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Cytotoxic effects of G(M1) ganglioside and amyloid β-peptide on mouse embryonic neural stem cells
AD (Alzheimer’s disease) is a neurodegenerative disease and the most common form of dementia. One of the pathological hallmarks of AD is the aggregation of extracellular Aβs (amyloid β-peptides) in senile plaques in the brain. The process could be initiated by seeding provided by an interaction betw...
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Formato: | Texto |
Lenguaje: | English |
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American Society for Neurochemistry
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2838405/ https://www.ncbi.nlm.nih.gov/pubmed/20305711 http://dx.doi.org/10.1042/AN20090063 |
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author | Yanagisawa, Makoto Ariga, Toshio Yu, Robert K |
author_facet | Yanagisawa, Makoto Ariga, Toshio Yu, Robert K |
author_sort | Yanagisawa, Makoto |
collection | PubMed |
description | AD (Alzheimer’s disease) is a neurodegenerative disease and the most common form of dementia. One of the pathological hallmarks of AD is the aggregation of extracellular Aβs (amyloid β-peptides) in senile plaques in the brain. The process could be initiated by seeding provided by an interaction between G(M1) ganglioside and Aβs. Several reports have documented the bifunctional roles of Aβs in NSCs (neural stem cells), but the precise effects of G(M1) and Aβ on NSCs have not yet been clarified. We evaluated the effect of G(M1) and Aβ-(1–40) on mouse NECs (neuroepithelial cells), which are known to be rich in NSCs. No change of cell number was detected in NECs cultured in the presence of either G(M1) or Aβ-(1–40). On the contrary, a decreased number of NECs were cultured in the presence of a combination of G(M1) and Aβ-(1–40). The exogenously added G(M1) and Aβ-(1–40) were confirmed to incorporate into NECs. The Ras–MAPK (mitogen-activated protein kinase) pathway, important for cell proliferation, was intact in NECs simultaneously treated with G(M1) and Aβ-(1–40), but caspase 3 was activated. NECs treated with G(M1) and Aβ-(1–40) were positive in the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay, an indicator of cell death. It was found that G(M1) and Aβ-(1–40) interacted in the presence of cholesterol and sphingomyelin, components of cell surface microdomains. The cytotoxic effect was found also in NSCs prepared via neurospheres. These results indicate that Aβ-(1–40) and G(M1) co-operatively exert a cytotoxic effect on NSCs, likely via incorporation into NEC membranes, where they form a complex for the activation of cell death signalling. |
format | Text |
id | pubmed-2838405 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | American Society for Neurochemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-28384052010-03-19 Cytotoxic effects of G(M1) ganglioside and amyloid β-peptide on mouse embryonic neural stem cells Yanagisawa, Makoto Ariga, Toshio Yu, Robert K ASN Neuro Research Article AD (Alzheimer’s disease) is a neurodegenerative disease and the most common form of dementia. One of the pathological hallmarks of AD is the aggregation of extracellular Aβs (amyloid β-peptides) in senile plaques in the brain. The process could be initiated by seeding provided by an interaction between G(M1) ganglioside and Aβs. Several reports have documented the bifunctional roles of Aβs in NSCs (neural stem cells), but the precise effects of G(M1) and Aβ on NSCs have not yet been clarified. We evaluated the effect of G(M1) and Aβ-(1–40) on mouse NECs (neuroepithelial cells), which are known to be rich in NSCs. No change of cell number was detected in NECs cultured in the presence of either G(M1) or Aβ-(1–40). On the contrary, a decreased number of NECs were cultured in the presence of a combination of G(M1) and Aβ-(1–40). The exogenously added G(M1) and Aβ-(1–40) were confirmed to incorporate into NECs. The Ras–MAPK (mitogen-activated protein kinase) pathway, important for cell proliferation, was intact in NECs simultaneously treated with G(M1) and Aβ-(1–40), but caspase 3 was activated. NECs treated with G(M1) and Aβ-(1–40) were positive in the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay, an indicator of cell death. It was found that G(M1) and Aβ-(1–40) interacted in the presence of cholesterol and sphingomyelin, components of cell surface microdomains. The cytotoxic effect was found also in NSCs prepared via neurospheres. These results indicate that Aβ-(1–40) and G(M1) co-operatively exert a cytotoxic effect on NSCs, likely via incorporation into NEC membranes, where they form a complex for the activation of cell death signalling. American Society for Neurochemistry 2010-03-15 /pmc/articles/PMC2838405/ /pubmed/20305711 http://dx.doi.org/10.1042/AN20090063 Text en © 2010 The Author(s). http://creativecommons.org/licenses/by-nc/2.5/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Licence (http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Yanagisawa, Makoto Ariga, Toshio Yu, Robert K Cytotoxic effects of G(M1) ganglioside and amyloid β-peptide on mouse embryonic neural stem cells |
title | Cytotoxic effects of G(M1) ganglioside and amyloid β-peptide on mouse embryonic neural stem cells |
title_full | Cytotoxic effects of G(M1) ganglioside and amyloid β-peptide on mouse embryonic neural stem cells |
title_fullStr | Cytotoxic effects of G(M1) ganglioside and amyloid β-peptide on mouse embryonic neural stem cells |
title_full_unstemmed | Cytotoxic effects of G(M1) ganglioside and amyloid β-peptide on mouse embryonic neural stem cells |
title_short | Cytotoxic effects of G(M1) ganglioside and amyloid β-peptide on mouse embryonic neural stem cells |
title_sort | cytotoxic effects of g(m1) ganglioside and amyloid β-peptide on mouse embryonic neural stem cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2838405/ https://www.ncbi.nlm.nih.gov/pubmed/20305711 http://dx.doi.org/10.1042/AN20090063 |
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