Insulin glycation by methylglyoxal results in native-like aggregation and inhibition of fibril formation

Detalhes bibliográficos
Autor(a) principal: Oliveira, Luis MA
Data de Publicação: 2011
Outros Autores: Lages, Ana, Gomes, Ricardo A, Neves, Henrique, Família, Carlos, Coelho, Ana V, Quintas, Alexandre
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.26/4824
Resumo: Background: Insulin is a hormone that regulates blood glucose homeostasis and is a central protein in a medical condition termed insulin injection amyloidosis. It is intimately associated with glycaemia and is vulnerable to glycation by glucose and other highly reactive carbonyls like methylglyoxal, especially in diabetic conditions. Protein glycation is involved in structure and stability changes that impair protein functionality, and is associated with several human diseases, such as diabetes and neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease and Familiar Amyloidotic Polyneuropathy. In the present work, methylglyoxal was investigated for their effects on the structure, stability and fibril formation of insulin.
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spelling Insulin glycation by methylglyoxal results in native-like aggregation and inhibition of fibril formationInsulinaBackground: Insulin is a hormone that regulates blood glucose homeostasis and is a central protein in a medical condition termed insulin injection amyloidosis. It is intimately associated with glycaemia and is vulnerable to glycation by glucose and other highly reactive carbonyls like methylglyoxal, especially in diabetic conditions. Protein glycation is involved in structure and stability changes that impair protein functionality, and is associated with several human diseases, such as diabetes and neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease and Familiar Amyloidotic Polyneuropathy. In the present work, methylglyoxal was investigated for their effects on the structure, stability and fibril formation of insulin.Results: Methylglyoxal was found to induce the formation of insulin native-like aggregates and reduce protein fibrillation by blocking the formation of the seeding nuclei. Equilibrium-unfolding experiments using chaotropic agents showed that glycated insulin has a small conformational stability and a weaker dependence on denaturant concentration (smaller m-value). Our observations suggest that methylglyoxal modification of insulin leads to a less compact and less stable structure that may be associated to an increased protein dynamics.Conclusions: We propose that higher dynamics in glycated insulin could prevent the formation of the rigid crossb core structure found in amyloid fibrils, thereby contributing to the reduction in the ability to form fibrils and to the population of different aggregation pathways like the formation of native-like aggregates.BioMed Central LtdRepositório ComumOliveira, Luis MALages, AnaGomes, Ricardo ANeves, HenriqueFamília, CarlosCoelho, Ana VQuintas, Alexandre2013-10-25T15:01:27Z20112011-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.26/4824engBMC Biochemistry 2011, 12:411471-209110.1186/1471-2091-12-41info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-08-03T02:30:50Zoai:comum.rcaap.pt:10400.26/4824Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T15:06:00.733007Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Insulin glycation by methylglyoxal results in native-like aggregation and inhibition of fibril formation
title Insulin glycation by methylglyoxal results in native-like aggregation and inhibition of fibril formation
spellingShingle Insulin glycation by methylglyoxal results in native-like aggregation and inhibition of fibril formation
Oliveira, Luis MA
Insulina
title_short Insulin glycation by methylglyoxal results in native-like aggregation and inhibition of fibril formation
title_full Insulin glycation by methylglyoxal results in native-like aggregation and inhibition of fibril formation
title_fullStr Insulin glycation by methylglyoxal results in native-like aggregation and inhibition of fibril formation
title_full_unstemmed Insulin glycation by methylglyoxal results in native-like aggregation and inhibition of fibril formation
title_sort Insulin glycation by methylglyoxal results in native-like aggregation and inhibition of fibril formation
author Oliveira, Luis MA
author_facet Oliveira, Luis MA
Lages, Ana
Gomes, Ricardo A
Neves, Henrique
Família, Carlos
Coelho, Ana V
Quintas, Alexandre
author_role author
author2 Lages, Ana
Gomes, Ricardo A
Neves, Henrique
Família, Carlos
Coelho, Ana V
Quintas, Alexandre
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Comum
dc.contributor.author.fl_str_mv Oliveira, Luis MA
Lages, Ana
Gomes, Ricardo A
Neves, Henrique
Família, Carlos
Coelho, Ana V
Quintas, Alexandre
dc.subject.por.fl_str_mv Insulina
topic Insulina
description Background: Insulin is a hormone that regulates blood glucose homeostasis and is a central protein in a medical condition termed insulin injection amyloidosis. It is intimately associated with glycaemia and is vulnerable to glycation by glucose and other highly reactive carbonyls like methylglyoxal, especially in diabetic conditions. Protein glycation is involved in structure and stability changes that impair protein functionality, and is associated with several human diseases, such as diabetes and neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease and Familiar Amyloidotic Polyneuropathy. In the present work, methylglyoxal was investigated for their effects on the structure, stability and fibril formation of insulin.
publishDate 2011
dc.date.none.fl_str_mv 2011
2011-01-01T00:00:00Z
2013-10-25T15:01:27Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.26/4824
url http://hdl.handle.net/10400.26/4824
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv BMC Biochemistry 2011, 12:41
1471-2091
10.1186/1471-2091-12-41
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central Ltd
publisher.none.fl_str_mv BioMed Central Ltd
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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