|Cancer||Cell death||Cell cycle||Cytoskeleton||Exo/endocytosis||Differentiation||Division||Organelles||Signalling||Stem cells||Trafficking|
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* and Tianxiang Pang*1
*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, and †Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Anshan Road 154, Tianjin 300052, Peoples Republic of China
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.
Key words: CCAAT/enhancer-binding protein α, differentiation, hypoxia, intracellular pH, mitogen-activated protein kinase, Na+/H+ exchanger 1
Abbreviations: AML, acute myeloid leukaemia, BCECF-AM, 2′,7′-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl, C/EBPα, CCAAT/enhancer-binding protein α, CML, chronic myeloid leukaemia, CML-BC, CML blast crisis, CXCL, CXC chemokine ligand, ERK, extracellular-signal-regulated kinase, FBS, fetal bovine serum, GAPDH, glyceraldehyde-3-phosphate dehydrogenase, IL, interleukin, JNK, c-Jun N-terminal kinase, MAPK, mitogen-activated protein kinase, MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide, NCF1, neutrophil cytosolic factor 1, NHE1, Na+/H+ exchanger 1, ORM1, orosomucoid 1, pHi, intracellular pH, siRNA, small interfering RNA
1To whom correspondence should be addressed (email email@example.com).
Received 29 December 2010/2 March 2012; accepted 12 April 2012
Published as Cell Biology International Immediate Publication 12 April 2012, doi:10.1042/CBI20100919
© The Author(s) Journal compilation © 2012 International Federation for Cell Biology