Apoptosis Induction by Iron Radiation via Inhibition of Autophagy in Trp53(+/-) Mouse Testes: Is Chronic Restraint-Induced Stress a Modifying Factor?
文献类型:期刊论文
作者 | Li, Hongyan1,2,3; Wang, Bing4; Zhang, Hong1,2,3,5; Katsube, Takanori4; Xie, Yi1,2,3; Gan, Lu1,2,3 |
刊名 | INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES |
出版日期 | 2018 |
卷号 | 14页码:1109-1121 |
ISSN号 | 1449-2288 |
关键词 | Chronic restraint-induced stress iron ion radiation autophagy endoplasmic reticulum stress |
DOI | 10.7150/ijbs.22805 |
英文摘要 | We used chronic restraint-induced stress (CRIS) and iron ionizing radiation (IR) to mimic human exposure to psychological stress (PS) and IR in a mouse model, and to investigate the relationship among endoplasmic reticulum stress (ERS), apoptosis and autophagy in testicular toxicity. Male Trp53(+/-)C57BL/6N mice were restrained for 6 h/day for 28 consecutive days, and total body irradiation with 0.1 or 2 Gy iron ion beam was performed on the day 8. Histopathological observation showed severely damaged spermatogenic cells, increased apoptotic cells, caspase-3 activation and cytochrome c release, indicating that IR and CRIS+IR induced testicular cell apoptosis. Upregulation of GRP78 (78-kDa glucose-regulated protein) suggested that IR and CRIS+IR induced ERS in the testes, and further analysis showed that apoptosis was enhanced by ERS through activation of the PERK/eIF2 alpha/ATF4/CHOP pathway. Decreased expression of LC3II, Atg5 (autophagy related 5) and Beclin 1, and increased expression of p62, combined with ultrastructural changes seen under transmission electron microscopy, suggest that IR and CRIS+IR inhibit autophagosome formation. This process was related to inhibition of autophagy via activation of the PI3K/AKT/mTOR pathway under ERS. We showed that apoptosis was strengthened and autophagy was inhibited by ERS in mouse testes induced by IR and CRIPS+IR. These results showed that CRIS+IR had no difference in apoptosis induction and autophagy inhibition compared with IR alone. CIRS alone could induce apoptosis only in Leydig cells and its induction of pathological and molecular changes in testicular tissues was only a small extent as compared to those induced by IR. Of note, we showed that 28 consecutive days of CRIS did not exacerbate IR effects (no additive effect with IR). These findings also suggest that studies on the concurrent exposure to PS and IR should be done using different endpoints in both short and long-term CRIS models. |
WOS关键词 | ENDOPLASMIC-RETICULUM STRESS ; PSYCHOLOGICAL STRESS ; ION RADIATION ; PI3K/AKT/MTOR PATHWAY ; SIGNALING PATHWAY ; CELLS ; MICE ; SPERMATOGENESIS ; PROLIFERATION ; EXPRESSION |
资助项目 | National Natural Science Foundation of China[U1432248] ; National Natural Science Foundation of China[11505244] ; Ministry of Science and Technology National Key RD project[2016YFC0904 600] ; CAS |
WOS研究方向 | Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics |
语种 | 英语 |
出版者 | IVYSPRING INT PUBL |
WOS记录号 | WOS:000441906600001 |
资助机构 | National Natural Science Foundation of China ; Ministry of Science and Technology National Key RD project ; CAS |
源URL | [http://119.78.100.186/handle/113462/59278] |
专题 | 中国科学院近代物理研究所 |
作者单位 | 1.Chinese Acad Sci, Inst Modern Phys, Dept Radiat Med, Lanzhou 730000, Gansu, Peoples R China 2.Chinese Acad Sci, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou 730000, Gansu, Peoples R China 3.Key Lab Basic Res Heavy Ion Radiat Applicat Med, Lanzhou 730000, Gansu, Peoples R China 4.Natl Inst Quantum & Radiol Sci & Technol, Natl Inst Radiol Sci, Chiba 2638555, Japan 5.Gansu Wuwei Tumor Hosp, Dept Sci & Technol, Wuwei 733000, Peoples R China |
推荐引用方式 GB/T 7714 | Li, Hongyan,Wang, Bing,Zhang, Hong,et al. Apoptosis Induction by Iron Radiation via Inhibition of Autophagy in Trp53(+/-) Mouse Testes: Is Chronic Restraint-Induced Stress a Modifying Factor?[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,2018,14:1109-1121. |
APA | Li, Hongyan,Wang, Bing,Zhang, Hong,Katsube, Takanori,Xie, Yi,&Gan, Lu.(2018).Apoptosis Induction by Iron Radiation via Inhibition of Autophagy in Trp53(+/-) Mouse Testes: Is Chronic Restraint-Induced Stress a Modifying Factor?.INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,14,1109-1121. |
MLA | Li, Hongyan,et al."Apoptosis Induction by Iron Radiation via Inhibition of Autophagy in Trp53(+/-) Mouse Testes: Is Chronic Restraint-Induced Stress a Modifying Factor?".INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 14(2018):1109-1121. |
入库方式: OAI收割
来源:近代物理研究所
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