Higher apoptotic state in Fabry disease peripheral blood mononuclear cells: effect of globotriaosylceramide

Autores
de Francesco, Pablo Nicolás; Mucci, Juan Marcos; Ceci, Romina; Fossati, Carlos Alberto; Rozenfeld, Paula Adriana
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Fabry disease is an X-linked lysosomal storage disorder (LSD) due to deficiency of the enzyme α-galactosidase A, resulting in intracellular deposition of globotriaosylceramide (Gb3). Accumulation of Gb3 is probably related to tissue and organ dysfunctions. Diverse pathological mechanisms are elicited in LSDs, giving together the phenotypic expression of each disease. The purpose of the present study is to investigate if apoptosis could play a role in Fabry disease pathogenesis and to understand the mechanisms involved in the proapoptotic state. We have demonstrated that Fabry disease peripheral blood mononuclear cells display a higher apoptotic state, which is reduced by enzyme replacement therapy (ERT), and is mediated, at least in part, by activation of the intrinsic pathway of caspases. We could rule out the implication of “unfolded protein response-ER stress” in this apoptotic process. To further confirm the suggestion that Gb3 is associated to apoptotic cell death, we treated normal cells with Gb3 at concentrations found in Fabry patients. Addition of Gb3 resulted in a dose-dependent induction of apoptosis involving the intrinsic pathway. In summary, PBMC from Fabry patients display a higher apoptotic state, which could be mainly related to elevated Gb3.
Fil: de Francesco, Pablo Nicolás. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mucci, Juan Marcos. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ceci, Romina. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina
Fil: Fossati, Carlos Alberto. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rozenfeld, Paula Adriana. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Fabry Disease
Globotriaosylceramide
Apoptosis
Enzyme Replacement Treatment
Pathogenesis
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/13787
Acceder
id CONICETDig_5511515edb5d1fd3cd315ae7d46d7727
oai_identifier_str oai:ri.conicet.gov.ar:11336/13787
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Higher apoptotic state in Fabry disease peripheral blood mononuclear cells: effect of globotriaosylceramidede Francesco, Pablo NicolásMucci, Juan MarcosCeci, RominaFossati, Carlos AlbertoRozenfeld, Paula AdrianaFabry DiseaseGlobotriaosylceramideApoptosisEnzyme Replacement TreatmentPathogenesishttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Fabry disease is an X-linked lysosomal storage disorder (LSD) due to deficiency of the enzyme α-galactosidase A, resulting in intracellular deposition of globotriaosylceramide (Gb3). Accumulation of Gb3 is probably related to tissue and organ dysfunctions. Diverse pathological mechanisms are elicited in LSDs, giving together the phenotypic expression of each disease. The purpose of the present study is to investigate if apoptosis could play a role in Fabry disease pathogenesis and to understand the mechanisms involved in the proapoptotic state. We have demonstrated that Fabry disease peripheral blood mononuclear cells display a higher apoptotic state, which is reduced by enzyme replacement therapy (ERT), and is mediated, at least in part, by activation of the intrinsic pathway of caspases. We could rule out the implication of “unfolded protein response-ER stress” in this apoptotic process. To further confirm the suggestion that Gb3 is associated to apoptotic cell death, we treated normal cells with Gb3 at concentrations found in Fabry patients. Addition of Gb3 resulted in a dose-dependent induction of apoptosis involving the intrinsic pathway. In summary, PBMC from Fabry patients display a higher apoptotic state, which could be mainly related to elevated Gb3.Fil: de Francesco, Pablo Nicolás. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mucci, Juan Marcos. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ceci, Romina. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Laboratorio de Investigaciones del Sistema Inmune; ArgentinaFil: Fossati, Carlos Alberto. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rozenfeld, Paula Adriana. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier Inc2011-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/13787de Francesco, Pablo Nicolás; Mucci, Juan Marcos; Ceci, Romina; Fossati, Carlos Alberto; Rozenfeld, Paula Adriana; Higher apoptotic state in Fabry disease peripheral blood mononuclear cells: effect of globotriaosylceramide; Elsevier Inc; Molecular Genetics And Metabolism; 104; 3; 11-2011; 319-3241096-7192enginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ymgme.2011.06.007info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1096719211001946info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:30:52Zoai:ri.conicet.gov.ar:11336/13787instacron: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:34982025-09-29 10:30:52.378CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Higher apoptotic state in Fabry disease peripheral blood mononuclear cells: effect of globotriaosylceramide
title Higher apoptotic state in Fabry disease peripheral blood mononuclear cells: effect of globotriaosylceramide
spellingShingle Higher apoptotic state in Fabry disease peripheral blood mononuclear cells: effect of globotriaosylceramide
de Francesco, Pablo Nicolás
Fabry Disease
Globotriaosylceramide
Apoptosis
Enzyme Replacement Treatment
Pathogenesis
title_short Higher apoptotic state in Fabry disease peripheral blood mononuclear cells: effect of globotriaosylceramide
title_full Higher apoptotic state in Fabry disease peripheral blood mononuclear cells: effect of globotriaosylceramide
title_fullStr Higher apoptotic state in Fabry disease peripheral blood mononuclear cells: effect of globotriaosylceramide
title_full_unstemmed Higher apoptotic state in Fabry disease peripheral blood mononuclear cells: effect of globotriaosylceramide
title_sort Higher apoptotic state in Fabry disease peripheral blood mononuclear cells: effect of globotriaosylceramide
dc.creator.none.fl_str_mv de Francesco, Pablo Nicolás
Mucci, Juan Marcos
Ceci, Romina
Fossati, Carlos Alberto
Rozenfeld, Paula Adriana
author de Francesco, Pablo Nicolás
author_facet de Francesco, Pablo Nicolás
Mucci, Juan Marcos
Ceci, Romina
Fossati, Carlos Alberto
Rozenfeld, Paula Adriana
author_role author
author2 Mucci, Juan Marcos
Ceci, Romina
Fossati, Carlos Alberto
Rozenfeld, Paula Adriana
author2_role author
author
author
author
dc.subject.none.fl_str_mv Fabry Disease
Globotriaosylceramide
Apoptosis
Enzyme Replacement Treatment
Pathogenesis
topic Fabry Disease
Globotriaosylceramide
Apoptosis
Enzyme Replacement Treatment
Pathogenesis
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Fabry disease is an X-linked lysosomal storage disorder (LSD) due to deficiency of the enzyme α-galactosidase A, resulting in intracellular deposition of globotriaosylceramide (Gb3). Accumulation of Gb3 is probably related to tissue and organ dysfunctions. Diverse pathological mechanisms are elicited in LSDs, giving together the phenotypic expression of each disease. The purpose of the present study is to investigate if apoptosis could play a role in Fabry disease pathogenesis and to understand the mechanisms involved in the proapoptotic state. We have demonstrated that Fabry disease peripheral blood mononuclear cells display a higher apoptotic state, which is reduced by enzyme replacement therapy (ERT), and is mediated, at least in part, by activation of the intrinsic pathway of caspases. We could rule out the implication of “unfolded protein response-ER stress” in this apoptotic process. To further confirm the suggestion that Gb3 is associated to apoptotic cell death, we treated normal cells with Gb3 at concentrations found in Fabry patients. Addition of Gb3 resulted in a dose-dependent induction of apoptosis involving the intrinsic pathway. In summary, PBMC from Fabry patients display a higher apoptotic state, which could be mainly related to elevated Gb3.
Fil: de Francesco, Pablo Nicolás. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Mucci, Juan Marcos. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ceci, Romina. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina
Fil: Fossati, Carlos Alberto. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rozenfeld, Paula Adriana. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Fabry disease is an X-linked lysosomal storage disorder (LSD) due to deficiency of the enzyme α-galactosidase A, resulting in intracellular deposition of globotriaosylceramide (Gb3). Accumulation of Gb3 is probably related to tissue and organ dysfunctions. Diverse pathological mechanisms are elicited in LSDs, giving together the phenotypic expression of each disease. The purpose of the present study is to investigate if apoptosis could play a role in Fabry disease pathogenesis and to understand the mechanisms involved in the proapoptotic state. We have demonstrated that Fabry disease peripheral blood mononuclear cells display a higher apoptotic state, which is reduced by enzyme replacement therapy (ERT), and is mediated, at least in part, by activation of the intrinsic pathway of caspases. We could rule out the implication of “unfolded protein response-ER stress” in this apoptotic process. To further confirm the suggestion that Gb3 is associated to apoptotic cell death, we treated normal cells with Gb3 at concentrations found in Fabry patients. Addition of Gb3 resulted in a dose-dependent induction of apoptosis involving the intrinsic pathway. In summary, PBMC from Fabry patients display a higher apoptotic state, which could be mainly related to elevated Gb3.
publishDate 2011
dc.date.none.fl_str_mv 2011-11
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/11336/13787
de Francesco, Pablo Nicolás; Mucci, Juan Marcos; Ceci, Romina; Fossati, Carlos Alberto; Rozenfeld, Paula Adriana; Higher apoptotic state in Fabry disease peripheral blood mononuclear cells: effect of globotriaosylceramide; Elsevier Inc; Molecular Genetics And Metabolism; 104; 3; 11-2011; 319-324
1096-7192
url http://hdl.handle.net/11336/13787
identifier_str_mv de Francesco, Pablo Nicolás; Mucci, Juan Marcos; Ceci, Romina; Fossati, Carlos Alberto; Rozenfeld, Paula Adriana; Higher apoptotic state in Fabry disease peripheral blood mononuclear cells: effect of globotriaosylceramide; Elsevier Inc; Molecular Genetics And Metabolism; 104; 3; 11-2011; 319-324
1096-7192
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ymgme.2011.06.007
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1096719211001946
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Inc
publisher.none.fl_str_mv Elsevier Inc
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 13.070432

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