Upregulation of NRF2 through autophagy/ERK 1/2 ameliorates ionizing radiation induced cell death of human osteosarcoma U-2 OS

doi:10.1016/j.mrgentox.2016.11.006

CORC > 合肥物质科学研究院 > 中国科学院合肥物质科学研究院 > 技术生物与农业工程研究所

	Upregulation of NRF2 through autophagy/ERK 1/2 ameliorates ionizing radiation induced cell death of human osteosarcoma U-2 OS
	Chen, Ni 1,2; Zhang, Rui 2; Konishi, Teruaki 3; Wang, Jun2
刊名	MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
	2017
卷号	813 期号:无页码:10-17
关键词	Ionizing Radiation Autophagy Nrf2 Erk1/2 Radio-sensitization
DOI	10.1016/j.mrgentox.2016.11.006
文献子类	Article
英文摘要	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.
WOS关键词	ANTIOXIDANT RESPONSE ; CANCER-CELLS ; DNA-DAMAGE ; OXIDATIVE STRESS ; PATHWAY ; ACTIVATION ; TRANSCRIPTION ; MECHANISMS ; APOPTOSIS ; DIE
WOS研究方向	Biotechnology & Applied Microbiology ; Genetics & Heredity ; Toxicology
语种	英语
WOS记录号	WOS:000391905000002
资助机构	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) ; 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)
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/32791]
专题	合肥物质科学研究院_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.