期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 69, 期 -, 页码 239-248出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2014.01.034
关键词
TIGAR; TRX1 nuclear translocation; Oxidative stress; DNA damage repair; Radiosensitivity; Free radicals
资金
- National Natural Science Foundation of China [31270897, 30970842, 81271682]
- Graduate Education Innovation Project of Jiangsu Province
- Priority Academic Program Development of Jiangsu Higher Education Institutions
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. (c) 2014 Elsevier Inc. All rights reserved.
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