Na+/H+ exchanger 1 inhibition contributes to K562 leukaemic cell differentiation.

Weina Jin, Qinghua Li, Jian Wang, Guoqiang Chang, Yani Lin, Huawen Li, Lihong Wang, Wei Gao, Tianxiang Pang

Journal: Cell biology international 2012;36(8):739-45

PMID: 22494070

Abstract

The effect of hypoxia on the differentiation of chronic myeloid leukaemic K562 cells were studied, as was the role of the NHE1 (Na+/H+ exchanger 1). Hypoxia induced differentiation of K562 cells as seen by modifications in their morphological features, up-regulation of C/EBPα (CCAAT/enhancer-binding protein α), and marked IL-8 (interleukin-8) release. Inhibition of NHE1 under hypoxia additionally enhanced the level of C/EBPα and further promoted leukaemic cells differentiation. Pharmacological inhibition of p38 MAPK (mitogen-activated protein kinase) also significantly suppressed C/EBPα expression under hypoxia conditions after NHE1 inhibition. These results indicate the enhancement of hypoxia-induced K562 differentiation by NHE1 inhibition, which may be due to up-regulation of C/EBPα via p38 MAPK signalling pathway, which suggests a possible therapeutic target of NHE1 under hypoxia microenvironment in the treatment of leukaemic diseases.

Address: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing Road 288, Tianjin 300020, Peoples Republic of China.

DOI: 10.1042/CBI20100919

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MeSH Terms: CCAAT-Enhancer-Binding Protein-alpha, Cation Transport Proteins, Cell Differentiation, Cell Hypoxia, Cobalt, Guanidines, Humans, Hydrogen-Ion Concentration, Interleukin-8, K562 Cells, Leukemia, RNA Interference, RNA, Small Interfering, Signal Transduction, Sodium-Hydrogen Exchanger 1, Sodium-Hydrogen Exchangers, Sulfones, Up-Regulation, p38 Mitogen-Activated Protein Kinases