Institutional Repository of Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, People's Republic of China
| Upregulation of NRF2 through autophagy/ERK 1/2 ameliorates ionizing radiation induced cell death of human osteosarcoma U-2 OS | |
Chen, Ni1,2; Zhang, Rui2 ; Konishi, Teruaki3; Wang, Jun2
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| 2017 | |
| 发表期刊 | MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
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| 摘要 | The antioxidative response mediated by transcription factor NRF2 is thought to be a pivotal cellular defense system against various extrinsic stresses. It has been reported that activation of the NRF2 pathway confers cells with resistance to ionizing radiation-induced damage. However, the underlying mechanism remains largely unknown. In the current research, it was found that a-particle radiation has the ability to stimulate NRF2 expression in human osteosarcoma U-2 OS cells. Knockdown of cellular NRF2 level by shRNA-mediated gene silencing decreased the survival rate, increased the micronucleus formation rate and apoptosis rate in irradiated cells. Consistently, knockdown of NRF2 resulted in decreased expression of p65 and Bcl-2, and increased expression of p53 and Bax. Besides, it was observed that increased expression of NRF2 was partially dependent on radiation induced phosphorylation of ERK 1/2. Further results showed that radiation promoted autophagy flux which leads to the enhanced phosphorylation of ERK 1/2, as evidenced by the resultls that knockdown of ATG5 (Autophagy protein 5) gene by shRNA suppressed both radiation induced ERK 1/2 phosphorylation and NRF2 upregulation. Based on these results, it is proposed that attenuation of NRF2 antioxidative pathway can sensitize U-2 OS cells to radiation, where NRF2 antioxidative response is regulated by autophagy mediated activation of ERK 1/2 kinases. (C) 2016 Elsevier B.V. All rights reserved. |
| 文章类型 | Article |
| 关键词 | Ionizing Radiation Autophagy Nrf2 Erk1/2 Radio-sensitization |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| DOI | 10.1016/j.mrgentox.2016.11.006 |
| 关键词[WOS] | ANTIOXIDANT RESPONSE ; CANCER-CELLS ; DNA-DAMAGE ; OXIDATIVE STRESS ; PATHWAY ; ACTIVATION ; TRANSCRIPTION ; MECHANISMS ; APOPTOSIS ; DIE |
| 收录类别 | SCI |
| 语种 | 英语 |
| 项目资助者 | Ministry of Science and Technology of China(2014GB112006) ; Ministry of Science and Technology of China(2014GB112006) ; Ministry of Science and Technology of China(2014GB112006) ; Ministry of Science and Technology of China(2014GB112006) ; National Natural Science Foundation of China(31370842 ; National Natural Science Foundation of China(31370842 ; National Natural Science Foundation of China(31370842 ; National Natural Science Foundation of China(31370842 ; 11575232) ; 11575232) ; 11575232) ; 11575232) |
| WOS研究方向 | Biotechnology & Applied Microbiology ; Genetics & Heredity ; Toxicology |
| WOS类目 | Biotechnology & Applied Microbiology ; Genetics & Heredity ; Toxicology |
| WOS记录号 | WOS:000391905000002 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.hfcas.ac.cn:8080/handle/334002/32791 |
| 专题 | 技术生物与农业工程研究所 |
| 作者单位 | 1.Univ Sci & Technol China, Sch Nucl Sci & Technol, Hefei 230027, Peoples R China 2.Chinese Acad Sci & Anhui Prov, Hefei Inst Phys Sci, Key Lab Ion Beam Bioengn, 350 Shushanhu Rd, Hefei 230031, Peoples R China 3.Natl Inst Radiol Sci, Int Open Lab, Chiba, Japan |
| 推荐引用方式 GB/T 7714 | Chen, Ni,Zhang, Rui,Konishi, Teruaki,et al. Upregulation of NRF2 through autophagy/ERK 1/2 ameliorates ionizing radiation induced cell death of human osteosarcoma U-2 OS[J]. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS,2017,813(无):10-17. |
| APA | Chen, Ni,Zhang, Rui,Konishi, Teruaki,&Wang, Jun.(2017).Upregulation of NRF2 through autophagy/ERK 1/2 ameliorates ionizing radiation induced cell death of human osteosarcoma U-2 OS.MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS,813(无),10-17. |
| MLA | Chen, Ni,et al."Upregulation of NRF2 through autophagy/ERK 1/2 ameliorates ionizing radiation induced cell death of human osteosarcoma U-2 OS".MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS 813.无(2017):10-17. |
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