Transcriptional regulation of insulin-degrading enzyme modulates mitochondrial amyloid β (Aβ) peptide catabolism and functionality

Autores
Leal, Maria Celeste; Magnani, Natalia Daniela; Villordo, Sergio; Marino, Cristina Ester; Evelson, Pablo Andres; Castaño, Eduardo Miguel; Morelli, Laura
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Studies of post-mortem brains from Alzheimer disease patients suggest that oxidative damage induced by mitochondrial amyloid β (mitAβ) accumulation is associated with mitochondrial dysfunction. However, the regulation of mitAβ metabolism is unknown. One of the proteases involved in mitAβ catabolism is the long insulin-degrading enzyme (IDE) isoform (IDE-Met(1)). However, the mechanisms of its expression are unknown, and its presence in brain is uncertain. We detected IDE-Met(1) in brain and showed that its expression is regulated by the mitochondrial biogenesis pathway (PGC-1α/NRF-1). A strong positive correlation between PGC-1α or NRF-1 and long IDE isoform transcripts was found in non-demented brains. This correlation was weaker in Alzheimer disease. In vitro inhibition of IDE increased mitAβ and impaired mitochondrial respiration. These changes were restored by inhibition of γ-secretase or promotion of mitochondrial biogenesis. Our results suggest that IDE-Met(1) links the mitochondrial biogenesis pathway with mitAβ levels and organelle functionality.
Fil: Leal, Maria Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Magnani, Natalia Daniela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Villordo, Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Marino, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Evelson, Pablo Andres. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Materia
Alzheimer disease
amyloid β peptide
insulin-degrading enzyme isoform
IDE
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:11336/19716
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/19716
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Transcriptional regulation of insulin-degrading enzyme modulates mitochondrial amyloid β (Aβ) peptide catabolism and functionalityLeal, Maria CelesteMagnani, Natalia DanielaVillordo, SergioMarino, Cristina EsterEvelson, Pablo AndresCastaño, Eduardo MiguelMorelli, LauraAlzheimer diseaseamyloid β peptideinsulin-degrading enzyme isoformIDEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Studies of post-mortem brains from Alzheimer disease patients suggest that oxidative damage induced by mitochondrial amyloid β (mitAβ) accumulation is associated with mitochondrial dysfunction. However, the regulation of mitAβ metabolism is unknown. One of the proteases involved in mitAβ catabolism is the long insulin-degrading enzyme (IDE) isoform (IDE-Met(1)). However, the mechanisms of its expression are unknown, and its presence in brain is uncertain. We detected IDE-Met(1) in brain and showed that its expression is regulated by the mitochondrial biogenesis pathway (PGC-1α/NRF-1). A strong positive correlation between PGC-1α or NRF-1 and long IDE isoform transcripts was found in non-demented brains. This correlation was weaker in Alzheimer disease. In vitro inhibition of IDE increased mitAβ and impaired mitochondrial respiration. These changes were restored by inhibition of γ-secretase or promotion of mitochondrial biogenesis. Our results suggest that IDE-Met(1) links the mitochondrial biogenesis pathway with mitAβ levels and organelle functionality.Fil: Leal, Maria Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Magnani, Natalia Daniela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Villordo, Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Marino, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Evelson, Pablo Andres. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaAmerican Society For Biochemistry And Molecular Biology2013-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/19716Leal, Maria Celeste; Magnani, Natalia Daniela; Villordo, Sergio; Marino, Cristina Ester; Evelson, Pablo Andres; et al.; Transcriptional regulation of insulin-degrading enzyme modulates mitochondrial amyloid β (Aβ) peptide catabolism and functionality; American Society For Biochemistry And Molecular Biology; Journal Of Biological Chemistry; 288; 18; 5-2013; 12920-129310021-92581083-351XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/288/18/12920.longinfo:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M112.424820info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:57:05Zoai:ri.conicet.gov.ar:11336/19716instacron: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 09:57:05.919CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Transcriptional regulation of insulin-degrading enzyme modulates mitochondrial amyloid β (Aβ) peptide catabolism and functionality
title Transcriptional regulation of insulin-degrading enzyme modulates mitochondrial amyloid β (Aβ) peptide catabolism and functionality
spellingShingle Transcriptional regulation of insulin-degrading enzyme modulates mitochondrial amyloid β (Aβ) peptide catabolism and functionality
Leal, Maria Celeste
Alzheimer disease
amyloid β peptide
insulin-degrading enzyme isoform
IDE
title_short Transcriptional regulation of insulin-degrading enzyme modulates mitochondrial amyloid β (Aβ) peptide catabolism and functionality
title_full Transcriptional regulation of insulin-degrading enzyme modulates mitochondrial amyloid β (Aβ) peptide catabolism and functionality
title_fullStr Transcriptional regulation of insulin-degrading enzyme modulates mitochondrial amyloid β (Aβ) peptide catabolism and functionality
title_full_unstemmed Transcriptional regulation of insulin-degrading enzyme modulates mitochondrial amyloid β (Aβ) peptide catabolism and functionality
title_sort Transcriptional regulation of insulin-degrading enzyme modulates mitochondrial amyloid β (Aβ) peptide catabolism and functionality
dc.creator.none.fl_str_mv Leal, Maria Celeste
Magnani, Natalia Daniela
Villordo, Sergio
Marino, Cristina Ester
Evelson, Pablo Andres
Castaño, Eduardo Miguel
Morelli, Laura
author Leal, Maria Celeste
author_facet Leal, Maria Celeste
Magnani, Natalia Daniela
Villordo, Sergio
Marino, Cristina Ester
Evelson, Pablo Andres
Castaño, Eduardo Miguel
Morelli, Laura
author_role author
author2 Magnani, Natalia Daniela
Villordo, Sergio
Marino, Cristina Ester
Evelson, Pablo Andres
Castaño, Eduardo Miguel
Morelli, Laura
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Alzheimer disease
amyloid β peptide
insulin-degrading enzyme isoform
IDE
topic Alzheimer disease
amyloid β peptide
insulin-degrading enzyme isoform
IDE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Studies of post-mortem brains from Alzheimer disease patients suggest that oxidative damage induced by mitochondrial amyloid β (mitAβ) accumulation is associated with mitochondrial dysfunction. However, the regulation of mitAβ metabolism is unknown. One of the proteases involved in mitAβ catabolism is the long insulin-degrading enzyme (IDE) isoform (IDE-Met(1)). However, the mechanisms of its expression are unknown, and its presence in brain is uncertain. We detected IDE-Met(1) in brain and showed that its expression is regulated by the mitochondrial biogenesis pathway (PGC-1α/NRF-1). A strong positive correlation between PGC-1α or NRF-1 and long IDE isoform transcripts was found in non-demented brains. This correlation was weaker in Alzheimer disease. In vitro inhibition of IDE increased mitAβ and impaired mitochondrial respiration. These changes were restored by inhibition of γ-secretase or promotion of mitochondrial biogenesis. Our results suggest that IDE-Met(1) links the mitochondrial biogenesis pathway with mitAβ levels and organelle functionality.
Fil: Leal, Maria Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Magnani, Natalia Daniela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Villordo, Sergio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Marino, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Evelson, Pablo Andres. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
Fil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Morelli, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
description Studies of post-mortem brains from Alzheimer disease patients suggest that oxidative damage induced by mitochondrial amyloid β (mitAβ) accumulation is associated with mitochondrial dysfunction. However, the regulation of mitAβ metabolism is unknown. One of the proteases involved in mitAβ catabolism is the long insulin-degrading enzyme (IDE) isoform (IDE-Met(1)). However, the mechanisms of its expression are unknown, and its presence in brain is uncertain. We detected IDE-Met(1) in brain and showed that its expression is regulated by the mitochondrial biogenesis pathway (PGC-1α/NRF-1). A strong positive correlation between PGC-1α or NRF-1 and long IDE isoform transcripts was found in non-demented brains. This correlation was weaker in Alzheimer disease. In vitro inhibition of IDE increased mitAβ and impaired mitochondrial respiration. These changes were restored by inhibition of γ-secretase or promotion of mitochondrial biogenesis. Our results suggest that IDE-Met(1) links the mitochondrial biogenesis pathway with mitAβ levels and organelle functionality.
publishDate 2013
dc.date.none.fl_str_mv 2013-05
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/11336/19716
Leal, Maria Celeste; Magnani, Natalia Daniela; Villordo, Sergio; Marino, Cristina Ester; Evelson, Pablo Andres; et al.; Transcriptional regulation of insulin-degrading enzyme modulates mitochondrial amyloid β (Aβ) peptide catabolism and functionality; American Society For Biochemistry And Molecular Biology; Journal Of Biological Chemistry; 288; 18; 5-2013; 12920-12931
0021-9258
1083-351X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/19716
identifier_str_mv Leal, Maria Celeste; Magnani, Natalia Daniela; Villordo, Sergio; Marino, Cristina Ester; Evelson, Pablo Andres; et al.; Transcriptional regulation of insulin-degrading enzyme modulates mitochondrial amyloid β (Aβ) peptide catabolism and functionality; American Society For Biochemistry And Molecular Biology; Journal Of Biological Chemistry; 288; 18; 5-2013; 12920-12931
0021-9258
1083-351X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/288/18/12920.long
info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M112.424820
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
dc.publisher.none.fl_str_mv American Society For Biochemistry And Molecular Biology
publisher.none.fl_str_mv American Society For Biochemistry And Molecular Biology
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
_version_ 1842269439853068288
score 13.21921

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