Bhatia M, Kirkland J B, Meckling-Gill K A
Department of Nutritional Sciences, University of Guelph, Ontario, Canada.
J Biol Chem. 1995 Jul 7;270(27):15962-5. doi: 10.1074/jbc.270.27.15962.
We have shown that 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) primes NB4 cells, the only available acute promyelocytic leukemia cell line, for 12-O-tetradecanoyl-phorbol-13-acetate-induced monocytic differentiation. Here, we have used isomers of 1,25(OH)2D3 to investigate the role of 1,25(OH)2D3 and its putative nuclear receptor (VDR) in NB4 cell monocytic differentiation. 1 beta,25-dihydroxyvitamin D3 (HL), a specific antagonist of only the nongenomic signals of 1,25(OH)2D3, attenuated the priming effect of 1,25(OH)2D3. The 6-cis conformer of 1,25(OH)2D3 (HF), which is unable to bind to VDR, was 20 times more potent than 1,25(OH)2D3 as a priming agent for monocytic differentiation. This response was also blocked by the HL antagonist. Unlike myelocytic HL-60 cells, which respond to 1,25(OH)2D3 with increases in VDR expression and monocytic differentiation, neither HF nor 1,25(OH)2D3 regulated VDR expression in NB4 cells. In the monocytic differentiation of acute promyelocytic leukemia cells, 1,25(OH)2D3 appears to signal through a pathway independent of VDR/VDRE action.
我们已经证明，1,25-二羟基维生素D3（1,25-(OH)2D3）可使NB4细胞（唯一可用的急性早幼粒细胞白血病细胞系）对12-O-十四烷酰佛波醇-13-乙酸酯诱导的单核细胞分化产生致敏作用。在此，我们使用1,25(OH)2D3的异构体来研究1,25(OH)2D3及其假定的核受体（VDR）在NB4细胞单核细胞分化中的作用。1β,25-二羟基维生素D3（HL），一种仅针对1,25(OH)2D3非基因组信号的特异性拮抗剂，减弱了1,25(OH)2D3的致敏作用。1,25(OH)2D3的6-顺式构象异构体（HF）不能与VDR结合，作为单核细胞分化的致敏剂，其效力比1,25(OH)2D3高20倍。这种反应也被HL拮抗剂阻断。与髓细胞性HL-60细胞不同，后者对1,25(OH)2D3的反应是VDR表达增加和单核细胞分化，而HF和1,25(OH)2D3均不调节NB4细胞中的VDR表达。在急性早幼粒细胞白血病细胞的单核细胞分化中，1,25(OH)2D3似乎通过一条独立于VDR/VDRE作用的途径发出信号。
