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PARP-1 Modulates Amyloid Beta Peptide-Induced Neuronal Damage
Amyloid beta peptide (Aβ) causes neurodegeneration by several mechanisms including oxidative stress, which is known to induce DNA damage with the consequent activation of poly (ADP-ribose) polymerase (PARP-1). To elucidate the role of PARP-1 in the neurodegenerative process, SH-SY5Y neuroblastoma ce...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782458/ https://www.ncbi.nlm.nih.gov/pubmed/24086258 http://dx.doi.org/10.1371/journal.pone.0072169 |
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author | Martire, Sara Fuso, Andrea Rotili, Dante Tempera, Italo Giordano, Cesare De Zottis, Ivana Muzi, Alessia Vernole, Patrizia Graziani, Grazia Lococo, Emanuela Faraldi, Martina Maras, Bruno Scarpa, Sigfrido Mosca, Luciana d'Erme, Maria |
author_facet | Martire, Sara Fuso, Andrea Rotili, Dante Tempera, Italo Giordano, Cesare De Zottis, Ivana Muzi, Alessia Vernole, Patrizia Graziani, Grazia Lococo, Emanuela Faraldi, Martina Maras, Bruno Scarpa, Sigfrido Mosca, Luciana d'Erme, Maria |
author_sort | Martire, Sara |
collection | PubMed |
description | Amyloid beta peptide (Aβ) causes neurodegeneration by several mechanisms including oxidative stress, which is known to induce DNA damage with the consequent activation of poly (ADP-ribose) polymerase (PARP-1). To elucidate the role of PARP-1 in the neurodegenerative process, SH-SY5Y neuroblastoma cells were treated with Aβ(25–35) fragment in the presence or absence of MC2050, a new PARP-1 inhibitor. Aβ(25–35) induces an enhancement of PARP activity which is prevented by cell pre-treatment with MC2050. These data were confirmed by measuring PARP-1 activity in CHO cells transfected with amylod precursor protein and in vivo in brains specimens of TgCRND8 transgenic mice overproducing the amyloid peptide. Following Aβ(25–35) exposure a significant increase in intracellular ROS was observed. These data were supported by the finding that Aβ(25–35) induces DNA damage which in turn activates PARP-1. Challenge with Aβ(25–35) is also able to activate NF-kB via PARP-1, as demonstrated by NF-kB impairment upon MC2050 treatment. Moreover, Aβ(25–35) via PARP-1 induces a significant increase in the p53 protein level and a parallel decrease in the anti-apoptotic Bcl-2 protein. These overall data support the hypothesis of PARP-1 involvment in cellular responses induced by Aβ and hence a possible rationale for the implication of PARP-1 in neurodegeneration is discussed. |
format | Online Article Text |
id | pubmed-3782458 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37824582013-10-01 PARP-1 Modulates Amyloid Beta Peptide-Induced Neuronal Damage Martire, Sara Fuso, Andrea Rotili, Dante Tempera, Italo Giordano, Cesare De Zottis, Ivana Muzi, Alessia Vernole, Patrizia Graziani, Grazia Lococo, Emanuela Faraldi, Martina Maras, Bruno Scarpa, Sigfrido Mosca, Luciana d'Erme, Maria PLoS One Research Article Amyloid beta peptide (Aβ) causes neurodegeneration by several mechanisms including oxidative stress, which is known to induce DNA damage with the consequent activation of poly (ADP-ribose) polymerase (PARP-1). To elucidate the role of PARP-1 in the neurodegenerative process, SH-SY5Y neuroblastoma cells were treated with Aβ(25–35) fragment in the presence or absence of MC2050, a new PARP-1 inhibitor. Aβ(25–35) induces an enhancement of PARP activity which is prevented by cell pre-treatment with MC2050. These data were confirmed by measuring PARP-1 activity in CHO cells transfected with amylod precursor protein and in vivo in brains specimens of TgCRND8 transgenic mice overproducing the amyloid peptide. Following Aβ(25–35) exposure a significant increase in intracellular ROS was observed. These data were supported by the finding that Aβ(25–35) induces DNA damage which in turn activates PARP-1. Challenge with Aβ(25–35) is also able to activate NF-kB via PARP-1, as demonstrated by NF-kB impairment upon MC2050 treatment. Moreover, Aβ(25–35) via PARP-1 induces a significant increase in the p53 protein level and a parallel decrease in the anti-apoptotic Bcl-2 protein. These overall data support the hypothesis of PARP-1 involvment in cellular responses induced by Aβ and hence a possible rationale for the implication of PARP-1 in neurodegeneration is discussed. Public Library of Science 2013-09-24 /pmc/articles/PMC3782458/ /pubmed/24086258 http://dx.doi.org/10.1371/journal.pone.0072169 Text en © 2013 Martire et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Martire, Sara Fuso, Andrea Rotili, Dante Tempera, Italo Giordano, Cesare De Zottis, Ivana Muzi, Alessia Vernole, Patrizia Graziani, Grazia Lococo, Emanuela Faraldi, Martina Maras, Bruno Scarpa, Sigfrido Mosca, Luciana d'Erme, Maria PARP-1 Modulates Amyloid Beta Peptide-Induced Neuronal Damage |
title | PARP-1 Modulates Amyloid Beta Peptide-Induced Neuronal Damage |
title_full | PARP-1 Modulates Amyloid Beta Peptide-Induced Neuronal Damage |
title_fullStr | PARP-1 Modulates Amyloid Beta Peptide-Induced Neuronal Damage |
title_full_unstemmed | PARP-1 Modulates Amyloid Beta Peptide-Induced Neuronal Damage |
title_short | PARP-1 Modulates Amyloid Beta Peptide-Induced Neuronal Damage |
title_sort | parp-1 modulates amyloid beta peptide-induced neuronal damage |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782458/ https://www.ncbi.nlm.nih.gov/pubmed/24086258 http://dx.doi.org/10.1371/journal.pone.0072169 |
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