Metabolic and Growth Rate Alterations in Lymphoblastic Cell Lines Discriminate between Down Syndrome and Alzheimer's Disease

Autores
Coskun, Pinar; Helguera, Pablo Rodolfo; Nemati, Zahra; Bohannan, Ryan C.; Thomas, Jean; Samuel, Schriner E.; Argueta, Jocelyn; Doran, Eric; Wallace, Douglas C.; Lott, Ira T.; Busciglio, Jorge
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Deficits in mitochondrial function and oxidative stress play pivotal roles in Down syndrome (DS) and Alzheimer's disease (AD) and these alterations in mitochondria occur systemically in both conditions. Objective: We hypothesized that peripheral cells of elder subjects with DS exhibit disease-specific and dementia-specific metabolic features. To test this, we performed a comprehensive analysis of energy metabolism in lymphoblastic-cell-lines (LCLs) derived from subjects belonging to four groups: DS-with-dementia (DSAD), DS-without-dementia (DS), sporadic AD, and age-matched controls. Methods: LCLs were studied under regular or minimal feeding regimes with galactose or glucose as primary carbohydrate sources. We assessed metabolism under glycolysis or oxidative phosphorylation by quantifying cell viability, oxidative stress, ATP levels, mitochondrial membrane potential (MMP), mitochondrial calcium uptake, and autophagy. DS and DSAD LCLs showed slower growth rates under minimal feeding. DS LCLs mainly dependent on mitochondrial respiration exhibited significantly slower growth and higher levels of oxidative stress compared to other groups. While ATP levels (under mitochondrial inhibitors) and mitochondrial calcium uptake were significantly reduced in DSAD and AD cells, MMP was decreased in DS, DSAD, and AD LCLs. Finally, DS LCLs showed markedly reduced levels of the autophagy marker LC3-II, underscoring the close association between metabolic dysfunction and impaired autophagy in DS. Conclusion: There are significant mitochondrial functional changes in LCLs derived from DS, DSAD, and AD patients. Several parameters analyzed were consistently different between DS, DSAD, and AD lines suggesting that metabolic indicators between LCL groups may be utilized as biomarkers of disease progression and/or treatment outcomes.
Fil: Coskun, Pinar. University of California at Irvine; Estados Unidos
Fil: Helguera, Pablo Rodolfo. University of California at Irvine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Nemati, Zahra. University of California at Irvine; Estados Unidos
Fil: Bohannan, Ryan C.. University of California at Irvine; Estados Unidos
Fil: Thomas, Jean. University of California at Irvine; Estados Unidos
Fil: Samuel, Schriner E.. University of California at Irvine; Estados Unidos
Fil: Argueta, Jocelyn. University of California at Irvine; Estados Unidos
Fil: Doran, Eric. University of California at Irvine; Estados Unidos
Fil: Wallace, Douglas C.. University of Pennsylvania; Estados Unidos
Fil: Lott, Ira T.. University of California at Irvine; Estados Unidos
Fil: Busciglio, Jorge. University of California at Irvine; Estados Unidos
Materia
Alzheimer'S Disease
Autophagy
Dementia
Down Syndrome
Growth Retardation
Lymphoblastoid Cell Lines
Metabolic Alterations
Mitochondrial Dysfunction
Oxidative Stress
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:11336/76545

id CONICETDig_75aaf6bd1129f5a089762699f72da19c
oai_identifier_str oai:ri.conicet.gov.ar:11336/76545
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Metabolic and Growth Rate Alterations in Lymphoblastic Cell Lines Discriminate between Down Syndrome and Alzheimer's DiseaseCoskun, PinarHelguera, Pablo RodolfoNemati, ZahraBohannan, Ryan C.Thomas, JeanSamuel, Schriner E.Argueta, JocelynDoran, EricWallace, Douglas C.Lott, Ira T.Busciglio, JorgeAlzheimer'S DiseaseAutophagyDementiaDown SyndromeGrowth RetardationLymphoblastoid Cell LinesMetabolic AlterationsMitochondrial DysfunctionOxidative Stresshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Deficits in mitochondrial function and oxidative stress play pivotal roles in Down syndrome (DS) and Alzheimer's disease (AD) and these alterations in mitochondria occur systemically in both conditions. Objective: We hypothesized that peripheral cells of elder subjects with DS exhibit disease-specific and dementia-specific metabolic features. To test this, we performed a comprehensive analysis of energy metabolism in lymphoblastic-cell-lines (LCLs) derived from subjects belonging to four groups: DS-with-dementia (DSAD), DS-without-dementia (DS), sporadic AD, and age-matched controls. Methods: LCLs were studied under regular or minimal feeding regimes with galactose or glucose as primary carbohydrate sources. We assessed metabolism under glycolysis or oxidative phosphorylation by quantifying cell viability, oxidative stress, ATP levels, mitochondrial membrane potential (MMP), mitochondrial calcium uptake, and autophagy. DS and DSAD LCLs showed slower growth rates under minimal feeding. DS LCLs mainly dependent on mitochondrial respiration exhibited significantly slower growth and higher levels of oxidative stress compared to other groups. While ATP levels (under mitochondrial inhibitors) and mitochondrial calcium uptake were significantly reduced in DSAD and AD cells, MMP was decreased in DS, DSAD, and AD LCLs. Finally, DS LCLs showed markedly reduced levels of the autophagy marker LC3-II, underscoring the close association between metabolic dysfunction and impaired autophagy in DS. Conclusion: There are significant mitochondrial functional changes in LCLs derived from DS, DSAD, and AD patients. Several parameters analyzed were consistently different between DS, DSAD, and AD lines suggesting that metabolic indicators between LCL groups may be utilized as biomarkers of disease progression and/or treatment outcomes.Fil: Coskun, Pinar. University of California at Irvine; Estados UnidosFil: Helguera, Pablo Rodolfo. University of California at Irvine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Nemati, Zahra. University of California at Irvine; Estados UnidosFil: Bohannan, Ryan C.. University of California at Irvine; Estados UnidosFil: Thomas, Jean. University of California at Irvine; Estados UnidosFil: Samuel, Schriner E.. University of California at Irvine; Estados UnidosFil: Argueta, Jocelyn. University of California at Irvine; Estados UnidosFil: Doran, Eric. University of California at Irvine; Estados UnidosFil: Wallace, Douglas C.. University of Pennsylvania; Estados UnidosFil: Lott, Ira T.. University of California at Irvine; Estados UnidosFil: Busciglio, Jorge. University of California at Irvine; Estados UnidosIOS Press2016-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/76545Coskun, Pinar; Helguera, Pablo Rodolfo; Nemati, Zahra; Bohannan, Ryan C.; Thomas, Jean; et al.; Metabolic and Growth Rate Alterations in Lymphoblastic Cell Lines Discriminate between Down Syndrome and Alzheimer's Disease; IOS Press; Journal of Alzheimer's Disease; 55; 2; 8-2016; 737-7481387-2877CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3233/JAD-160278info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/27802222info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:37:57Zoai:ri.conicet.gov.ar:11336/76545instacron: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 09:37:57.553CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Metabolic and Growth Rate Alterations in Lymphoblastic Cell Lines Discriminate between Down Syndrome and Alzheimer's Disease
title Metabolic and Growth Rate Alterations in Lymphoblastic Cell Lines Discriminate between Down Syndrome and Alzheimer's Disease
spellingShingle Metabolic and Growth Rate Alterations in Lymphoblastic Cell Lines Discriminate between Down Syndrome and Alzheimer's Disease
Coskun, Pinar
Alzheimer'S Disease
Autophagy
Dementia
Down Syndrome
Growth Retardation
Lymphoblastoid Cell Lines
Metabolic Alterations
Mitochondrial Dysfunction
Oxidative Stress
title_short Metabolic and Growth Rate Alterations in Lymphoblastic Cell Lines Discriminate between Down Syndrome and Alzheimer's Disease
title_full Metabolic and Growth Rate Alterations in Lymphoblastic Cell Lines Discriminate between Down Syndrome and Alzheimer's Disease
title_fullStr Metabolic and Growth Rate Alterations in Lymphoblastic Cell Lines Discriminate between Down Syndrome and Alzheimer's Disease
title_full_unstemmed Metabolic and Growth Rate Alterations in Lymphoblastic Cell Lines Discriminate between Down Syndrome and Alzheimer's Disease
title_sort Metabolic and Growth Rate Alterations in Lymphoblastic Cell Lines Discriminate between Down Syndrome and Alzheimer's Disease
dc.creator.none.fl_str_mv Coskun, Pinar
Helguera, Pablo Rodolfo
Nemati, Zahra
Bohannan, Ryan C.
Thomas, Jean
Samuel, Schriner E.
Argueta, Jocelyn
Doran, Eric
Wallace, Douglas C.
Lott, Ira T.
Busciglio, Jorge
author Coskun, Pinar
author_facet Coskun, Pinar
Helguera, Pablo Rodolfo
Nemati, Zahra
Bohannan, Ryan C.
Thomas, Jean
Samuel, Schriner E.
Argueta, Jocelyn
Doran, Eric
Wallace, Douglas C.
Lott, Ira T.
Busciglio, Jorge
author_role author
author2 Helguera, Pablo Rodolfo
Nemati, Zahra
Bohannan, Ryan C.
Thomas, Jean
Samuel, Schriner E.
Argueta, Jocelyn
Doran, Eric
Wallace, Douglas C.
Lott, Ira T.
Busciglio, Jorge
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Alzheimer'S Disease
Autophagy
Dementia
Down Syndrome
Growth Retardation
Lymphoblastoid Cell Lines
Metabolic Alterations
Mitochondrial Dysfunction
Oxidative Stress
topic Alzheimer'S Disease
Autophagy
Dementia
Down Syndrome
Growth Retardation
Lymphoblastoid Cell Lines
Metabolic Alterations
Mitochondrial Dysfunction
Oxidative Stress
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Deficits in mitochondrial function and oxidative stress play pivotal roles in Down syndrome (DS) and Alzheimer's disease (AD) and these alterations in mitochondria occur systemically in both conditions. Objective: We hypothesized that peripheral cells of elder subjects with DS exhibit disease-specific and dementia-specific metabolic features. To test this, we performed a comprehensive analysis of energy metabolism in lymphoblastic-cell-lines (LCLs) derived from subjects belonging to four groups: DS-with-dementia (DSAD), DS-without-dementia (DS), sporadic AD, and age-matched controls. Methods: LCLs were studied under regular or minimal feeding regimes with galactose or glucose as primary carbohydrate sources. We assessed metabolism under glycolysis or oxidative phosphorylation by quantifying cell viability, oxidative stress, ATP levels, mitochondrial membrane potential (MMP), mitochondrial calcium uptake, and autophagy. DS and DSAD LCLs showed slower growth rates under minimal feeding. DS LCLs mainly dependent on mitochondrial respiration exhibited significantly slower growth and higher levels of oxidative stress compared to other groups. While ATP levels (under mitochondrial inhibitors) and mitochondrial calcium uptake were significantly reduced in DSAD and AD cells, MMP was decreased in DS, DSAD, and AD LCLs. Finally, DS LCLs showed markedly reduced levels of the autophagy marker LC3-II, underscoring the close association between metabolic dysfunction and impaired autophagy in DS. Conclusion: There are significant mitochondrial functional changes in LCLs derived from DS, DSAD, and AD patients. Several parameters analyzed were consistently different between DS, DSAD, and AD lines suggesting that metabolic indicators between LCL groups may be utilized as biomarkers of disease progression and/or treatment outcomes.
Fil: Coskun, Pinar. University of California at Irvine; Estados Unidos
Fil: Helguera, Pablo Rodolfo. University of California at Irvine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
Fil: Nemati, Zahra. University of California at Irvine; Estados Unidos
Fil: Bohannan, Ryan C.. University of California at Irvine; Estados Unidos
Fil: Thomas, Jean. University of California at Irvine; Estados Unidos
Fil: Samuel, Schriner E.. University of California at Irvine; Estados Unidos
Fil: Argueta, Jocelyn. University of California at Irvine; Estados Unidos
Fil: Doran, Eric. University of California at Irvine; Estados Unidos
Fil: Wallace, Douglas C.. University of Pennsylvania; Estados Unidos
Fil: Lott, Ira T.. University of California at Irvine; Estados Unidos
Fil: Busciglio, Jorge. University of California at Irvine; Estados Unidos
description Deficits in mitochondrial function and oxidative stress play pivotal roles in Down syndrome (DS) and Alzheimer's disease (AD) and these alterations in mitochondria occur systemically in both conditions. Objective: We hypothesized that peripheral cells of elder subjects with DS exhibit disease-specific and dementia-specific metabolic features. To test this, we performed a comprehensive analysis of energy metabolism in lymphoblastic-cell-lines (LCLs) derived from subjects belonging to four groups: DS-with-dementia (DSAD), DS-without-dementia (DS), sporadic AD, and age-matched controls. Methods: LCLs were studied under regular or minimal feeding regimes with galactose or glucose as primary carbohydrate sources. We assessed metabolism under glycolysis or oxidative phosphorylation by quantifying cell viability, oxidative stress, ATP levels, mitochondrial membrane potential (MMP), mitochondrial calcium uptake, and autophagy. DS and DSAD LCLs showed slower growth rates under minimal feeding. DS LCLs mainly dependent on mitochondrial respiration exhibited significantly slower growth and higher levels of oxidative stress compared to other groups. While ATP levels (under mitochondrial inhibitors) and mitochondrial calcium uptake were significantly reduced in DSAD and AD cells, MMP was decreased in DS, DSAD, and AD LCLs. Finally, DS LCLs showed markedly reduced levels of the autophagy marker LC3-II, underscoring the close association between metabolic dysfunction and impaired autophagy in DS. Conclusion: There are significant mitochondrial functional changes in LCLs derived from DS, DSAD, and AD patients. Several parameters analyzed were consistently different between DS, DSAD, and AD lines suggesting that metabolic indicators between LCL groups may be utilized as biomarkers of disease progression and/or treatment outcomes.
publishDate 2016
dc.date.none.fl_str_mv 2016-08
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/11336/76545
Coskun, Pinar; Helguera, Pablo Rodolfo; Nemati, Zahra; Bohannan, Ryan C.; Thomas, Jean; et al.; Metabolic and Growth Rate Alterations in Lymphoblastic Cell Lines Discriminate between Down Syndrome and Alzheimer's Disease; IOS Press; Journal of Alzheimer's Disease; 55; 2; 8-2016; 737-748
1387-2877
CONICET Digital
CONICET
url http://hdl.handle.net/11336/76545
identifier_str_mv Coskun, Pinar; Helguera, Pablo Rodolfo; Nemati, Zahra; Bohannan, Ryan C.; Thomas, Jean; et al.; Metabolic and Growth Rate Alterations in Lymphoblastic Cell Lines Discriminate between Down Syndrome and Alzheimer's Disease; IOS Press; Journal of Alzheimer's Disease; 55; 2; 8-2016; 737-748
1387-2877
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3233/JAD-160278
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/27802222
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 IOS Press
publisher.none.fl_str_mv IOS Press
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_ 1844613198340161536
score 13.070432