O papel do polimorfismo Ala16Val da Mn-SOD no acidente vascular encefálico crônico: um estudo clínico
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/19216 |
Resumo: | Considered one of the most common neurological diseases, stroke has a high morbidity and mortality, and corresponds to 85% of disease cases. Several factors are involved in disease etiology, such as changes in vascular permeability, oxidative stress, inflammation, apoptosis and DNA damage. Among the main consequences are cognitive and motor deficits, depending on the level and time of injury. The single nucleotide polymorphism Ala16Val (SNP) is a genetic mutation of the antioxidant enzyme superoxide dismutase and is associated with the risk factors of metabolic and vascular diseases, such as stroke. Brain derived neurotrophic (BDNF) is a neurotrofin that, among various functions, is associated with tissue regeneration after cerebrovascular lesions. Acetylcholine (ACh) is a neurotransmitter related to mnemonic processes, learning and motor functions. Thus, this study was to investigate the relationship between the polymorphism Ala16Val with oxidative, inflammatory, apoptotics and DNA damage markers, as well, with levels of BDNF, ACh, memory and functional capacity of chronic stroke patients. Fourthy-eight ischemic stroke patients with and fifthy healthy controls were subjected to questionnaires, laboratory tests and clinical trials. The results showed a higher proportion of the VV genotype in stroke patients compared to healthy individuals. VV genotype patients also showed higher levels of 2 -7 ′ ′ diclorofluorescein diacetate (DCFH-DA), nitrite/nitrate (NOX), tumor necrosis factor-α (TNF-α), acetylcholinesterase (AChE), caspase 8 (CASP 8), caspase 3 (CASP 3) and PicoGreen (PG), as well as decreased levels of BDNF and ACh. Similarly, in cognitive tests (working memory and total memory) and tests (Berg Balance scale and the senior fitness test-STF), VV genotype patients had worse results when compared with the other genotypes (stroke and control groups). In this way, the results suggest a relationship of polymorphism Ala16Val with oxidative/nitrosatve and inflammatory routes, culminated in activation of the apoptotic cascade and DNA damage, especially for VV genotype patients. Moreover, VV patients showed worst results in cognitive and motor tests, as well as low BDNF and ACh levels. Thus, is plausible to suggest that VV patients with present a worse performance in relation to cognitive and motor function, as well as increase in oxidative and inflammatory parameters. Our findings also related clinical changes reduced levels of BDNF and ACh, suggesting that knowledge of Mn-SOD polymorphism is important to evaluate the molecular mechanisms associated with neurovascular lesion and offer a individualized treatment for these patients. |
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O papel do polimorfismo Ala16Val da Mn-SOD no acidente vascular encefálico crônico: um estudo clínicoThe role of the Ala16Val Mn-SOD polymorphism in chronic stroke: a clinical studyAcidente vascular encefálicoEstresse oxidativoInflamaçãoApoptoseDano ao DNAMemóriaFuncionalidadeStrokeOxidative stressInflammationApoptosisDNA damageMemoryFuncionalityCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAConsidered one of the most common neurological diseases, stroke has a high morbidity and mortality, and corresponds to 85% of disease cases. Several factors are involved in disease etiology, such as changes in vascular permeability, oxidative stress, inflammation, apoptosis and DNA damage. Among the main consequences are cognitive and motor deficits, depending on the level and time of injury. The single nucleotide polymorphism Ala16Val (SNP) is a genetic mutation of the antioxidant enzyme superoxide dismutase and is associated with the risk factors of metabolic and vascular diseases, such as stroke. Brain derived neurotrophic (BDNF) is a neurotrofin that, among various functions, is associated with tissue regeneration after cerebrovascular lesions. Acetylcholine (ACh) is a neurotransmitter related to mnemonic processes, learning and motor functions. Thus, this study was to investigate the relationship between the polymorphism Ala16Val with oxidative, inflammatory, apoptotics and DNA damage markers, as well, with levels of BDNF, ACh, memory and functional capacity of chronic stroke patients. Fourthy-eight ischemic stroke patients with and fifthy healthy controls were subjected to questionnaires, laboratory tests and clinical trials. The results showed a higher proportion of the VV genotype in stroke patients compared to healthy individuals. VV genotype patients also showed higher levels of 2 -7 ′ ′ diclorofluorescein diacetate (DCFH-DA), nitrite/nitrate (NOX), tumor necrosis factor-α (TNF-α), acetylcholinesterase (AChE), caspase 8 (CASP 8), caspase 3 (CASP 3) and PicoGreen (PG), as well as decreased levels of BDNF and ACh. Similarly, in cognitive tests (working memory and total memory) and tests (Berg Balance scale and the senior fitness test-STF), VV genotype patients had worse results when compared with the other genotypes (stroke and control groups). In this way, the results suggest a relationship of polymorphism Ala16Val with oxidative/nitrosatve and inflammatory routes, culminated in activation of the apoptotic cascade and DNA damage, especially for VV genotype patients. Moreover, VV patients showed worst results in cognitive and motor tests, as well as low BDNF and ACh levels. Thus, is plausible to suggest that VV patients with present a worse performance in relation to cognitive and motor function, as well as increase in oxidative and inflammatory parameters. Our findings also related clinical changes reduced levels of BDNF and ACh, suggesting that knowledge of Mn-SOD polymorphism is important to evaluate the molecular mechanisms associated with neurovascular lesion and offer a individualized treatment for these patients.Considerada uma das doenças neurológicas mais frequentes, o acidente vascular encefálico (AVE) apresenta uma alta taxa de morbidade e mortalidade, sendo que o AVE isquêmico corresponde a 85% dos casos. Diversos fatores estão envolvidos na etiologia da doença, como alterações na permeabilidade vascular, estresse oxidativo, inflamação, apoptose e dano ao DNA. Entre outras consequências estão os déficits cognitivos e motores, dependendo da magnitude e tempo da lesão. O polimorfismo de nucleotídeo único MnSOD Ala16Val (SNP) é uma mutação genética da enzima antioxidante superóxido dismutase e está associado a fatores de risco de doenças metabólicas e vasculares, como o AVE. O fator neurotrófico derivado do encéfalo (BDNF) é uma neurotrofina que, entre várias funções, está associada a regeneração tecidual após lesões vasculares cerebrais. A acetilcolina (ACh) é um neurotransmissor excitatório relacionado com processos mnemônicos, aprendizado e funções motoras. Desta forma, foi objetivo deste estudo investigar a relação entre o polimorfismo da Ala16Val MnSOD com os marcadores oxidativos, inflamatórios, apoptóticos e de dano ao DNA, bem como, com os níveis de BDNF, ACh e atividade da AChE, memória e a capacidade funcional de pacientes após-AVE crônico isquêmico (AVEi) crônico. Quarenta e oito pacientes com AVE e 50 controles saudáveis foram submetidos a questionários, exames laboratoriais e testes clínicos. Os resultados mostraram uma maior proporção do genótipo VV nos pacientes após-AVE em comparação com indivíduos saudáveis. Os pacientes com genótipo VV também apresentaram níveis mais elevados de 2′-7′ diacetato de diclorofluoresceina (DCFH-DA), nitrito/nitrato (NOX), fator de necrose tumoral-α (TNF-α), acetilcolinesterase (AChE), caspase 8 (CASP 8), caspase 3 (CASP 3) e PicoGreen (PG), bem como, níveis diminuídos de BDNF e ACh. Similarmente, nos testes cognitivos (memória de trabalho e memória total) e nos testes motores (Escala de Equilíbrio de Berg e o teste fitness sênior - STF), os pacientes com genótipo VV tiveram piores resultados quando comparados com os outros genótipos (grupo AVE e controles). Desta forma, os resultados sugerem uma relação do polimorfismo da MnSOD Ala16Val com as rotas oxidativa/nitrosativa e inflamatória, culminado na ativação da cascata apoptótica e dano a DNA, especialmente para aqueles pacientes com genótipo VV. Além disso, os pacientes (VV) mostraram os piores resultados nos testes cognitivos e motores, assim como, níveis reduzidos de BDNF, ACh e atividade da AChE. Assim, é plausível propor que pacientes com AVEi com genótipo VV apresentam um pior desempenho em relaçõ à função cognitiva e motora, assim como, aumento nos parâmetros oxidativos e inflamatórios. Nossos achados também relacionaram as alterações clínicas aos níveis reduzidos de BDNF e ACh, sugerindo que o conhecimento da existência do polimorfismo é importante para avaliar os mecanismos moleculares associados à lesão neurovascular e oferecer um tratamento individualizado para esses pacientes.Universidade Federal de Santa MariaBrasilBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaCentro de Ciências Naturais e ExatasFighera, Michele Rechiahttp://lattes.cnpq.br/8583392747509231Nascimento, Patrícia Severo dohttp://lattes.cnpq.br/6497514350134284Chitolina, Maria Rosahttp://lattes.cnpq.br/4401319386725357Werner, Maria Fernanda de Paulahttp://lattes.cnpq.br/9053828782958389Barcelos, Rômulo Pillonhttp://lattes.cnpq.br/8887253904142575Pascotini, Eduardo Tanuri2019-12-23T13:49:18Z2019-12-23T13:49:18Z2019-08-17info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/19216porAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2019-12-24T06:02:26Zoai:repositorio.ufsm.br:1/19216Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2019-12-24T06:02:26Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
O papel do polimorfismo Ala16Val da Mn-SOD no acidente vascular encefálico crônico: um estudo clínico The role of the Ala16Val Mn-SOD polymorphism in chronic stroke: a clinical study |
title |
O papel do polimorfismo Ala16Val da Mn-SOD no acidente vascular encefálico crônico: um estudo clínico |
spellingShingle |
O papel do polimorfismo Ala16Val da Mn-SOD no acidente vascular encefálico crônico: um estudo clínico Pascotini, Eduardo Tanuri Acidente vascular encefálico Estresse oxidativo Inflamação Apoptose Dano ao DNA Memória Funcionalidade Stroke Oxidative stress Inflammation Apoptosis DNA damage Memory Funcionality CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
O papel do polimorfismo Ala16Val da Mn-SOD no acidente vascular encefálico crônico: um estudo clínico |
title_full |
O papel do polimorfismo Ala16Val da Mn-SOD no acidente vascular encefálico crônico: um estudo clínico |
title_fullStr |
O papel do polimorfismo Ala16Val da Mn-SOD no acidente vascular encefálico crônico: um estudo clínico |
title_full_unstemmed |
O papel do polimorfismo Ala16Val da Mn-SOD no acidente vascular encefálico crônico: um estudo clínico |
title_sort |
O papel do polimorfismo Ala16Val da Mn-SOD no acidente vascular encefálico crônico: um estudo clínico |
author |
Pascotini, Eduardo Tanuri |
author_facet |
Pascotini, Eduardo Tanuri |
author_role |
author |
dc.contributor.none.fl_str_mv |
Fighera, Michele Rechia http://lattes.cnpq.br/8583392747509231 Nascimento, Patrícia Severo do http://lattes.cnpq.br/6497514350134284 Chitolina, Maria Rosa http://lattes.cnpq.br/4401319386725357 Werner, Maria Fernanda de Paula http://lattes.cnpq.br/9053828782958389 Barcelos, Rômulo Pillon http://lattes.cnpq.br/8887253904142575 |
dc.contributor.author.fl_str_mv |
Pascotini, Eduardo Tanuri |
dc.subject.por.fl_str_mv |
Acidente vascular encefálico Estresse oxidativo Inflamação Apoptose Dano ao DNA Memória Funcionalidade Stroke Oxidative stress Inflammation Apoptosis DNA damage Memory Funcionality CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
topic |
Acidente vascular encefálico Estresse oxidativo Inflamação Apoptose Dano ao DNA Memória Funcionalidade Stroke Oxidative stress Inflammation Apoptosis DNA damage Memory Funcionality CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Considered one of the most common neurological diseases, stroke has a high morbidity and mortality, and corresponds to 85% of disease cases. Several factors are involved in disease etiology, such as changes in vascular permeability, oxidative stress, inflammation, apoptosis and DNA damage. Among the main consequences are cognitive and motor deficits, depending on the level and time of injury. The single nucleotide polymorphism Ala16Val (SNP) is a genetic mutation of the antioxidant enzyme superoxide dismutase and is associated with the risk factors of metabolic and vascular diseases, such as stroke. Brain derived neurotrophic (BDNF) is a neurotrofin that, among various functions, is associated with tissue regeneration after cerebrovascular lesions. Acetylcholine (ACh) is a neurotransmitter related to mnemonic processes, learning and motor functions. Thus, this study was to investigate the relationship between the polymorphism Ala16Val with oxidative, inflammatory, apoptotics and DNA damage markers, as well, with levels of BDNF, ACh, memory and functional capacity of chronic stroke patients. Fourthy-eight ischemic stroke patients with and fifthy healthy controls were subjected to questionnaires, laboratory tests and clinical trials. The results showed a higher proportion of the VV genotype in stroke patients compared to healthy individuals. VV genotype patients also showed higher levels of 2 -7 ′ ′ diclorofluorescein diacetate (DCFH-DA), nitrite/nitrate (NOX), tumor necrosis factor-α (TNF-α), acetylcholinesterase (AChE), caspase 8 (CASP 8), caspase 3 (CASP 3) and PicoGreen (PG), as well as decreased levels of BDNF and ACh. Similarly, in cognitive tests (working memory and total memory) and tests (Berg Balance scale and the senior fitness test-STF), VV genotype patients had worse results when compared with the other genotypes (stroke and control groups). In this way, the results suggest a relationship of polymorphism Ala16Val with oxidative/nitrosatve and inflammatory routes, culminated in activation of the apoptotic cascade and DNA damage, especially for VV genotype patients. Moreover, VV patients showed worst results in cognitive and motor tests, as well as low BDNF and ACh levels. Thus, is plausible to suggest that VV patients with present a worse performance in relation to cognitive and motor function, as well as increase in oxidative and inflammatory parameters. Our findings also related clinical changes reduced levels of BDNF and ACh, suggesting that knowledge of Mn-SOD polymorphism is important to evaluate the molecular mechanisms associated with neurovascular lesion and offer a individualized treatment for these patients. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-12-23T13:49:18Z 2019-12-23T13:49:18Z 2019-08-17 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/19216 |
url |
http://repositorio.ufsm.br/handle/1/19216 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica Centro de Ciências Naturais e Exatas |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica Centro de Ciências Naturais e Exatas |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
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1805922151380811776 |