Possible mechanism of action of the histone deacetylase inhibitors for the induction of differentiation of HL-60 clone 15 cells into eosinophils
Possible mechanism of action of the histone deacetylase inhibitors for the induction of differentiation of HL-60 clone 15 cells into eosinophils
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DOI：
10.1038/sj.bjp.0705869
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发表时间：
2004-07-01
影响因子：
7.3
通讯作者：
Ohuchi, K
中科院分区：
文献类型：
--
作者：
Ishihara, K;Hong, JJ;Ohuchi, K
我们已经检测了组蛋白去乙酰化酶抑制剂apicidin、TSA和n-丁酸盐对组蛋白乙酰化和人嗜酸性粒细胞白血病HL-60克隆15细胞向嗜酸性粒细胞分化的影响。2用apicidin（100 nm）、TSA（30 nm）或n-丁酸盐（500 μ M）孵育的细胞的活力没有显著变化，但更高浓度的阿皮西丁（大于或等于300 nM）或TSA（大于或等于100 nM）在第1.3天检测时降低了存活力Apicidin（100 nM）以及正丁酸盐（500 μ M）诱导了组蛋白H3上的历史H4和赖氨酸（14）残基的连续乙酰化，而TSA（30 nm）诱导短暂乙酰化。4孵育6天后，由Luxol-fast-blue染色的嗜酸性细胞由apicidin（100 nm）和n-丁酸盐（500 μ m）产生，但不由TSA（30 nm）产生。分化为嗜酸性粒细胞的其他标志物，如细胞内结构的变化，以及整合素β 7和主要碱性蛋白的表达，5 TSA（30 nm）反复处理H4细胞，可使H4细胞连续乙酰化。在第6天检查时，间隔12小时连续三次以上诱导了这种变化。此外，通过缩短与apicidin（100 nM）或n-丁酸盐（500 μ M）的孵育时间来削弱诱导。6 CCAAT/增强子结合蛋白被apicidin（100 nM）和n-丁酸盐（500 μ M）连续激活，但被TSA（30 nM）瞬时激活这些发现表明，H3和H4的连续乙酰化是HL-60克隆15细胞分化为嗜酸性粒细胞所必需的。
I We have examined the effect of the histone deacetylase inhibitors apicidin, trichostatin A (TSA) and n-butyrate on the histone acetylation and the differentiation of human eosinophilic leukemia HL-60 clone 15 cells into eosinophils.2 Viability of the cells incubated with apicidin (100 nm), TSA (30 nm) or n-butyrate (500 muM) did not change significantly, but higher concentrations of apicidin (greater than or equal to 300 nM) or TSA (greater than or equal to 100 nM) decreased the viability when examined at day 1.3 Apicidin (100 nM) as well as n-butyrate (500 muM) induced continuous acetylations of historic H4 and lysine(14) residue on histone H3, while TSA (30 nm) induced transient acetylations.4 After 6 days incubation, eosinophilic cells stained by Luxol-fast-blue were generated by apicidin (100 nm) and n-butyrate (500 pm) but not by TSA (30 nm). Other markers for differentiation into eosinophils such as changes in intracellular structure, and expressions of integrin beta7 and major basic protein, and the inhibition of cell proliferation were also induced by apicidin and n-butyrate but not by TSA.5 Continuous acetylation of historic H4 achieved by repeated treatment with TSA (30 nm) at an interval of 12 h for more than three times induced such changes when examined on day 6. In addition, the induction was impaired by shortening the period of incubation with apicidin (100 nm) or n-butyrate (500 muM).6 CCAAT/enhancer binding protein was continuously activated by apicidin (100 nM) and n-butyrate (500 muM), but was transiently activated by TSA (30 nM).7 These findings suggest that the continuous acetylation of histories H3 and H4 is necessary for the differentiation of HL-60 clone 15 cells into eosinophils.