Ladoux A, Abita J P, Geny B
Differentiation. 1986;33(2):142-7. doi: 10.1111/j.1432-0436.1986.tb00419.x.
The human promyelocytic leukemia cell line, HL-60, can be induced to differentiate into granulocyte-like cells when cultured in the presence of 10(-6) M retinoic acid (RA) for several days. Following the addition of RA two kinds of changes occur. First, there are early changes that comprise an increase in the intracellular concentration of sodium ions [Na]i, which reaches its maximum after 6 h, and an increase in the activity of the Na+-pump, which is reflected by an ouabain-sensitive K+ influx that peaks at 8 h (170% of the control value) and that occurs without any change in the number of pump molecules, as measured by the binding of 3H-ouabain. Second, beginning after 12 h of culture with RA, a decrease in the number of ouabain-binding sites occurs, this being accompanied by an increase in the number of K+ ions actively transported by each site. The effect of modulation of Na+-pump activity on the RA-induced differentiation of HL-60 cells was studied using low, noncytotoxic concentrations of ouabain which, although alone having no differentiating effect, accelerated and potentiated the effect of RA on differentiation. When added in combination, these drugs induced rapid stimulation of the Na+-pump, which reached its peak after 2 h. These results indicate that a concomitant increase in the level of [Na+]i and in the activity of the Na+-pump constitute primary events in the interaction between RA and HL-60 cells, and that cation fluxes may play a role in the initiation of the process of differentiation.
人早幼粒细胞白血病细胞系HL-60，在10^(-6) M视黄酸（RA）存在下培养数天时，可被诱导分化为粒细胞样细胞。加入RA后会发生两种变化。首先，出现早期变化，包括细胞内钠离子浓度[Na]i升高，6小时后达到最大值，以及钠泵活性增加，这表现为哇巴因敏感的钾离子内流增加，在8小时达到峰值（为对照值的170%），且通过3H-哇巴因结合测定，泵分子数量没有任何变化。其次，在加入RA培养12小时后开始，哇巴因结合位点数量减少，同时每个位点主动转运的钾离子数量增加。使用低浓度、无细胞毒性的哇巴因研究了钠泵活性调节对RA诱导HL-60细胞分化的影响，该浓度的哇巴因单独使用时没有分化作用，但能加速并增强RA对分化的作用。当联合添加时，这些药物可迅速刺激钠泵，2小时后达到峰值。这些结果表明，[Na+]i水平和钠泵活性的同时增加是RA与HL-60细胞相互作用的主要事件，阳离子通量可能在分化过程的启动中起作用。
