Human apolipoprotein A-I Gly26Arg stimulation of inflammatory responses via NF-kB activation: Potential roles in amyloidosis?

Autores
Ramella, Nahuel; Andújar, Isabel; Ríos, José Luis; Rosu, Silvana Antonia; Tricerri, Maria Alejandra; Schinella, Guillermo Raúl
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The cascade of molecular events leading to Human apolipoprotein A–I (apoA–I) amyloidosis is not completely understood, not even the pathways that determine clinical manifestations associated to systemic protein deposition in organs such as liver, kidney and heart. About twenty natural variants of apoA–I were described as inducing amyloidosis, but the mechanisms driving their aggregation and deposition are still unclear. We previously identified that the mutant Gly26Arg but not Lys107-0 induced the release of cytokines and reactive oxygen species from cultured RAW 264.7 murine macrophages, suggesting that part of the pathogenic pathway could elicit of an inflammatory signal. In this work we gained deep insight into this mechanism and determined that Gly26Arg induced a specific pro-inflammatory cascade involving activation of NF-κB and its translocation into the nucleus. These findings suggest that some but not all apoA–I natural variants might promote a pro-oxidant microenvironment which could in turn result in oxidative processing of the variants into a misfolded conformation.
Fil: Ramella, Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Andújar, Isabel. Fundación Hospital Universitario Dr. Peset; España. Universidad de Valencia; España
Fil: Ríos, José Luis. Universidad de Valencia; España. Fundación Hospital Universitario Dr. Peset; España
Fil: Rosu, Silvana Antonia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Tricerri, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Schinella, Guillermo Raúl. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina
Materia
AMYLOIDOSIS
APOLIPOPROTEIN A-I VARIANTS
INFLAMMATION
MACROPHAGES ACTIVATION
NUCLEAR FACTOR-ΚB
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:11336/96201

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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Human apolipoprotein A-I Gly26Arg stimulation of inflammatory responses via NF-kB activation: Potential roles in amyloidosis?Ramella, NahuelAndújar, IsabelRíos, José LuisRosu, Silvana AntoniaTricerri, Maria AlejandraSchinella, Guillermo RaúlAMYLOIDOSISAPOLIPOPROTEIN A-I VARIANTSINFLAMMATIONMACROPHAGES ACTIVATIONNUCLEAR FACTOR-ΚBhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The cascade of molecular events leading to Human apolipoprotein A–I (apoA–I) amyloidosis is not completely understood, not even the pathways that determine clinical manifestations associated to systemic protein deposition in organs such as liver, kidney and heart. About twenty natural variants of apoA–I were described as inducing amyloidosis, but the mechanisms driving their aggregation and deposition are still unclear. We previously identified that the mutant Gly26Arg but not Lys107-0 induced the release of cytokines and reactive oxygen species from cultured RAW 264.7 murine macrophages, suggesting that part of the pathogenic pathway could elicit of an inflammatory signal. In this work we gained deep insight into this mechanism and determined that Gly26Arg induced a specific pro-inflammatory cascade involving activation of NF-κB and its translocation into the nucleus. These findings suggest that some but not all apoA–I natural variants might promote a pro-oxidant microenvironment which could in turn result in oxidative processing of the variants into a misfolded conformation.Fil: Ramella, Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Andújar, Isabel. Fundación Hospital Universitario Dr. Peset; España. Universidad de Valencia; EspañaFil: Ríos, José Luis. Universidad de Valencia; España. Fundación Hospital Universitario Dr. Peset; EspañaFil: Rosu, Silvana Antonia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Tricerri, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Schinella, Guillermo Raúl. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; ArgentinaElsevier2018-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/96201Ramella, Nahuel; Andújar, Isabel; Ríos, José Luis; Rosu, Silvana Antonia; Tricerri, Maria Alejandra; et al.; Human apolipoprotein A-I Gly26Arg stimulation of inflammatory responses via NF-kB activation: Potential roles in amyloidosis?; Elsevier; Pathophysiology (amsterdam); 25; 4; 12-2018; 397-4040928-4680CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0928468018300993info:eu-repo/semantics/altIdentifier/doi/10.1016/j.pathophys.2018.08.002info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:38:36Zoai:ri.conicet.gov.ar:11336/96201instacron: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:34982025-10-15 14:38:36.669CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Human apolipoprotein A-I Gly26Arg stimulation of inflammatory responses via NF-kB activation: Potential roles in amyloidosis?
title Human apolipoprotein A-I Gly26Arg stimulation of inflammatory responses via NF-kB activation: Potential roles in amyloidosis?
spellingShingle Human apolipoprotein A-I Gly26Arg stimulation of inflammatory responses via NF-kB activation: Potential roles in amyloidosis?
Ramella, Nahuel
AMYLOIDOSIS
APOLIPOPROTEIN A-I VARIANTS
INFLAMMATION
MACROPHAGES ACTIVATION
NUCLEAR FACTOR-ΚB
title_short Human apolipoprotein A-I Gly26Arg stimulation of inflammatory responses via NF-kB activation: Potential roles in amyloidosis?
title_full Human apolipoprotein A-I Gly26Arg stimulation of inflammatory responses via NF-kB activation: Potential roles in amyloidosis?
title_fullStr Human apolipoprotein A-I Gly26Arg stimulation of inflammatory responses via NF-kB activation: Potential roles in amyloidosis?
title_full_unstemmed Human apolipoprotein A-I Gly26Arg stimulation of inflammatory responses via NF-kB activation: Potential roles in amyloidosis?
title_sort Human apolipoprotein A-I Gly26Arg stimulation of inflammatory responses via NF-kB activation: Potential roles in amyloidosis?
dc.creator.none.fl_str_mv Ramella, Nahuel
Andújar, Isabel
Ríos, José Luis
Rosu, Silvana Antonia
Tricerri, Maria Alejandra
Schinella, Guillermo Raúl
author Ramella, Nahuel
author_facet Ramella, Nahuel
Andújar, Isabel
Ríos, José Luis
Rosu, Silvana Antonia
Tricerri, Maria Alejandra
Schinella, Guillermo Raúl
author_role author
author2 Andújar, Isabel
Ríos, José Luis
Rosu, Silvana Antonia
Tricerri, Maria Alejandra
Schinella, Guillermo Raúl
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv AMYLOIDOSIS
APOLIPOPROTEIN A-I VARIANTS
INFLAMMATION
MACROPHAGES ACTIVATION
NUCLEAR FACTOR-ΚB
topic AMYLOIDOSIS
APOLIPOPROTEIN A-I VARIANTS
INFLAMMATION
MACROPHAGES ACTIVATION
NUCLEAR FACTOR-ΚB
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 cascade of molecular events leading to Human apolipoprotein A–I (apoA–I) amyloidosis is not completely understood, not even the pathways that determine clinical manifestations associated to systemic protein deposition in organs such as liver, kidney and heart. About twenty natural variants of apoA–I were described as inducing amyloidosis, but the mechanisms driving their aggregation and deposition are still unclear. We previously identified that the mutant Gly26Arg but not Lys107-0 induced the release of cytokines and reactive oxygen species from cultured RAW 264.7 murine macrophages, suggesting that part of the pathogenic pathway could elicit of an inflammatory signal. In this work we gained deep insight into this mechanism and determined that Gly26Arg induced a specific pro-inflammatory cascade involving activation of NF-κB and its translocation into the nucleus. These findings suggest that some but not all apoA–I natural variants might promote a pro-oxidant microenvironment which could in turn result in oxidative processing of the variants into a misfolded conformation.
Fil: Ramella, Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Andújar, Isabel. Fundación Hospital Universitario Dr. Peset; España. Universidad de Valencia; España
Fil: Ríos, José Luis. Universidad de Valencia; España. Fundación Hospital Universitario Dr. Peset; España
Fil: Rosu, Silvana Antonia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Tricerri, Maria Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentina
Fil: Schinella, Guillermo Raúl. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina
description The cascade of molecular events leading to Human apolipoprotein A–I (apoA–I) amyloidosis is not completely understood, not even the pathways that determine clinical manifestations associated to systemic protein deposition in organs such as liver, kidney and heart. About twenty natural variants of apoA–I were described as inducing amyloidosis, but the mechanisms driving their aggregation and deposition are still unclear. We previously identified that the mutant Gly26Arg but not Lys107-0 induced the release of cytokines and reactive oxygen species from cultured RAW 264.7 murine macrophages, suggesting that part of the pathogenic pathway could elicit of an inflammatory signal. In this work we gained deep insight into this mechanism and determined that Gly26Arg induced a specific pro-inflammatory cascade involving activation of NF-κB and its translocation into the nucleus. These findings suggest that some but not all apoA–I natural variants might promote a pro-oxidant microenvironment which could in turn result in oxidative processing of the variants into a misfolded conformation.
publishDate 2018
dc.date.none.fl_str_mv 2018-12
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/11336/96201
Ramella, Nahuel; Andújar, Isabel; Ríos, José Luis; Rosu, Silvana Antonia; Tricerri, Maria Alejandra; et al.; Human apolipoprotein A-I Gly26Arg stimulation of inflammatory responses via NF-kB activation: Potential roles in amyloidosis?; Elsevier; Pathophysiology (amsterdam); 25; 4; 12-2018; 397-404
0928-4680
CONICET Digital
CONICET
url http://hdl.handle.net/11336/96201
identifier_str_mv Ramella, Nahuel; Andújar, Isabel; Ríos, José Luis; Rosu, Silvana Antonia; Tricerri, Maria Alejandra; et al.; Human apolipoprotein A-I Gly26Arg stimulation of inflammatory responses via NF-kB activation: Potential roles in amyloidosis?; Elsevier; Pathophysiology (amsterdam); 25; 4; 12-2018; 397-404
0928-4680
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.sciencedirect.com/science/article/pii/S0928468018300993
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.pathophys.2018.08.002
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
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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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