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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/76545
Ver los metadatos del registro completo
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 |