Inhibition of NHE1 promotes hypoxia-induced differentiation of K562 leukemic cells.
- Author:
Wei-Na JIN
1
;
Jian WANG
;
Guo-Qiang CHANG
;
Ya-Ni LIN
;
Li-Hong WANG
;
Hua-Wen LI
;
Wei GAO
;
Qing-Hua LI
;
Tian-Xiang PANG
Author Information
1. State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
- Publication Type:Journal Article
- MeSH:
Cation Transport Proteins;
metabolism;
Cell Differentiation;
Cell Hypoxia;
Humans;
K562 Cells;
MAP Kinase Signaling System;
Sodium-Hydrogen Exchanger 1;
Sodium-Hydrogen Exchangers;
metabolism
- From:
Journal of Experimental Hematology
2011;19(3):661-665
- CountryChina
- Language:Chinese
-
Abstract:
This study was purposed to investigate the effect of hypoxia microenvironment on K562 leukemic cell differentiation, and characteristics of NHE1 involvement in this process. The K562 cells were treated with hypoxia-mimical agent CoCl₂ or under actual hypoxia culture, and the specific NHE1 inhibitor Cariporide was used to inhibit NHE1 activity. The fluorescent probe BCECF was used for pH(i) measurements. Gene expression was analyzed by RT-PCR. The morphological characteristics was determined by Wright's staining. Signaling pathways were detected by Western blot using phosphospecific antibodies. The results indicated that the hypoxia or mimetic hypoxia favored K562 cells differentiation with up-regulation of C/EBPα. Moreover, treatment with Cariporide under hypoxia synergistically enhanced leukemia cell differentiation. Treatment with Cariporide increased levels of phosphorylated ERK5 and P38 mitogen-activated protein kinase (MAPK). It is concluded that the hypoxia or mimetic hypoxia can induce the differentiation of K562 cells, the inhibition of NHE1 activity can promote the hypoxia-induced K562 cell differentiation. The enhancement of hypoxia-induced K562 differentiation by Cariporide via MAPK signal pathway suggests a possible therapeutic target of NHE1 under hypoxia microenvironment in the treatment of leukemias.
