Papel de la nueva familia de receptores endolisosomales de NAADP (TPCs) en la función cardiovascular y la fisiopatología del síndrome metabólico

Rationale: Autophagy participates in both physiological and pathological remodeling of the heart. The endolysosomal two-pore channels TPC1 and TPC2 have been implicated in the regulation of metabolism and autophagy. Objective: To study the role of TPC1 and TPC2 in cardiac metabolism and in basal and...

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Autor: García Rúa, Vanessa
Tipo de recurso: tesis doctoral
Fecha de publicación:2016
País:España
Institución:Universidad de Santiago de Compostela (USC)
Repositorio:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Idioma:español
OAI Identifier:oai:minerva.usc.gal:10347/13847
Acceso en línea:http://hdl.handle.net/10347/13847
Access Level:acceso abierto
Palabra clave:Materias::Investigación::32 Ciencias médicas::3205 Medicina interna::320502 Endocrinología
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spelling Papel de la nueva familia de receptores endolisosomales de NAADP (TPCs) en la función cardiovascular y la fisiopatología del síndrome metabólicoGarcía Rúa, VanessaMaterias::Investigación::32 Ciencias médicas::3205 Medicina interna::320502 EndocrinologíaRationale: Autophagy participates in both physiological and pathological remodeling of the heart. The endolysosomal two-pore channels TPC1 and TPC2 have been implicated in the regulation of metabolism and autophagy. Objective: To study the role of TPC1 and TPC2 in cardiac metabolism and in basal and induced cardiac autophagic activity. Methods and Results: The cardiac tissue of TPC1 knockout mice showed significative alterations in key proteins related with cardiac metabolism as well as with cardiac contraction and/or structure maintenance. siRNA depletion of TPC1 induced an increase in glucose uptake and on GLUT-4 translocation in cultured cardiomyocytes. In addition, starvation induced a significant increase in TPC1 and TPC2 transcripts and protein levels that paralleled the increase in autophagic flux (identified by increased LC3-II and decreased p62 levels) in cultured cardiomyocytes. SiRNA depletion of TPC2 alone or together with TPC1 increased both LC3-II and p62 levels under basal conditions and in response to starvation, suggesting a change in the autophagic process. Electron micrographs of cardiac tissue from TPC1/2 double knockout mice showed that cardiomyocytes contained large numbers of immature lysosomes with diameters significantly smaller than those of wild-type mice. In cardiac tissues from both humans and rats, TPC1 and TPC2 transcripts and protein levels were higher in females than in males and increased in heart failure patients compared to healthy controls. Conclusions: These data are the first evidence showing that the TPCs and the endolysosomal system could be involved in cardiac metabolism, cardiac autophagy, and thus, in the physiopathology of cardiovascular diseases.Lago Paz, María FranciscaGonzález Juanatey, José RamónUniversidade de Santiago de Compostela. Facultade de Medicina e Odontoloxía.Facultade de Bioloxía. Departamento de Medicina. Laboratorio de Investigación en Cardioloxía Celular e Molecular do Instituto de Investigacións Sanitarias20162016-02-1620162016-02-16doctoral thesishttp://purl.org/coar/resource_type/c_db06info:eu-repo/semantics/doctoralThesisapplication/pdfhttp://hdl.handle.net/10347/13847reponame:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostelainstname:Universidad de Santiago de Compostela (USC)Españolspaopen accesshttp://purl.org/coar/access_right/c_abf2Esta obra atópase baixo unha licenza internacional Creative Commons BY-NC-ND 4.0. Calquera forma de reprodución, distribución, comunicación pública ou transformación desta obra non incluída na licenza Creative Commons BY-NC-ND 4.0 só pode ser realizada coa autorización expresa dos titulares, salvo excepción prevista pola lei. Pode acceder Vde. ao texto completo da licenza nesta ligazón: https://creativecommons.org/licenses/by-nc-nd/4.0/deed.glhttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.glinfo:eu-repo/semantics/openAccessoai:minerva.usc.gal:10347/138472026-06-15T12:47:27Z
dc.title.none.fl_str_mv Papel de la nueva familia de receptores endolisosomales de NAADP (TPCs) en la función cardiovascular y la fisiopatología del síndrome metabólico
title Papel de la nueva familia de receptores endolisosomales de NAADP (TPCs) en la función cardiovascular y la fisiopatología del síndrome metabólico
spellingShingle Papel de la nueva familia de receptores endolisosomales de NAADP (TPCs) en la función cardiovascular y la fisiopatología del síndrome metabólico
García Rúa, Vanessa
Materias::Investigación::32 Ciencias médicas::3205 Medicina interna::320502 Endocrinología
title_short Papel de la nueva familia de receptores endolisosomales de NAADP (TPCs) en la función cardiovascular y la fisiopatología del síndrome metabólico
title_full Papel de la nueva familia de receptores endolisosomales de NAADP (TPCs) en la función cardiovascular y la fisiopatología del síndrome metabólico
title_fullStr Papel de la nueva familia de receptores endolisosomales de NAADP (TPCs) en la función cardiovascular y la fisiopatología del síndrome metabólico
title_full_unstemmed Papel de la nueva familia de receptores endolisosomales de NAADP (TPCs) en la función cardiovascular y la fisiopatología del síndrome metabólico
title_sort Papel de la nueva familia de receptores endolisosomales de NAADP (TPCs) en la función cardiovascular y la fisiopatología del síndrome metabólico
dc.creator.none.fl_str_mv García Rúa, Vanessa
author García Rúa, Vanessa
author_facet García Rúa, Vanessa
author_role author
dc.contributor.none.fl_str_mv Lago Paz, María Francisca
González Juanatey, José Ramón
Universidade de Santiago de Compostela. Facultade de Medicina e Odontoloxía.Facultade de Bioloxía. Departamento de Medicina. Laboratorio de Investigación en Cardioloxía Celular e Molecular do Instituto de Investigacións Sanitarias
dc.subject.none.fl_str_mv Materias::Investigación::32 Ciencias médicas::3205 Medicina interna::320502 Endocrinología
topic Materias::Investigación::32 Ciencias médicas::3205 Medicina interna::320502 Endocrinología
description Rationale: Autophagy participates in both physiological and pathological remodeling of the heart. The endolysosomal two-pore channels TPC1 and TPC2 have been implicated in the regulation of metabolism and autophagy. Objective: To study the role of TPC1 and TPC2 in cardiac metabolism and in basal and induced cardiac autophagic activity. Methods and Results: The cardiac tissue of TPC1 knockout mice showed significative alterations in key proteins related with cardiac metabolism as well as with cardiac contraction and/or structure maintenance. siRNA depletion of TPC1 induced an increase in glucose uptake and on GLUT-4 translocation in cultured cardiomyocytes. In addition, starvation induced a significant increase in TPC1 and TPC2 transcripts and protein levels that paralleled the increase in autophagic flux (identified by increased LC3-II and decreased p62 levels) in cultured cardiomyocytes. SiRNA depletion of TPC2 alone or together with TPC1 increased both LC3-II and p62 levels under basal conditions and in response to starvation, suggesting a change in the autophagic process. Electron micrographs of cardiac tissue from TPC1/2 double knockout mice showed that cardiomyocytes contained large numbers of immature lysosomes with diameters significantly smaller than those of wild-type mice. In cardiac tissues from both humans and rats, TPC1 and TPC2 transcripts and protein levels were higher in females than in males and increased in heart failure patients compared to healthy controls. Conclusions: These data are the first evidence showing that the TPCs and the endolysosomal system could be involved in cardiac metabolism, cardiac autophagy, and thus, in the physiopathology of cardiovascular diseases.
publishDate 2016
dc.date.none.fl_str_mv 2016
2016-02-16
2016
2016-02-16
dc.type.none.fl_str_mv doctoral thesis
http://purl.org/coar/resource_type/c_db06
dc.type.openaire.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
dc.identifier.none.fl_str_mv http://hdl.handle.net/10347/13847
url http://hdl.handle.net/10347/13847
dc.language.none.fl_str_mv Español
spa
language_invalid_str_mv Español
language spa
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.gl
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.gl
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
instname:Universidad de Santiago de Compostela (USC)
instname_str Universidad de Santiago de Compostela (USC)
reponame_str Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
collection Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
repository.name.fl_str_mv
repository.mail.fl_str_mv
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