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Heavy ion radiation-induced DNA damage mediates apoptosis via the Rp127a-Rp15-MDM2-p53/E2F1 signaling pathway in mouse spermatogonia

文献类型：期刊论文

作者Li, Hongyan1,2,3,4; Zhang, Hong1,2,3,4; Huang, Guomin1,2,3,4; Dou, Zhihui1,2,3,4; Xie, Yi1,2,3,4; Si, Jing1,2,3,4; Di, Cuixia1,2,3,4
刊名ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
出版日期2020-09-15
卷号201页码:12
ISSN号0147-6513
关键词Ionizing radiation Reproductive toxicology Ribosomal stress MDM2-p53 loop Apoptosis
DOI10.1016/j.ecoenv.2020.110831
通讯作者Zhang, Hong(zhangh@impcas.ac.cn)
英文摘要The risk of exposure to ionizing radiation (IR) environments has increased with the development of nuclear technology. IR exposure induces excessive apoptosis of the spermatogonia, which leads to male infertility. Spermatogonia apoptosis may be involved in ribosomal stress triggered by DNA damage following exposure to IR because ribosomal proteins (RPs) directly interact with mouse double minute 2 homolog (MDM2) to induce apoptosis. This study aimed to use comparative proteomics and transcriptomics approach to screen the differential RPs and ribosomal mRNAs in mouse testes following high linear energy transfer (LET) carbon ion radiation (CIR). The expression of ribosomal large subunit protein 27a (Rp127a) decreased at both protein and mRNA levels in the spermatogonia in vivo. After 6 h of CIR, the immunofluorescence signal of 8-oxo-dG and phosphorylated ataxia-telangiectasia-mutated protein (ATM)/histone H2Ax increased, but that of Rp127a decreased in the spermatogonia of p53 wild-type and knockout mouse testes. Moreover, the nucleolin was scattered throughout the nucleoplasm after CIR. These results suggested that CIR-induced DNA damage might trigger ribosomal stress, and the reduction in the expression of Rp127a was associated with DNA damage in the spermatogonia. Similarly, in vitro, the immunofluorescence signal of 8-oxo-dG increased in the GC-1 cells after CIR. Moreover, the expression of Rp127a was regulated by DNA damage because the co-transfection of ATM and Rp127a or inhibition of ATM-treated CIR could restore the expression of Rp127a. Furthermore, the reduction in the expression of Rp127a led to weakened binding of E2F transcription factor 1 (E2F1) and p53 to MDM2, causing p53 activation and E2F1 degradation in p53 wild-type and knockdown GC-1 cells. This study proposed that heavy ion radiation-induced DNA damage mediated spermatogonia apoptosis via the Rp127a-Rp15-MDM2-p53/E2F1 signaling pathway. The results provided the underlying molecular mechanisms of spermatogonia apoptosis following exposure to high LET radiation.
WOS关键词TUMOR-SUPPRESSOR P53 ; RIBOSOMAL-PROTEINS ; STRESS ; IRRADIATION ; GENE ; BIOGENESIS ; ACTIVATION ; EXPRESSION ; EXPOSURE ; TARGET
资助项目National Key R&D Program of China[2018YFE0205100] ; National Natural Science Foundation of China[11875061] ; National Natural Science Foundation of China[11505244] ; Western Talent Program of the Chinese Academy of Sciences[Y560020XB0] ; Key Program of the National Natural Science Foundation of China[U1632270]
WOS研究方向Environmental Sciences & Ecology ; Toxicology
语种英语
出版者ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号WOS:000546898000059
资助机构National Key R&D Program of China ; National Natural Science Foundation of China ; Western Talent Program of the Chinese Academy of Sciences ; Key Program of the National Natural Science Foundation of China
源URL[http://119.78.100.186/handle/113462/140323]  
专题中国科学院近代物理研究所
通讯作者Zhang, Hong
作者单位1.Univ Chinese Acad Sci, Sch Nucl Sci & Technol, Beijing 100039, Peoples R China
2.Chinese Acad Sci, Inst Modern Phys, Dept Med Phys, Lanzhou 730000, Peoples R China
3.Chinese Acad Sci, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou 730000, Peoples R China
4.Key Lab Basic Res Heavy Ion Radiat Applicat Med, Lanzhou 730000, Peoples R China
推荐引用方式
GB/T 7714		 Li, Hongyan,Zhang, Hong,Huang, Guomin,et al. Heavy ion radiation-induced DNA damage mediates apoptosis via the Rp127a-Rp15-MDM2-p53/E2F1 signaling pathway in mouse spermatogonia[J]. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY,2020,201:12.
APA Li, Hongyan.,Zhang, Hong.,Huang, Guomin.,Dou, Zhihui.,Xie, Yi.,...&Di, Cuixia.(2020).Heavy ion radiation-induced DNA damage mediates apoptosis via the Rp127a-Rp15-MDM2-p53/E2F1 signaling pathway in mouse spermatogonia.ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY,201,12.
MLA Li, Hongyan,et al."Heavy ion radiation-induced DNA damage mediates apoptosis via the Rp127a-Rp15-MDM2-p53/E2F1 signaling pathway in mouse spermatogonia".ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 201(2020):12.

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来源：近代物理研究所

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