南方医科大学学报2017，Vol.37Issue(4)：537-541,5.DOI:10.3969/j.issn.1673-4254.2017.04.20
热疗中热休克蛋白90对26S蛋白酶体的调控机制
Mechanism of heat shock protein 90 for regulating 26S proteasome in hyperthermia
摘要
Abstract
Objective To investigate the mechanism by which heat shock protein 90 (HSP90) regulates 26S proteasome in hyperthermia. Methods Hyperthermic HepG2 cell models established by exposure of the cells to 42 ℃ for 3, 6, 12, and 24 h were examined for production of reactive oxygen species (ROS) and cell proliferation, and the changes in Hsp90α and 26S proteasome were analyzed. Results ROS production in the cells increased significantly after hyperthermia (F=28.958, P<0.001), and the cell proliferation was suppressed progressively as the heat exposure time extended (F=621.704, P<0.001). Hyperthermia up-regulated Hsp90α but decreased the expression level (F=164.174, P<0.001) and activity (F=133.043, P<0.001) of 26S proteasome. The cells transfected with a small interfering RNA targeting Hsp90α also showed significantly decreased expression of 26S proteasome (F=180.231, P<0.001). Conclusion The intracellular ROS production increases as the hyperthermia time extends. Heat stress and ROS together cause protein denature, leading to increased HSP90 consumption and further to HSP90 deficiency for maintaining 26S proteasome assembly and stability. The accumulation of denatured protein causes unfolded protein reaction in the cells to eventually result in cell death.关键词
热休克蛋白90/26S蛋白酶体/氧化应激/热疗Key words
heat shock protein 90/26S proteasome/oxidative stress/hyperthermia引用本文复制引用
马庆荣,余佩芝,张帆,李玉齐,杨曙,莫贤毅,莫凯岚,丁颖,陈斯泽..热疗中热休克蛋白90对26S蛋白酶体的调控机制[J].南方医科大学学报,2017,37(4):537-541,5.基金项目
广东省医学科学技术研究基金项目(A2014364) （A2014364）
