Inaba M, Otani S, Matsui-Yuasa I, Yukioka K, Nishizawa Y, Ishimura E, Morisada S, Yukioka M, Morisawa S, Morii H
Endocrinology. 1986 May;118(5):1849-55. doi: 10.1210/endo-118-5-1849.
The human promyelocytic leukemia cell line, HL-60, differentiated into macrophage/monocytes in the presence of 1 alpha,25-dihydroxycholecalciferol [1 alpha,25(OH)2D3], as assessed by the percentage of morphologically mature cells and their ability to reduce nitroblue tetrazolium. In this study of the mechanism involved, the activities of ornithine decarboxylase and spermidine/spermine-N1-acetyltransferase (SAT), the rate-limiting enzymes of polyamine metabolism, as well as the cellular levels of polyamine were measured. ODC activity reached a peak 24 h after the addition of 1 alpha,25(OH)2D3 and then decreased, while SAT activity gradually increased as differentiation commenced. An increase in putrescine and decreases in spermidine and spermine were also observed. Addition of alpha-difluoromethylornithine, an irreversible inhibitor of ODC, with or without methylglyoxalbis(guanylhydrazone), an inhibitor of S-adenosylmethionine decarboxylase, caused no effect on 1 alpha,25(OH)2D3-induced cell differentiation, although the cellular levels of putrescine and spermidine decreased markedly. Addition of alpha-difluoromethylornithine markedly suppressed cell proliferation; this effect was reversed by the addition of exogenous putrescine. Addition of exogenous spermidine or spermine to overcome activation of SAT also had no effect on 1 alpha,25(OH)2D3-induced cell differentiation. These results suggest both that polyamine metabolism is not important in 1 alpha,25(OH)2D3-induced differentiation of HL-60 cells, but that it is intimately involved in the proliferation of these cells.
人早幼粒细胞白血病细胞系HL - 60在1α,25 - 二羟胆钙化醇[1α,25(OH)₂D₃]存在的情况下分化为巨噬细胞/单核细胞，这是通过形态学成熟细胞的百分比及其还原硝基蓝四唑的能力来评估的。在这项关于所涉及机制的研究中，测定了鸟氨酸脱羧酶和亚精胺/精胺 - N1 - 乙酰转移酶（SAT）的活性，这两种酶是多胺代谢的限速酶，同时还测定了细胞内多胺的水平。在添加1α,25(OH)₂D₃后24小时，ODC活性达到峰值，然后下降，而随着分化开始，SAT活性逐渐增加。还观察到腐胺增加，亚精胺和精胺减少。添加α - 二氟甲基鸟氨酸（一种ODC的不可逆抑制剂），无论是否添加甲基乙二醛双（脒腙）（一种S - 腺苷甲硫氨酸脱羧酶抑制剂），对1α,25(OH)₂D₃诱导的细胞分化均无影响，尽管细胞内腐胺和亚精胺水平显著降低。添加α - 二氟甲基鸟氨酸显著抑制细胞增殖；添加外源性腐胺可逆转这种作用。添加外源性亚精胺或精胺以克服SAT的激活对1α,25(OH)₂D₃诱导的细胞分化也无影响。这些结果表明，多胺代谢在1α,25(OH)₂D₃诱导的HL - 60细胞分化中并不重要，但它与这些细胞的增殖密切相关。
