotor and body changes, in addition to a delay in the development of the worms, and affected behaviors related to ASH neurons and touch receptor neurons. Furthermore, it caused an increase in muscle and neuronal protein aggregates, leading to neurodegeneration. The neuroprotective effect of rutin was verified, the flavonoid was able to reduce protein aggregates and neurodegeneration. It has been proposed that rutin acts through mechanisms involving antioxidant properties, through increased expression of antioxidant enzymes and chaperones, in addition to acting against metals. Taken together, our data provide new insights into the guiding values of soil quality, analyzed chronically and in mixed metals, as well as new strategies for future treatments of neurodegenerative diseases caused by the aggregation of metal-related proteins. |
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2023-11-30T19:06:34Z2023-11-30T19:06:34Z2023-11-17http://repositorio.ufsm.br/handle/1/30740Huntington's disease (HD) is a progressive, hereditary neurodegenerative disease caused due to a mutation in the huntingtin gene that contains an abnormal expansion of cytosine-adenineguanine (CAG) repeats, leading to a polyglutamine (polyQ) chain of variable length. The mutation confers toxic functions on the mutant huntingtin protein, causing neurodegeneration. HD pathology results in loss of neuronal cells, motor changes, dementia and is currently a disease with no cure. It is known that metal accumulation is found in the pathologically affected regions of many neurodegenerative diseases. The essential metals Copper and Zinc are necessary in small concentrations for metabolic functions, but can, however, produce toxic effects in high concentrations. Furthermore, there is great concern regarding environmental pollution by metals, as urban environments are places subject to significant levels of contamination and, consequently, are the areas with the greatest exposure of metals to the population, whether through inhalation of dust or ingestion of contaminated soil through food. Rutin is a flavonoid found in several plants, such as buckwheat, some teas and fruits, making it easily accessible and low cost to the entire population. Therefore, this work investigated the effect of rutin on neurotoxic effects caused by Copper and Zinc in a HD model in Caenorhabditis elegans. The evaluation of the mixture of metals in chronic form and concentrations permitted by Brazilian legislation regarding residential soils was investigated for the first time. In general, exposure to metals and their mixture led to locomotor and body changes, in addition to a delay in the development of the worms, and affected behaviors related to ASH neurons and touch receptor neurons. Furthermore, it caused an increase in muscle and neuronal protein aggregates, leading to neurodegeneration. The neuroprotective effect of rutin was verified, the flavonoid was able to reduce protein aggregates and neurodegeneration. It has been proposed that rutin acts through mechanisms involving antioxidant properties, through increased expression of antioxidant enzymes and chaperones, in addition to acting against metals. Taken together, our data provide new insights into the guiding values of soil quality, analyzed chronically and in mixed metals, as well as new strategies for future treatments of neurodegenerative diseases caused by the aggregation of metal-related proteins.A doença de Huntington (DH) é uma doença neurodegenerativa progressiva e hereditária causada devido a uma mutação no gene da huntingtina que contém uma expansão anormal das repetições da citosina-adenina-guanina (CAG), levando a uma cadeia de poliglutamina (poliQ) de comprimento variável. A mutação confere funções tóxicas à proteína huntingtina mutante, causando neurodegeneração. A patologia de DH resulta em perda de células neuronais, alterações motoras, demência e atualmente é uma doença sem cura. É sabido que o acúmulo de metais é encontrado nas regiões patologicamente afetadas de muitas doenças neurodegenerativas. Os metais essenciais Cobre e Zinco são necessários em pequenas concentrações para funções metabólicas, podendo, entretanto, produzir efeitos tóxicos em concentrações elevadas. Além disso existe uma grande preocupação quanto a poluição ambiental por metais, sendo que os ambientes urbanos são locais sujeitos a significativos níveis de contaminação e, consequentemente, são as áreas de maior exposição de metais a população, seja pela inalação de poeira ou pela ingestão de solo contaminado através de alimentos. A rutina é um flavonóide encontrado em várias plantas, como o trigo sarraceno, alguns chás e frutas, sendo assim, de fácil acesso e baixo custo a toda população. Portanto, esse trabalho investigou o efeito da rutina sobre efeitos neurotóxicos causados por Cobre e Zinco em um modelo de DH em Caenorhabditis elegans. A avaliação da mistura de metais de forma crônica e concentrações permitidas pela legislação brasileira referentes a solos residencias foi investigada pela primeira vez. No geral, a exposição aos metais e sua mistura levou a alterações locomotoras, corporais, além de um atraso no desenvolvimento dos vermes, afetou comportamentos relacionados aos neurônios ASH e neurônios receptores de toque. Ademais, causou um aumento nos agregados proteicos musculares e neuronais, levando a neurodegeneração. Verificou-se o efeito neuroprotetor da rutina, o flavoinoide foi capaz de diminuir os agregados proteicos e a neurodegeneração. Propôs-se que a rutina atue através de mecanismos que envolvam propriedades antioxidantes, através do aumento da expressão de enzimas antioxidantes e chaperonas, além de atuar contra os metais. Em conjunto, nossos dados fornecem novas indicações sobre os valores orientadores da qualidade do solo, analisados de forma crônica e em mistura de metais, além de novas estratégias para futuros tratamentos de doenças neurodegenerativas causadas pela agregação de proteínas relacionadas a metais.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade Federal de Santa MariaCentro de Ciências Naturais e ExatasPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBrasilBioquímicaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessNeuroproteçãoNeurodegeneraçãoFlavonoidesC. elegansMistura de metaisSolo brasileiroNeuroprotectionNeurodegenerationFlavonoidsMixture of metalsBrazilian soilCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAAção da rutina em um modelo de exposição aos metais cobre e zinco em Caenorhabditis elegans com superprodução de huntingtinaAction of rutin in a model of exposure to copper and zinc metals in Caenorhabditis elegans with huntingtin overproductioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisSoares, Félix Alexandre Antuneshttp://lattes.cnpq.br/8752453650114092Charão, Mariele FeifferRosemberg, Denis BroockAugusti, Paula RossiniFarina, Marcelohttp://lattes.cnpq.br/9646328956877026Cordeiro, Larissa Marafiga2008000000026006006006006006006003aef53b7-b173-4c56-a944-bed2de5e5ddaf5950a75-7ceb-45b8-a15e-d0bf5f1b4236ed586806-0479-44eb-914e-4c644d9cb6428ade1f91-8aa4-433a-8948-aa845c5ce69d56fad85d-b2b9-4349-8d55-290cd51d87bb822f236d-eced-480d-af90-91ec86ad99c1reponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Ação da rutina em um modelo de exposição aos metais cobre e zinco em Caenorhabditis elegans com superprodução de huntingtina |
dc.title.alternative.eng.fl_str_mv |
Action of rutin in a model of exposure to copper and zinc metals in Caenorhabditis elegans with huntingtin overproduction |
title |
Ação da rutina em um modelo de exposição aos metais cobre e zinco em Caenorhabditis elegans com superprodução de huntingtina |
spellingShingle |
Ação da rutina em um modelo de exposição aos metais cobre e zinco em Caenorhabditis elegans com superprodução de huntingtina Cordeiro, Larissa Marafiga Neuroproteção Neurodegeneração Flavonoides C. elegans Mistura de metais Solo brasileiro Neuroprotection Neurodegeneration Flavonoids Mixture of metals Brazilian soil CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Ação da rutina em um modelo de exposição aos metais cobre e zinco em Caenorhabditis elegans com superprodução de huntingtina |
title_full |
Ação da rutina em um modelo de exposição aos metais cobre e zinco em Caenorhabditis elegans com superprodução de huntingtina |
title_fullStr |
Ação da rutina em um modelo de exposição aos metais cobre e zinco em Caenorhabditis elegans com superprodução de huntingtina |
title_full_unstemmed |
Ação da rutina em um modelo de exposição aos metais cobre e zinco em Caenorhabditis elegans com superprodução de huntingtina |
title_sort |
Ação da rutina em um modelo de exposição aos metais cobre e zinco em Caenorhabditis elegans com superprodução de huntingtina |
author |
Cordeiro, Larissa Marafiga |
author_facet |
Cordeiro, Larissa Marafiga |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Soares, Félix Alexandre Antunes |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/8752453650114092 |
dc.contributor.referee1.fl_str_mv |
Charão, Mariele Feiffer |
dc.contributor.referee2.fl_str_mv |
Rosemberg, Denis Broock |
dc.contributor.referee3.fl_str_mv |
Augusti, Paula Rossini |
dc.contributor.referee4.fl_str_mv |
Farina, Marcelo |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/9646328956877026 |
dc.contributor.author.fl_str_mv |
Cordeiro, Larissa Marafiga |
contributor_str_mv |
Soares, Félix Alexandre Antunes Charão, Mariele Feiffer Rosemberg, Denis Broock Augusti, Paula Rossini Farina, Marcelo |
dc.subject.por.fl_str_mv |
Neuroproteção Neurodegeneração Flavonoides C. elegans Mistura de metais Solo brasileiro |
topic |
Neuroproteção Neurodegeneração Flavonoides C. elegans Mistura de metais Solo brasileiro Neuroprotection Neurodegeneration Flavonoids Mixture of metals Brazilian soil CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Neuroprotection Neurodegeneration Flavonoids Mixture of metals Brazilian soil |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Huntington's disease (HD) is a progressive, hereditary neurodegenerative disease caused due to a mutation in the huntingtin gene that contains an abnormal expansion of cytosine-adenineguanine (CAG) repeats, leading to a polyglutamine (polyQ) chain of variable length. The mutation confers toxic functions on the mutant huntingtin protein, causing neurodegeneration. HD pathology results in loss of neuronal cells, motor changes, dementia and is currently a disease with no cure. It is known that metal accumulation is found in the pathologically affected regions of many neurodegenerative diseases. The essential metals Copper and Zinc are necessary in small concentrations for metabolic functions, but can, however, produce toxic effects in high concentrations. Furthermore, there is great concern regarding environmental pollution by metals, as urban environments are places subject to significant levels of contamination and, consequently, are the areas with the greatest exposure of metals to the population, whether through inhalation of dust or ingestion of contaminated soil through food. Rutin is a flavonoid found in several plants, such as buckwheat, some teas and fruits, making it easily accessible and low cost to the entire population. Therefore, this work investigated the effect of rutin on neurotoxic effects caused by Copper and Zinc in a HD model in Caenorhabditis elegans. The evaluation of the mixture of metals in chronic form and concentrations permitted by Brazilian legislation regarding residential soils was investigated for the first time. In general, exposure to metals and their mixture led to locomotor and body changes, in addition to a delay in the development of the worms, and affected behaviors related to ASH neurons and touch receptor neurons. Furthermore, it caused an increase in muscle and neuronal protein aggregates, leading to neurodegeneration. The neuroprotective effect of rutin was verified, the flavonoid was able to reduce protein aggregates and neurodegeneration. It has been proposed that rutin acts through mechanisms involving antioxidant properties, through increased expression of antioxidant enzymes and chaperones, in addition to acting against metals. Taken together, our data provide new insights into the guiding values of soil quality, analyzed chronically and in mixed metals, as well as new strategies for future treatments of neurodegenerative diseases caused by the aggregation of metal-related proteins. |
publishDate |
2023 |
dc.date.accessioned.fl_str_mv |
2023-11-30T19:06:34Z |
dc.date.available.fl_str_mv |
2023-11-30T19:06:34Z |
dc.date.issued.fl_str_mv |
2023-11-17 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
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http://repositorio.ufsm.br/handle/1/30740 |
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http://repositorio.ufsm.br/handle/1/30740 |
dc.language.iso.fl_str_mv |
por |
language |
por |
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200800000002 |
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600 600 600 600 600 600 600 |
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Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Bioquímica |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
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