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

doi:10.1371/journal.pone.0163896

	Proteomic Analysis Implicates Dominant Alterations of RNA Metabolism and the Proteasome Pathway in the Cellular Response to Carbon-Ion Irradiation
	Wang, Yu 1; Guan, Hua 1; Xie, Da-Fei 1; Xie, Yi2 ; Liu, Xiao-Dan 1; Wang, Qi 1; Sui, Li 5; Song, Man 1,4; Zhang, Hong2 ; Zhou, Jianhua 3,6
刊名	PLOS ONE
	2016-10-06
卷号	11 页码:20
ISSN号	1932-6203
DOI	10.1371/journal.pone.0163896
英文摘要	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 C-12. 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/mu m, 313 proteins (8.2%) in cells irradiated at 2 Gy of carbon-ion radiation with 12.6 keV/mu m, and 243 proteins (6.4%) in cells irradiated at 2 Gy of carbon-ion radiation with 31.5 keV/mu m 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.
资助项目	National Natural Science Foundation of China[U1432248] ; iBioinfo Groups
WOS关键词	DOUBLE-STRAND BREAKS ; HUMAN LYMPHOBLASTOID-CELLS ; DOSE IONIZING-RADIATION ; DNA-DAMAGE RESPONSE ; BINDING PROTEIN HUR ; IDENTIFICATION ; RADIOTHERAPY ; REPAIR ; GENES ; RESISTANCE
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000385697600047
资助机构	National Natural Science Foundation of China ; iBioinfo Groups
内容类型	期刊论文
源URL	[http://119.78.100.186/handle/113462/43575]
专题	中国科学院近代物理研究所
通讯作者	Zhou, Jianhua; Zhou, Ping-Kun
作者单位	1.Beijing Inst Radiat Med, Dept Radiat Toxicol & Oncol, Beijing Key Lab Radiat Biol, Beijing, Peoples R China 2.Chinese Acad Sci, Inst Modern Phys, Dept Heavy Ion Radiat Med, Lanzhou 730000, Peoples R China 3.iBioinfo Grp, Lexington, MA 02421 USA 4.Soochow Univ, Sch Radiat Med & Protect, Jiangsu Higher Educ Inst, Collaborat Innovat Ctr Radiat Med, Suzhou, Peoples R China 5.China Inst Atom Energy, Beijing 102413, Peoples R China 6.Nantong Univ, Dept Neuroregenerat, Nantong, Peoples R China
推荐引用方式 GB/T 7714	Wang, Yu,Guan, Hua,Xie, Da-Fei,et al. Proteomic Analysis Implicates Dominant Alterations of RNA Metabolism and the Proteasome Pathway in the Cellular Response to Carbon-Ion Irradiation[J]. PLOS ONE,2016,11:20.
APA	Wang, Yu.,Guan, Hua.,Xie, Da-Fei.,Xie, Yi.,Liu, Xiao-Dan.,...&Zhou, Ping-Kun.(2016).Proteomic Analysis Implicates Dominant Alterations of RNA Metabolism and the Proteasome Pathway in the Cellular Response to Carbon-Ion Irradiation.PLOS ONE,11,20.
MLA	Wang, Yu,et al."Proteomic Analysis Implicates Dominant Alterations of RNA Metabolism and the Proteasome Pathway in the Cellular Response to Carbon-Ion Irradiation".PLOS ONE 11(2016):20.