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How well can morphology assess cell death modality? A proteomics study
While the focus of attempts to classify cell death programs has finally shifted in 2010s from microscopy-based morphological characteristics to biochemical assays, more recent discoveries have put the underlying assumptions of many such assays under severe stress, mostly because of the limited speci...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045961/ https://www.ncbi.nlm.nih.gov/pubmed/27752363 http://dx.doi.org/10.1038/cddiscovery.2016.68 |
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author | Chernobrovkin, Alexey L Zubarev, Roman A |
author_facet | Chernobrovkin, Alexey L Zubarev, Roman A |
author_sort | Chernobrovkin, Alexey L |
collection | PubMed |
description | While the focus of attempts to classify cell death programs has finally shifted in 2010s from microscopy-based morphological characteristics to biochemical assays, more recent discoveries have put the underlying assumptions of many such assays under severe stress, mostly because of the limited specificity of the assays. On the other hand, proteomics can quantitatively measure the abundances of thousands of proteins in a single experiment. Thus proteomics could develop a modern alternative to both semiquantitative morphology assessment as well as single-molecule biochemical assays. Here we tested this hypothesis by analyzing the proteomes of cells dying after been treated with various chemical agents. The most striking finding is that, for a multivariate model based on the proteome changes in three cells lines, the regulation patterns of the 200–500 most abundant proteins typically attributed to household type more accurately reflect that of the proteins directly interacting with the drug than any other protein subset grouped by common function or biological process, including cell death. This is in broad agreement with the 'rigid cell death mechanics' model where drug action mechanism and morphological changes caused by it are bijectively linked. This finding, if confirmed, will open way for a broad use of proteomics in death modality assessment. |
format | Online Article Text |
id | pubmed-5045961 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-50459612016-10-17 How well can morphology assess cell death modality? A proteomics study Chernobrovkin, Alexey L Zubarev, Roman A Cell Death Discov Article While the focus of attempts to classify cell death programs has finally shifted in 2010s from microscopy-based morphological characteristics to biochemical assays, more recent discoveries have put the underlying assumptions of many such assays under severe stress, mostly because of the limited specificity of the assays. On the other hand, proteomics can quantitatively measure the abundances of thousands of proteins in a single experiment. Thus proteomics could develop a modern alternative to both semiquantitative morphology assessment as well as single-molecule biochemical assays. Here we tested this hypothesis by analyzing the proteomes of cells dying after been treated with various chemical agents. The most striking finding is that, for a multivariate model based on the proteome changes in three cells lines, the regulation patterns of the 200–500 most abundant proteins typically attributed to household type more accurately reflect that of the proteins directly interacting with the drug than any other protein subset grouped by common function or biological process, including cell death. This is in broad agreement with the 'rigid cell death mechanics' model where drug action mechanism and morphological changes caused by it are bijectively linked. This finding, if confirmed, will open way for a broad use of proteomics in death modality assessment. Nature Publishing Group 2016-10-03 /pmc/articles/PMC5045961/ /pubmed/27752363 http://dx.doi.org/10.1038/cddiscovery.2016.68 Text en Copyright © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Chernobrovkin, Alexey L Zubarev, Roman A How well can morphology assess cell death modality? A proteomics study |
title | How well can morphology assess cell death modality? A proteomics study |
title_full | How well can morphology assess cell death modality? A proteomics study |
title_fullStr | How well can morphology assess cell death modality? A proteomics study |
title_full_unstemmed | How well can morphology assess cell death modality? A proteomics study |
title_short | How well can morphology assess cell death modality? A proteomics study |
title_sort | how well can morphology assess cell death modality? a proteomics study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045961/ https://www.ncbi.nlm.nih.gov/pubmed/27752363 http://dx.doi.org/10.1038/cddiscovery.2016.68 |
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