Modelagem lógica de senescência celular humana
Autor(a) principal: | |
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Data de Publicação: | 2012 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional Manancial UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/9235 |
Resumo: | After the progressive telomere shortening in successive cell divisions, normal somatic cells undergo a growth arrest called cellular senescence that occurs due to incomplete DNA replication. Senescence can also be activated by various types of stressful stimuli, including aberrant oncogenic signaling, oxidative stress and DNA damage. Senescent cells have limited proliferative capacity and seems to play an important role in tumorigenesis. They are also involved in the inflammation associated with aging and cancer progression. The process of senescence vary significantly between cells, but the different paths for the aging, however, converge to p53 and pRB. The network simulation is based on the model proposed by Porath using a Boolean model to represent the state of activation of genes involved, including the p16-pRb and p53-p21 pathways. The simulation includes 23 nodes representing the genes of the regulatory network where one of them represents the activation of the senescent state as a result of network processing. Experiments with human fibroblasts indicate that inactivation of both genes, p53 and pRB is necessary to block senescence. The simulations confirms that these pathways are able to trigger senescence independently. The simulation shows that pRb is essential to maintain the senescent state even when p16 and p53 are switched off, but the simultaneous inactivation of both p53 and pRB blocks senescence. In addition, the simulation shows that inactivation of the p16-pRb pathway is not essential to preserve the senescent state, however when p53-p21 pathway is inactivated, the senescent state is preserved. |
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2017-05-042017-05-042012-12-12FERREIRA, Cecilia Perobelli. Logic modeling of human cell senescence. 2012. 62 f. Dissertação (Mestrado em Física) - Universidade Federal de Santa Maria, Santa Maria, 2012.http://repositorio.ufsm.br/handle/1/9235After the progressive telomere shortening in successive cell divisions, normal somatic cells undergo a growth arrest called cellular senescence that occurs due to incomplete DNA replication. Senescence can also be activated by various types of stressful stimuli, including aberrant oncogenic signaling, oxidative stress and DNA damage. Senescent cells have limited proliferative capacity and seems to play an important role in tumorigenesis. They are also involved in the inflammation associated with aging and cancer progression. The process of senescence vary significantly between cells, but the different paths for the aging, however, converge to p53 and pRB. The network simulation is based on the model proposed by Porath using a Boolean model to represent the state of activation of genes involved, including the p16-pRb and p53-p21 pathways. The simulation includes 23 nodes representing the genes of the regulatory network where one of them represents the activation of the senescent state as a result of network processing. Experiments with human fibroblasts indicate that inactivation of both genes, p53 and pRB is necessary to block senescence. The simulations confirms that these pathways are able to trigger senescence independently. The simulation shows that pRb is essential to maintain the senescent state even when p16 and p53 are switched off, but the simultaneous inactivation of both p53 and pRB blocks senescence. In addition, the simulation shows that inactivation of the p16-pRb pathway is not essential to preserve the senescent state, however when p53-p21 pathway is inactivated, the senescent state is preserved.Após o progressivo encurtamento dos telômeros em sucessivas divisões celulares, as células somáticas normais se submetidas a uma parada do crescimento chamado senescência celular que ocorre devido à replicação incompleta do DNA. A senescência também pode ser ativada por diversos tipos de estímulos estressantes, incluindo sinalização oncogênica aberrante, estresse oxidativo e danos ao DNA. Células senescentes têm capacidade proliferativa limitada e parecem desempenhar um papel importante na tumorigênese. Elas também estão envolvidas na inflamação associada com o envelhecimento e progressão do câncer. As vias de senescência variam significativamente entre as células, mas os caminhos diversos para a senescência, no entanto, convergem para p53 e pRb. A simulação é baseada no modelo proposto por Porath usando um modelo booleano para representar o estado de ativação dos genes envolvidos, incluindo as vias p16-pRb e a p53-p21. A simulação inclui 23 nós representando os genes da rede regulatória onde um deles representa o estado celular senescente que pode assumir estados Verdadeiro ou Falso como resultado do processamento de rede Experiências com fibroblastos humanos indicam que a inativação de ambos os genes, p53 e pRb, é necessária para bloquear a senescência. As simulações confirmam que essas vias são capazes de acionar a senescência independentemente. A simulação mostra que pRb é essencial para a manutenção do estado senescente mesmo se p16 e p53 forem desligados, no entanto a inativação simultânea de ambos p53 e pRb bloqueia senescência. Além disso, a simulação mostra que a inativação da via p16-pRb não é essencial para preservar o estado senescente, no entanto, quando a via p53-p21 é inativada, o estado senescente é preservado.Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em FísicaUFSMBRFísicaSenescência celularTumorigêneseCâncerModelo BooleanoCellular senescenceTumorigenesisCancerBoolean modelCNPQ::CIENCIAS EXATAS E DA TERRA::FISICAModelagem lógica de senescência celular humanaLogic modeling of human cell senescenceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisMombach, Jose Carlos Merinohttp://lattes.cnpq.br/7661373078999069Zimmer, Fábio Mallmannhttp://lattes.cnpq.br/6328420212181284Vêncio, Ricardo Zorzetto Nicoliellohttp://lattes.cnpq.br/3278315914566734http://lattes.cnpq.br/0212806448554128Ferreira, Cecilia Perobelli1005000000064005003003003003f068138-f520-468d-b0ab-7f831fb4573323fd4c63-409e-4b5a-a147-a9f7014ed210d7b3340c-46e5-4175-a809-8538c22a1b92d5dd3b8f-1fe6-464a-8d1a-9eb0bf929edainfo:eu-repo/semantics/openAccessreponame:Repositório Institucional Manancial UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALFERREIRA, CECILIA PEROBELLI.pdfapplication/pdf2788602http://repositorio.ufsm.br/bitstream/1/9235/1/FERREIRA%2c%20CECILIA%20PEROBELLI.pdfd744cd451ee460562b67092ccc7e8ab8MD51TEXTFERREIRA, CECILIA PEROBELLI.pdf.txtFERREIRA, CECILIA PEROBELLI.pdf.txtExtracted texttext/plain107660http://repositorio.ufsm.br/bitstream/1/9235/2/FERREIRA%2c%20CECILIA%20PEROBELLI.pdf.txt08e996051901699b4dcc3e068011a648MD52THUMBNAILFERREIRA, CECILIA PEROBELLI.pdf.jpgFERREIRA, CECILIA PEROBELLI.pdf.jpgIM Thumbnailimage/jpeg4602http://repositorio.ufsm.br/bitstream/1/9235/3/FERREIRA%2c%20CECILIA%20PEROBELLI.pdf.jpgceabdfc6601a2be574aeff308d40c0b9MD531/92352022-06-23 12:48:14.053oai:repositorio.ufsm.br:1/9235Repositório Institucionalhttp://repositorio.ufsm.br/PUBhttp://repositorio.ufsm.br/oai/requestouvidoria@ufsm.bropendoar:39132022-06-23T15:48:14Repositório Institucional Manancial UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Modelagem lógica de senescência celular humana |
dc.title.alternative.eng.fl_str_mv |
Logic modeling of human cell senescence |
title |
Modelagem lógica de senescência celular humana |
spellingShingle |
Modelagem lógica de senescência celular humana Ferreira, Cecilia Perobelli Senescência celular Tumorigênese Câncer Modelo Booleano Cellular senescence Tumorigenesis Cancer Boolean model CNPQ::CIENCIAS EXATAS E DA TERRA::FISICA |
title_short |
Modelagem lógica de senescência celular humana |
title_full |
Modelagem lógica de senescência celular humana |
title_fullStr |
Modelagem lógica de senescência celular humana |
title_full_unstemmed |
Modelagem lógica de senescência celular humana |
title_sort |
Modelagem lógica de senescência celular humana |
author |
Ferreira, Cecilia Perobelli |
author_facet |
Ferreira, Cecilia Perobelli |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Mombach, Jose Carlos Merino |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/7661373078999069 |
dc.contributor.referee1.fl_str_mv |
Zimmer, Fábio Mallmann |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/6328420212181284 |
dc.contributor.referee2.fl_str_mv |
Vêncio, Ricardo Zorzetto Nicoliello |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/3278315914566734 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/0212806448554128 |
dc.contributor.author.fl_str_mv |
Ferreira, Cecilia Perobelli |
contributor_str_mv |
Mombach, Jose Carlos Merino Zimmer, Fábio Mallmann Vêncio, Ricardo Zorzetto Nicoliello |
dc.subject.por.fl_str_mv |
Senescência celular Tumorigênese Câncer Modelo Booleano |
topic |
Senescência celular Tumorigênese Câncer Modelo Booleano Cellular senescence Tumorigenesis Cancer Boolean model CNPQ::CIENCIAS EXATAS E DA TERRA::FISICA |
dc.subject.eng.fl_str_mv |
Cellular senescence Tumorigenesis Cancer Boolean model |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS EXATAS E DA TERRA::FISICA |
description |
After the progressive telomere shortening in successive cell divisions, normal somatic cells undergo a growth arrest called cellular senescence that occurs due to incomplete DNA replication. Senescence can also be activated by various types of stressful stimuli, including aberrant oncogenic signaling, oxidative stress and DNA damage. Senescent cells have limited proliferative capacity and seems to play an important role in tumorigenesis. They are also involved in the inflammation associated with aging and cancer progression. The process of senescence vary significantly between cells, but the different paths for the aging, however, converge to p53 and pRB. The network simulation is based on the model proposed by Porath using a Boolean model to represent the state of activation of genes involved, including the p16-pRb and p53-p21 pathways. The simulation includes 23 nodes representing the genes of the regulatory network where one of them represents the activation of the senescent state as a result of network processing. Experiments with human fibroblasts indicate that inactivation of both genes, p53 and pRB is necessary to block senescence. The simulations confirms that these pathways are able to trigger senescence independently. The simulation shows that pRb is essential to maintain the senescent state even when p16 and p53 are switched off, but the simultaneous inactivation of both p53 and pRB blocks senescence. In addition, the simulation shows that inactivation of the p16-pRb pathway is not essential to preserve the senescent state, however when p53-p21 pathway is inactivated, the senescent state is preserved. |
publishDate |
2012 |
dc.date.issued.fl_str_mv |
2012-12-12 |
dc.date.accessioned.fl_str_mv |
2017-05-04 |
dc.date.available.fl_str_mv |
2017-05-04 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
FERREIRA, Cecilia Perobelli. Logic modeling of human cell senescence. 2012. 62 f. Dissertação (Mestrado em Física) - Universidade Federal de Santa Maria, Santa Maria, 2012. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/9235 |
identifier_str_mv |
FERREIRA, Cecilia Perobelli. Logic modeling of human cell senescence. 2012. 62 f. Dissertação (Mestrado em Física) - Universidade Federal de Santa Maria, Santa Maria, 2012. |
url |
http://repositorio.ufsm.br/handle/1/9235 |
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openAccess |
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Universidade Federal de Santa Maria |
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UFSM |
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Física |
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Universidade Federal de Santa Maria |
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