Effects of vitamin K deficiency and its mechanisms in vertebrate's early development: zebrafish as a model

Detalhes bibliográficos
Autor(a) principal: Granadeiro, Luís Carlos Serrachino
Data de Publicação: 2015
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.1/7717
Resumo: Disertação de mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2015
id RCAP_8ae1071a7590837f15157d5607abc052
oai_identifier_str oai:sapientia.ualg.pt:10400.1/7717
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling Effects of vitamin K deficiency and its mechanisms in vertebrate's early development: zebrafish as a modelCiências biomédicasVitamina KVarfarinaPeixe-zebraEsqueletoExpressão génicaDomínio/Área Científica::Ciências Médicas::Ciências da SaúdeDisertação de mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2015Vitamin K (VK) acts as a cofactor of the enzyme γ-glutamyl carboxylase (Ggcx) promoting the γ-carboxylation of VK dependent proteins (VKDP), where a posttranslational conversion of Glu into Gla residues is achieved, providing calcium binding properties to VKDPs. Some VKDPs are involved in blood clotting but also in other processes. During γ-carboxylation, the reduced VK is converted to the epoxide form, which is then recycled back into VK by the enzyme VK epoxide reductase (Vkor). Warfarin inhibits Vkor activity, being used to control blood clotting through the reduction of the γ-carboxylation of coagulation factors in patients who are at risk of venous thromboembolism. However, it might affect the activity of other VKDP. When administered during pregnancy, it induces fetal morbidity and mortality in pregnant women, being this associated with bleeding disorders and skeletal deformities. In this work the effects of VK deficiency in vertebrate’s early development were evaluated using zebrafish (Danio rerio) as a model. Zebrafish (embryos and larvae) were exposed to increasing levels of warfarin (0, 5, 25 and 125 mg L-1) during two critical periods: 0-2.5 (embryonic development) and 2.5-5 (endotrophic larvae) days post fertilization. Larvae exposed to high concentrations of warfarin showed growth retardation, bleeding, underdeveloped swimbladder, pericardial inflammation, disruption of skeletogenesis, and increased mortality. The effects were much more severe when they were exposed to the anticoagulant during the embryonic stage. Regarding skeletogenesis, mineralization of several cranial structures as well as the axial skeleton was reduced. The length of the endochodral structures in the cranial region was also shorter in warfarin exposed larvae. Expression of genes involved in skeletogenesis (sox9, runx2, osx, col2a1, grp1, alp, mgp and bgp) was affected depending on the developmental stage analyzed. Present work brings new insights on the particular mechanisms by which warfarin (and thus, VK deficiency) affects chondrogenesis and osteoblastogenesis.Fernández, IgnacioGavaia, Paulo J.SapientiaGranadeiro, Luís Carlos Serrachino2017-02-19T01:30:09Z2015-12-1820152015-12-18T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10400.1/7717TID:201182335enginfo: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:RCAAP2023-07-24T10:18:52Zoai:sapientia.ualg.pt:10400.1/7717Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:00:01.437066Repositório 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 Effects of vitamin K deficiency and its mechanisms in vertebrate's early development: zebrafish as a model
title Effects of vitamin K deficiency and its mechanisms in vertebrate's early development: zebrafish as a model
spellingShingle Effects of vitamin K deficiency and its mechanisms in vertebrate's early development: zebrafish as a model
Granadeiro, Luís Carlos Serrachino
Ciências biomédicas
Vitamina K
Varfarina
Peixe-zebra
Esqueleto
Expressão génica
Domínio/Área Científica::Ciências Médicas::Ciências da Saúde
title_short Effects of vitamin K deficiency and its mechanisms in vertebrate's early development: zebrafish as a model
title_full Effects of vitamin K deficiency and its mechanisms in vertebrate's early development: zebrafish as a model
title_fullStr Effects of vitamin K deficiency and its mechanisms in vertebrate's early development: zebrafish as a model
title_full_unstemmed Effects of vitamin K deficiency and its mechanisms in vertebrate's early development: zebrafish as a model
title_sort Effects of vitamin K deficiency and its mechanisms in vertebrate's early development: zebrafish as a model
author Granadeiro, Luís Carlos Serrachino
author_facet Granadeiro, Luís Carlos Serrachino
author_role author
dc.contributor.none.fl_str_mv Fernández, Ignacio
Gavaia, Paulo J.
Sapientia
dc.contributor.author.fl_str_mv Granadeiro, Luís Carlos Serrachino
dc.subject.por.fl_str_mv Ciências biomédicas
Vitamina K
Varfarina
Peixe-zebra
Esqueleto
Expressão génica
Domínio/Área Científica::Ciências Médicas::Ciências da Saúde
topic Ciências biomédicas
Vitamina K
Varfarina
Peixe-zebra
Esqueleto
Expressão génica
Domínio/Área Científica::Ciências Médicas::Ciências da Saúde
description Disertação de mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2015
publishDate 2015
dc.date.none.fl_str_mv 2015-12-18
2015
2015-12-18T00:00:00Z
2017-02-19T01:30:09Z
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.uri.fl_str_mv http://hdl.handle.net/10400.1/7717
TID:201182335
url http://hdl.handle.net/10400.1/7717
identifier_str_mv TID:201182335
dc.language.iso.fl_str_mv eng
language eng
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.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
repository.mail.fl_str_mv
_version_ 1799133225052798976

Registros relacionados