1 alpha,25-Dihydroxycholecalciferol and a human myeloid leukaemia cell line (HL-60).
1 alpha,25-Dihydroxycholecalciferol and a human myeloid leukaemia cell line (HL-60).
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1 α,25-二羟基胆钙化醇和人骨髓性白血病细胞系 (HL-60)。
DOI：
10.1042/bj2040713
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
T. Suda
中科院分区：
文献类型：
--
作者：
H. Tanaka;E. Abe;C. Miyaura;T. Kuribayashi;K. Konno;Y. Nishii;T. Suda
人早幼粒细胞白血病细胞（HL-60）可被胆钙化醇的活性形式1 α，25-二羟基胆钙化醇[1 α，25（OH）2D 3]体外诱导分化为成熟粒细胞。分化相关特性，如吞噬作用和C3玫瑰花结形成，诱导低至0.12 nM-1 α，25（OH）2D 3，在12 nM，约一半的细胞表现出分化的第3天的孵育。同时，活细胞数量减少至对照组的一半以下。在所检测的各种胆钙化醇衍生物中，1 α，25（OH）2D 3和1 α，24 R-二羟基胆钙化醇在诱导分化方面最有效，其次是1 α，24 S-二羟基胆钙化醇、1 α-羟基胆钙化醇、25-羟基胆钙化醇和24 R，25-二羟基胆钙化醇。在HL-60细胞中发现了与1 α，25（OH）2D 3特异性结合的胞浆蛋白。它的物理性质与在肠和甲状旁腺等靶组织中发现的非常相似。1 α，25（OH）2D 3结合到细胞质受体定量转移到染色质部分。胆钙化醇的各种衍生物在诱导分化的特异性与它们与细胞溶质受体的关联性密切相关。这些结果是相容的假设，即活性形式的胆钙化醇诱导分化的人髓性白血病细胞的机制类似于提出的经典概念的类固醇激素的作用。
Human promyelocytic leukaemia cells (HL-60) can be induced to differentiate into mature granulocytes in vitro by 1 alpha,25-dihydroxycholecalciferol [1 alpha,25(OH)2D3], the active form of cholecalciferol. The differentiation-associated properties, such as phagocytosis and C3 rosette formation, were induced by as little as 0.12 nM-1 alpha,25(OH)2D3, and, at 12 nM, about half of the cells exhibited differentiation on day 3 of incubation. Concomitantly the viable cell number was decreased to less than half of the control. Among various derivatives of cholecalciferol examined, 1 alpha,25(OH)2D3 and 1 alpha,24R-dihydroxycholecalciferol were the most potent in inducing differentiation, followed successively by 1 alpha,24S-dihydroxycholecalciferol, 1 alpha-hydroxycholecalciferol, 25-hydroxycholecalciferol and 24R,25-dihydroxycholecalciferol. A cytosol protein specifically bound to 1 alpha,25 (OH)2D3 was found in HL-60 cells. Its physical properties closely resembled those found in such target tissues as intestine and parathyroid glands. 1 alpha,25(OH)2D3 bound to the cytosol receptor was transferred quantitatively to the chromatin fraction. The specificity of various derivatives of cholecalciferol in inducing differentiation was well correlated with that of their association with the cytosol receptor. These results are compatible with the hypothesis that the active form of cholecalciferol induces differentiation of human myeloid leukaemia cells by a mechanism similar to that proposed for the classical concept of steroid hormone action.