title: Na+/H+ exchanger 1 inhibition contributes to K562 leukaemic cell differentiation.
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.
authors.affiliation: 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.
authors.forename: Weina
authors.initials: W
authors.lastname: Jin
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Chang
authors.forename: Yani
authors.initials: Y
authors.lastname: Lin
authors.forename: Huawen
authors.initials: H
authors.lastname: Li
authors.forename: Lihong
authors.initials: L
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.forename: Tianxiang
authors.initials: T
authors.lastname: Pang
mesh_terms: D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D015687:Cell Hypoxia; D003035:Cobalt / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D020014:K562 Cells; D007938:Leukemia / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D027682:Cation Transport Proteins; D006146:Guanidines; D016209:Interleukin-8; D034741:RNA, Small Interfering; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; D003035:Cobalt; C093373:cariporide; D048051:p38 Mitogen-Activated Protein Kinases; C018021:cobaltous chloride