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Proteomic Analysis Implicates Dominant Alterations of RNA Metabolism and the Proteasome Pathway in the Cellular Response to Carbon-Ion Irradiation

Radiotherapy with heavy ions is considered advantageous compared to irradiation with photons due to the characteristics of the Braggs peak and the high linear energy transfer (LET) value. To understand the mechanisms of cellular responses to different LET values and dosages of heavy ion radiation, w...

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Autores principales: Wang, Yu, Guan, Hua, Xie, Da-Fei, Xie, Yi, Liu, Xiao-Dan, Wang, Qi, Sui, Li, Song, Man, Zhang, Hong, Zhou, Jianhua, Zhou, Ping-Kun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053480/
https://www.ncbi.nlm.nih.gov/pubmed/27711237
http://dx.doi.org/10.1371/journal.pone.0163896
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author Wang, Yu
Guan, Hua
Xie, Da-Fei
Xie, Yi
Liu, Xiao-Dan
Wang, Qi
Sui, Li
Song, Man
Zhang, Hong
Zhou, Jianhua
Zhou, Ping-Kun
author_facet Wang, Yu
Guan, Hua
Xie, Da-Fei
Xie, Yi
Liu, Xiao-Dan
Wang, Qi
Sui, Li
Song, Man
Zhang, Hong
Zhou, Jianhua
Zhou, Ping-Kun
author_sort Wang, Yu
collection PubMed
description Radiotherapy with heavy ions is considered advantageous compared to irradiation with photons due to the characteristics of the Braggs peak and the high linear energy transfer (LET) value. To understand the mechanisms of cellular responses to different LET values and dosages of heavy ion radiation, we analyzed the proteomic profiles of mouse embryo fibroblast MEF cells exposed to two doses from different LET values of heavy ion (12)C. Total proteins were extracted from these cells and examined by Q Exactive with Liquid Chromatography (LC)—Electrospray Ionization (ESI) Tandem MS (MS/MS). Using bioinformatics approaches, differentially expressed proteins with 1.5 or 2.0-fold changes between different dosages of exposure were compared. With the higher the dosage and/or LET of ion irradiation, the worse response the cells were in terms of protein expression. For instance, compared to the control (0 Gy), 771 (20.2%) proteins in cells irradiated at 0.2 Gy of carbon-ion radiation with 12.6 keV/μm, 313 proteins (8.2%) in cells irradiated at 2 Gy of carbon-ion radiation with 12.6 keV/μm, and 243 proteins (6.4%) in cells irradiated at 2 Gy of carbon-ion radiation with 31.5 keV/μm exhibited changes of 1.5-fold or greater. Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Munich Information Center for Protein Sequences (MIPS) analysis, and BioCarta analysis all indicated that RNA metabolic processes (RNA splicing, destabilization and deadenylation) and proteasome pathways may play key roles in the cellular response to heavy-ion irradiation. Proteasome pathways ranked highest among all biological processes associated with heavy carbon-ion irradiation. In addition, network analysis revealed that cellular pathways involving proteins such as Col1a1 and Fn1 continued to respond to high dosages of heavy-ion irradiation, suggesting that these pathways still protect cells against damage. However, pathways such as those involving Ikbkg1 responded better at lower dosages than at higher dosages, implying that cell damage would occur when the networks involving these proteins stop responding. Our investigation provides valuable proteomic information for elucidating the mechanism of biological effects induced by carbon ions in general.
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spelling pubmed-50534802016-10-27 Proteomic Analysis Implicates Dominant Alterations of RNA Metabolism and the Proteasome Pathway in the Cellular Response to Carbon-Ion Irradiation Wang, Yu Guan, Hua Xie, Da-Fei Xie, Yi Liu, Xiao-Dan Wang, Qi Sui, Li Song, Man Zhang, Hong Zhou, Jianhua Zhou, Ping-Kun PLoS One Research Article Radiotherapy with heavy ions is considered advantageous compared to irradiation with photons due to the characteristics of the Braggs peak and the high linear energy transfer (LET) value. To understand the mechanisms of cellular responses to different LET values and dosages of heavy ion radiation, we analyzed the proteomic profiles of mouse embryo fibroblast MEF cells exposed to two doses from different LET values of heavy ion (12)C. Total proteins were extracted from these cells and examined by Q Exactive with Liquid Chromatography (LC)—Electrospray Ionization (ESI) Tandem MS (MS/MS). Using bioinformatics approaches, differentially expressed proteins with 1.5 or 2.0-fold changes between different dosages of exposure were compared. With the higher the dosage and/or LET of ion irradiation, the worse response the cells were in terms of protein expression. For instance, compared to the control (0 Gy), 771 (20.2%) proteins in cells irradiated at 0.2 Gy of carbon-ion radiation with 12.6 keV/μm, 313 proteins (8.2%) in cells irradiated at 2 Gy of carbon-ion radiation with 12.6 keV/μm, and 243 proteins (6.4%) in cells irradiated at 2 Gy of carbon-ion radiation with 31.5 keV/μm exhibited changes of 1.5-fold or greater. Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Munich Information Center for Protein Sequences (MIPS) analysis, and BioCarta analysis all indicated that RNA metabolic processes (RNA splicing, destabilization and deadenylation) and proteasome pathways may play key roles in the cellular response to heavy-ion irradiation. Proteasome pathways ranked highest among all biological processes associated with heavy carbon-ion irradiation. In addition, network analysis revealed that cellular pathways involving proteins such as Col1a1 and Fn1 continued to respond to high dosages of heavy-ion irradiation, suggesting that these pathways still protect cells against damage. However, pathways such as those involving Ikbkg1 responded better at lower dosages than at higher dosages, implying that cell damage would occur when the networks involving these proteins stop responding. Our investigation provides valuable proteomic information for elucidating the mechanism of biological effects induced by carbon ions in general. Public Library of Science 2016-10-06 /pmc/articles/PMC5053480/ /pubmed/27711237 http://dx.doi.org/10.1371/journal.pone.0163896 Text en © 2016 Wang 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Wang, Yu
Guan, Hua
Xie, Da-Fei
Xie, Yi
Liu, Xiao-Dan
Wang, Qi
Sui, Li
Song, Man
Zhang, Hong
Zhou, Jianhua
Zhou, Ping-Kun
Proteomic Analysis Implicates Dominant Alterations of RNA Metabolism and the Proteasome Pathway in the Cellular Response to Carbon-Ion Irradiation
title Proteomic Analysis Implicates Dominant Alterations of RNA Metabolism and the Proteasome Pathway in the Cellular Response to Carbon-Ion Irradiation
title_full Proteomic Analysis Implicates Dominant Alterations of RNA Metabolism and the Proteasome Pathway in the Cellular Response to Carbon-Ion Irradiation
title_fullStr Proteomic Analysis Implicates Dominant Alterations of RNA Metabolism and the Proteasome Pathway in the Cellular Response to Carbon-Ion Irradiation
title_full_unstemmed Proteomic Analysis Implicates Dominant Alterations of RNA Metabolism and the Proteasome Pathway in the Cellular Response to Carbon-Ion Irradiation
title_short Proteomic Analysis Implicates Dominant Alterations of RNA Metabolism and the Proteasome Pathway in the Cellular Response to Carbon-Ion Irradiation
title_sort proteomic analysis implicates dominant alterations of rna metabolism and the proteasome pathway in the cellular response to carbon-ion irradiation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053480/
https://www.ncbi.nlm.nih.gov/pubmed/27711237
http://dx.doi.org/10.1371/journal.pone.0163896
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