LRP1-Mediated AggLDL endocytosis promotes pholesteryl ester accumulation and impairs insulin response in HL-1 cells

Autores
Actis Dato, Virginia; Benitez Amaro, Aleyda; de Gonzalo Calvo, David; Vazquez, Matias Maximiliano; Bonacci, Gustavo Roberto; Llorente Cortés, Vicenta; Chiabrando, Gustavo Alberto
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The cardiovascular disease (CVD) frequently developed during metabolic syndrome and type-2 diabetes mellitus is associated with increased levels of aggregation-prone small LDL particles. Aggregated LDL (aggLDL) internalization is mediated by low-density lipoprotein receptor-related protein-1 (LRP1) promoting intracellular cholesteryl ester (CE) accumulation. Additionally, LRP1 plays a key function in the regulation of insulin receptor (IR) and glucose transporter type 4 (GLUT4) activities. Nevertheless, the link between LRP1, CE accumulation, and insulin response has not been previously studied in cardiomyocytes. We aimed to identify mechanisms through which aggLDL, by its interaction with LRP1, produce CE accumulation and affects the insulin-induced intracellular signaling and GLUT4 trafficking in HL-1 cells. We demonstrated that LRP1 mediates the endocytosis of aggLDL and promotes CE accumulation in these cells. Moreover, aggLDL reduced the molecular association between IR and LRP1 and impaired insulin-induced intracellular signaling activation. Finally, aggLDL affected GLUT4 translocation to the plasma membrane and the 2-NBDG uptake in insulin-stimulated cells. We conclude that LRP1 is a key regulator of the insulin response, which can be altered by CE accumulation through LRP1-mediated aggLDL endocytosis.
Fil: Actis Dato, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Benitez Amaro, Aleyda. Institute of Biomedical Research of Barcelona; España. Biomedical Research Institute Sant Pau; España
Fil: de Gonzalo Calvo, David. Institute of Biomedical Research of Barcelona; España. Biomedical Research Institute Sant Pau; España. Institute of Health Carlos III; España
Fil: Vazquez, Matias Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Institute of Biomedical Research of Barcelona; España
Fil: Bonacci, Gustavo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina
Fil: Llorente Cortés, Vicenta. Institute of Biomedical Research of Barcelona; España. Institute of Health Carlos III; España. Biomedical Research Institute Sant Pau; España
Fil: Chiabrando, Gustavo Alberto. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Materia
LRP1
CARDIOVASCULAR DISEASE
GLUCOSE
LIPIDS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/158917
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/158917
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling LRP1-Mediated AggLDL endocytosis promotes pholesteryl ester accumulation and impairs insulin response in HL-1 cellsActis Dato, VirginiaBenitez Amaro, Aleydade Gonzalo Calvo, DavidVazquez, Matias MaximilianoBonacci, Gustavo RobertoLlorente Cortés, VicentaChiabrando, Gustavo AlbertoLRP1CARDIOVASCULAR DISEASEGLUCOSELIPIDShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The cardiovascular disease (CVD) frequently developed during metabolic syndrome and type-2 diabetes mellitus is associated with increased levels of aggregation-prone small LDL particles. Aggregated LDL (aggLDL) internalization is mediated by low-density lipoprotein receptor-related protein-1 (LRP1) promoting intracellular cholesteryl ester (CE) accumulation. Additionally, LRP1 plays a key function in the regulation of insulin receptor (IR) and glucose transporter type 4 (GLUT4) activities. Nevertheless, the link between LRP1, CE accumulation, and insulin response has not been previously studied in cardiomyocytes. We aimed to identify mechanisms through which aggLDL, by its interaction with LRP1, produce CE accumulation and affects the insulin-induced intracellular signaling and GLUT4 trafficking in HL-1 cells. We demonstrated that LRP1 mediates the endocytosis of aggLDL and promotes CE accumulation in these cells. Moreover, aggLDL reduced the molecular association between IR and LRP1 and impaired insulin-induced intracellular signaling activation. Finally, aggLDL affected GLUT4 translocation to the plasma membrane and the 2-NBDG uptake in insulin-stimulated cells. We conclude that LRP1 is a key regulator of the insulin response, which can be altered by CE accumulation through LRP1-mediated aggLDL endocytosis.Fil: Actis Dato, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Benitez Amaro, Aleyda. Institute of Biomedical Research of Barcelona; España. Biomedical Research Institute Sant Pau; EspañaFil: de Gonzalo Calvo, David. Institute of Biomedical Research of Barcelona; España. Biomedical Research Institute Sant Pau; España. Institute of Health Carlos III; EspañaFil: Vazquez, Matias Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Institute of Biomedical Research of Barcelona; EspañaFil: Bonacci, Gustavo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; ArgentinaFil: Llorente Cortés, Vicenta. Institute of Biomedical Research of Barcelona; España. Institute of Health Carlos III; España. Biomedical Research Institute Sant Pau; EspañaFil: Chiabrando, Gustavo Alberto. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaMDPI2020-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/158917Actis Dato, Virginia; Benitez Amaro, Aleyda; de Gonzalo Calvo, David; Vazquez, Matias Maximiliano; Bonacci, Gustavo Roberto; et al.; LRP1-Mediated AggLDL endocytosis promotes pholesteryl ester accumulation and impairs insulin response in HL-1 cells; MDPI; Cells; 9; 1; 1-2020; 1-182073-4409CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2073-4409/9/1/182info:eu-repo/semantics/altIdentifier/doi/10.3390/cells9010182info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:02:19Zoai:ri.conicet.gov.ar:11336/158917instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:02:20.129CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv LRP1-Mediated AggLDL endocytosis promotes pholesteryl ester accumulation and impairs insulin response in HL-1 cells
title LRP1-Mediated AggLDL endocytosis promotes pholesteryl ester accumulation and impairs insulin response in HL-1 cells
spellingShingle LRP1-Mediated AggLDL endocytosis promotes pholesteryl ester accumulation and impairs insulin response in HL-1 cells
Actis Dato, Virginia
LRP1
CARDIOVASCULAR DISEASE
GLUCOSE
LIPIDS
title_short LRP1-Mediated AggLDL endocytosis promotes pholesteryl ester accumulation and impairs insulin response in HL-1 cells
title_full LRP1-Mediated AggLDL endocytosis promotes pholesteryl ester accumulation and impairs insulin response in HL-1 cells
title_fullStr LRP1-Mediated AggLDL endocytosis promotes pholesteryl ester accumulation and impairs insulin response in HL-1 cells
title_full_unstemmed LRP1-Mediated AggLDL endocytosis promotes pholesteryl ester accumulation and impairs insulin response in HL-1 cells
title_sort LRP1-Mediated AggLDL endocytosis promotes pholesteryl ester accumulation and impairs insulin response in HL-1 cells
dc.creator.none.fl_str_mv Actis Dato, Virginia
Benitez Amaro, Aleyda
de Gonzalo Calvo, David
Vazquez, Matias Maximiliano
Bonacci, Gustavo Roberto
Llorente Cortés, Vicenta
Chiabrando, Gustavo Alberto
author Actis Dato, Virginia
author_facet Actis Dato, Virginia
Benitez Amaro, Aleyda
de Gonzalo Calvo, David
Vazquez, Matias Maximiliano
Bonacci, Gustavo Roberto
Llorente Cortés, Vicenta
Chiabrando, Gustavo Alberto
author_role author
author2 Benitez Amaro, Aleyda
de Gonzalo Calvo, David
Vazquez, Matias Maximiliano
Bonacci, Gustavo Roberto
Llorente Cortés, Vicenta
Chiabrando, Gustavo Alberto
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv LRP1
CARDIOVASCULAR DISEASE
GLUCOSE
LIPIDS
topic LRP1
CARDIOVASCULAR DISEASE
GLUCOSE
LIPIDS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The cardiovascular disease (CVD) frequently developed during metabolic syndrome and type-2 diabetes mellitus is associated with increased levels of aggregation-prone small LDL particles. Aggregated LDL (aggLDL) internalization is mediated by low-density lipoprotein receptor-related protein-1 (LRP1) promoting intracellular cholesteryl ester (CE) accumulation. Additionally, LRP1 plays a key function in the regulation of insulin receptor (IR) and glucose transporter type 4 (GLUT4) activities. Nevertheless, the link between LRP1, CE accumulation, and insulin response has not been previously studied in cardiomyocytes. We aimed to identify mechanisms through which aggLDL, by its interaction with LRP1, produce CE accumulation and affects the insulin-induced intracellular signaling and GLUT4 trafficking in HL-1 cells. We demonstrated that LRP1 mediates the endocytosis of aggLDL and promotes CE accumulation in these cells. Moreover, aggLDL reduced the molecular association between IR and LRP1 and impaired insulin-induced intracellular signaling activation. Finally, aggLDL affected GLUT4 translocation to the plasma membrane and the 2-NBDG uptake in insulin-stimulated cells. We conclude that LRP1 is a key regulator of the insulin response, which can be altered by CE accumulation through LRP1-mediated aggLDL endocytosis.
Fil: Actis Dato, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Benitez Amaro, Aleyda. Institute of Biomedical Research of Barcelona; España. Biomedical Research Institute Sant Pau; España
Fil: de Gonzalo Calvo, David. Institute of Biomedical Research of Barcelona; España. Biomedical Research Institute Sant Pau; España. Institute of Health Carlos III; España
Fil: Vazquez, Matias Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Institute of Biomedical Research of Barcelona; España
Fil: Bonacci, Gustavo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina
Fil: Llorente Cortés, Vicenta. Institute of Biomedical Research of Barcelona; España. Institute of Health Carlos III; España. Biomedical Research Institute Sant Pau; España
Fil: Chiabrando, Gustavo Alberto. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
description The cardiovascular disease (CVD) frequently developed during metabolic syndrome and type-2 diabetes mellitus is associated with increased levels of aggregation-prone small LDL particles. Aggregated LDL (aggLDL) internalization is mediated by low-density lipoprotein receptor-related protein-1 (LRP1) promoting intracellular cholesteryl ester (CE) accumulation. Additionally, LRP1 plays a key function in the regulation of insulin receptor (IR) and glucose transporter type 4 (GLUT4) activities. Nevertheless, the link between LRP1, CE accumulation, and insulin response has not been previously studied in cardiomyocytes. We aimed to identify mechanisms through which aggLDL, by its interaction with LRP1, produce CE accumulation and affects the insulin-induced intracellular signaling and GLUT4 trafficking in HL-1 cells. We demonstrated that LRP1 mediates the endocytosis of aggLDL and promotes CE accumulation in these cells. Moreover, aggLDL reduced the molecular association between IR and LRP1 and impaired insulin-induced intracellular signaling activation. Finally, aggLDL affected GLUT4 translocation to the plasma membrane and the 2-NBDG uptake in insulin-stimulated cells. We conclude that LRP1 is a key regulator of the insulin response, which can be altered by CE accumulation through LRP1-mediated aggLDL endocytosis.
publishDate 2020
dc.date.none.fl_str_mv 2020-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/158917
Actis Dato, Virginia; Benitez Amaro, Aleyda; de Gonzalo Calvo, David; Vazquez, Matias Maximiliano; Bonacci, Gustavo Roberto; et al.; LRP1-Mediated AggLDL endocytosis promotes pholesteryl ester accumulation and impairs insulin response in HL-1 cells; MDPI; Cells; 9; 1; 1-2020; 1-18
2073-4409
CONICET Digital
CONICET
url http://hdl.handle.net/11336/158917
identifier_str_mv Actis Dato, Virginia; Benitez Amaro, Aleyda; de Gonzalo Calvo, David; Vazquez, Matias Maximiliano; Bonacci, Gustavo Roberto; et al.; LRP1-Mediated AggLDL endocytosis promotes pholesteryl ester accumulation and impairs insulin response in HL-1 cells; MDPI; Cells; 9; 1; 1-2020; 1-18
2073-4409
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2073-4409/9/1/182
info:eu-repo/semantics/altIdentifier/doi/10.3390/cells9010182
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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