Mechanism of HL-60 cells apoptosis induced by proteasome inhibitor MG132.
10.7534/j.issn.1009-2137.2013.04.019
- Author:
Yong-Ming ZHOU
1
;
Mei-Xia YU
;
Yu-Zhen QIU
;
Xiao-Lei XING
;
Chun-Hong YAO
;
Ru-Jun BAI
Author Information
1. Department of Hematology, Tianyou Hospital Affiliated to Wuhan University of Science and Technology, Wuhan 430064, China.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
drug effects;
Caspase 8;
metabolism;
Caspase 9;
metabolism;
Cyclin-Dependent Kinase Inhibitor p21;
metabolism;
Cyclin-Dependent Kinase Inhibitor p27;
metabolism;
HL-60 Cells;
Humans;
Leupeptins;
pharmacology;
Proteasome Inhibitors;
pharmacology
- From:
Journal of Experimental Hematology
2013;21(4):911-915
- CountryChina
- Language:Chinese
-
Abstract:
The purpose of this study was to elucidate the apoptosis, apoptotic pathway of HL-60 cells induced by proteasome inhibitor MG132 and its effect on allogeneic mixed lymphocyte reaction. Apoptosis of HL-60 cells was detected by flow cytometry, the expression of P21, P27 and P53 proteins in HL-60 cells treated with MG132 was assayed by Western blot. The HL-60 cells were treated with 1 µmol/L MG132 for 48 h, and irradiated by 75 Gy of (60)Co γ-ray, but their antigenicity was preserved. The effect of irradiated HL-60 cells treated with MG132 on proliferation of peripheral blood mononuclear cells (PBMNC) was measured by CCK-8 method. The results showed that the apoptotic rate of MG132-treated HL-60 cells increased in dose-and time-dependent manner. No significant changes in MG132-induced apoptosis were observed after inhibiting caspase-8 and caspase-9 pathway. The expression of P21 and P27 protein increased after treatment of HL-60 cells with MG132. CCK-8 test showed that HL-60 cells induced with low-dose of MG132 displayed the enhancing effect on proliferation of PBMNC. It is concluded that high dose of MG132 can induce the apoptosis of HL-60 cells, and has direct killing effect on HL-60 cells, but this inducing apoptotic effect on HL-60 cells can not be realized through caspase-8 and caspase-9 pathway. The P21 and P27 protein may be involved in MG132 induced HL-60 cell apoptosis. Low dose of MG132 promotes the proliferation of PBMNC in healthy individuals and enhance the immunity of organism.
