title: Radiosensitization of glioma cells by TP53-induced glycolysis and apoptosis regulator knockdown is dependent on thioredoxin-1 nuclear translocation.
abstract: TP53-induced glycolysis and apoptosis regulator (TIGAR) knockdown is proven to radiosensitize glioma cells, but the mechanisms are not fully understood. Thioredoxin-1 (TRX1) is a redox-sensitive oxidoreductase, which plays critical roles in DNA damage signal transduction via nuclear translocation in irradiated cells. Because the TRX1-dependent DNA damage signaling pathway relies on NADPH to maintain the reduced state of TRX1, and TIGAR functions to increase NADPH generation under oxidative stress, in this study, the role of TRX1 in TIGAR abrogation-induced radiosensitization was investigated. It was demonstrated that ionizing radiation (IR)-induced nuclear translocation of TRX1 was significantly inhibited by TIGAR interference and reversed by wild-type (WT)-TRX1 overexpression. In addition, WT-TRX1 overexpression could accelerate the process of DNA damage repair postponed by TIGAR knockdown in irradiated glioma cells. The reduction process of IR-oxidized TRX1 was also delayed by TIGAR knockdown but restored by WT-TRX1 overexpression. Therefore, we conclude that TIGAR knockdown-induced radiosensitization of glioma cells may be dependent on the inhibition of TRX1 nuclear translocation.
authors: Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences, Suzhou, Jiangsu 215006, China; Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, Jiangsu 215006, China.
authors: Haowen
authors: H
authors: Zhang
authors: Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences, Suzhou, Jiangsu 215006, China.
authors: Cheng
authors: C
authors: Gu
authors: Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences, Suzhou, Jiangsu 215006, China.
authors: Jiahua
authors: J
authors: Yu
authors: Department of Radiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200240, China.
authors: Zhongmin
authors: Z
authors: Wang
authors: Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences, Suzhou, Jiangsu 215006, China.
authors: Xiaopeng
authors: X
authors: Yuan
authors: Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences, Suzhou, Jiangsu 215006, China.
authors: Lei
authors: L
authors: Yang
authors: Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences, Suzhou, Jiangsu 215006, China.
authors: Jie
authors: J
authors: Wang
authors: Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences, Suzhou, Jiangsu 215006, China.
authors: Yanshuang
authors: Y
authors: Jia
authors: Department of Nuclear Medicine, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200240, China. Electronic address: nuclearj@163.com.
authors: Jianjun
authors: J
authors: Liu
authors: Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences, Suzhou, Jiangsu 215006, China. Electronic address: fangsh@suda.edu.cn.
authors: Fenju
authors: F
authors: Liu
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D004249:DNA Damage / Q000235:genetics; D005609:Free Radicals / Q000378:metabolism; D005910:Glioma / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D051379:Mice; D009154:Mutation; D018384:Oxidative Stress / Q000528:radiation effects; D010744:Phosphoric Monoester Hydrolases; D021381:Protein Transport / Q000235:genetics; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics*; D011839:Radiation, Ionizing; D015398:Signal Transduction / Q000235:genetics; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D005609:Free Radicals; D011506:Proteins; C515559:Txn1 protein, mouse; D013879:Thioredoxins; D010744:Phosphoric Monoester Hydrolases; C554952:TIGAR protein, mouse
keywords: DNA damage repair; Free radicals; Oxidative stress; Radiosensitivity; TIGAR; TRX1 nuclear translocation