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Elevated levels of pro-apoptotic p53 and its oxidative modification by the lipid peroxidation product, HNE,in brain from subjects with amnestic mild cognitive impairment and Alzheimer's disease
Oxidative stress has been implicated in the pathogenesis of Alzheimer's disease (AD). Both AD and arguably its earlier form, mild cognitive impairment (MCI), have elevated membrane oxidative damage in brain. The tumor suppressor and transcription factor p53 plays a pivotal function in neuronal...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401131/ https://www.ncbi.nlm.nih.gov/pubmed/18494939 http://dx.doi.org/10.1111/j.1582-4934.2008.00163.x |
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author | Cenini, Giovanna Sultana, Rukhsana Memo, Maurizio Butterfield, D Allan |
author_facet | Cenini, Giovanna Sultana, Rukhsana Memo, Maurizio Butterfield, D Allan |
author_sort | Cenini, Giovanna |
collection | PubMed |
description | Oxidative stress has been implicated in the pathogenesis of Alzheimer's disease (AD). Both AD and arguably its earlier form, mild cognitive impairment (MCI), have elevated membrane oxidative damage in brain. The tumor suppressor and transcription factor p53 plays a pivotal function in neuronal apoptosis triggered by oxidative stress. Apoptosis contributes to neuronal death in many neurological disorders, including AD. In this study, we investigated p53 expression in a specific region of the cerebral cortex, namely the inferior parietal lobule (IPL), in MCI and AD brain, to test the hypothesis that alterations of this pro-apoptotic protein may be involved in neuronal death in the progression of AD. By immunoprecipitation assay, we also investigated whether 4-hydroxy-2-transnonenal (HNE), an aldehydic product of lipid peroxidation, was bound in excess to p53 in IPL from subjects with MCI and AD compared to control. Overall, the data provide evidence that p53 is involved in the neuronal death in both MCI and AD, suggesting that the observed alterations are early events in the progression of AD. In addition, HNE may be a novel non-protein mediator of oxidative stress-induced neuronal apoptosis. |
format | Online Article Text |
id | pubmed-4401131 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-44011312015-04-27 Elevated levels of pro-apoptotic p53 and its oxidative modification by the lipid peroxidation product, HNE,in brain from subjects with amnestic mild cognitive impairment and Alzheimer's disease Cenini, Giovanna Sultana, Rukhsana Memo, Maurizio Butterfield, D Allan J Cell Mol Med Articles Oxidative stress has been implicated in the pathogenesis of Alzheimer's disease (AD). Both AD and arguably its earlier form, mild cognitive impairment (MCI), have elevated membrane oxidative damage in brain. The tumor suppressor and transcription factor p53 plays a pivotal function in neuronal apoptosis triggered by oxidative stress. Apoptosis contributes to neuronal death in many neurological disorders, including AD. In this study, we investigated p53 expression in a specific region of the cerebral cortex, namely the inferior parietal lobule (IPL), in MCI and AD brain, to test the hypothesis that alterations of this pro-apoptotic protein may be involved in neuronal death in the progression of AD. By immunoprecipitation assay, we also investigated whether 4-hydroxy-2-transnonenal (HNE), an aldehydic product of lipid peroxidation, was bound in excess to p53 in IPL from subjects with MCI and AD compared to control. Overall, the data provide evidence that p53 is involved in the neuronal death in both MCI and AD, suggesting that the observed alterations are early events in the progression of AD. In addition, HNE may be a novel non-protein mediator of oxidative stress-induced neuronal apoptosis. Blackwell Publishing Ltd 2008-06 2008-05-21 /pmc/articles/PMC4401131/ /pubmed/18494939 http://dx.doi.org/10.1111/j.1582-4934.2008.00163.x Text en © 2008 The Authors Journal compilation © 2008 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd |
spellingShingle | Articles Cenini, Giovanna Sultana, Rukhsana Memo, Maurizio Butterfield, D Allan Elevated levels of pro-apoptotic p53 and its oxidative modification by the lipid peroxidation product, HNE,in brain from subjects with amnestic mild cognitive impairment and Alzheimer's disease |
title | Elevated levels of pro-apoptotic p53 and its oxidative modification by the lipid peroxidation product, HNE,in brain from subjects with amnestic mild cognitive impairment and Alzheimer's disease |
title_full | Elevated levels of pro-apoptotic p53 and its oxidative modification by the lipid peroxidation product, HNE,in brain from subjects with amnestic mild cognitive impairment and Alzheimer's disease |
title_fullStr | Elevated levels of pro-apoptotic p53 and its oxidative modification by the lipid peroxidation product, HNE,in brain from subjects with amnestic mild cognitive impairment and Alzheimer's disease |
title_full_unstemmed | Elevated levels of pro-apoptotic p53 and its oxidative modification by the lipid peroxidation product, HNE,in brain from subjects with amnestic mild cognitive impairment and Alzheimer's disease |
title_short | Elevated levels of pro-apoptotic p53 and its oxidative modification by the lipid peroxidation product, HNE,in brain from subjects with amnestic mild cognitive impairment and Alzheimer's disease |
title_sort | elevated levels of pro-apoptotic p53 and its oxidative modification by the lipid peroxidation product, hne,in brain from subjects with amnestic mild cognitive impairment and alzheimer's disease |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4401131/ https://www.ncbi.nlm.nih.gov/pubmed/18494939 http://dx.doi.org/10.1111/j.1582-4934.2008.00163.x |
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