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.
Cell Biol Int. 2012 Aug 1;36(8):739-45. doi: 10.1042/CBI20100919.
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.
研究了低氧对慢性髓系白血病 K562 细胞分化的影响，以及 NHE1（钠离子/氢离子交换器 1）的作用。低氧诱导 K562 细胞分化，表现在形态特征的改变、C/EBPα（CCAAT/增强子结合蛋白α）的上调和显著的 IL-8（白细胞介素-8）释放。低氧下抑制 NHE1 还能提高 C/EBPα 的水平，并进一步促进白血病细胞分化。低氧条件下抑制 NHE1 后，p38 MAPK（丝裂原活化蛋白激酶）的药理学抑制也显著抑制了 C/EBPα 的表达。这些结果表明，NHE1 的抑制增强了低氧诱导的 K562 分化，这可能是由于 p38 MAPK 信号通路上调 C/EBPα，提示低氧微环境下 NHE1 可能成为治疗白血病的治疗靶点。
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