Mechanism of heat shock protein 90 for regulating 26S proteasome in hyperthermia
10.3969/j.issn.1673-4254.2017.04.20
- VernacularTitle:热疗中热休克蛋白90对26S蛋白酶体的调控机制
- Author:
Qingrong MA
1
;
Peizhi YU
;
Fan ZHANG
;
Yuqi LI
;
Shu YANG
;
Xianyi MO
;
Kailan MO
;
Ying DING
;
Size CHEN
Author Information
1. 广东药科大学附属第一医院胸外科
- Keywords:
heat shock protein 90;
26S proteasome;
oxidative stress;
hyperthermia
- From:
Journal of Southern Medical University
2017;37(4):537-541
- CountryChina
- Language:Chinese
-
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.
