期刊名称：Journal of Nutritional Science and Vitaminology
印刷版ISSN：0301-4800
电子版ISSN：1881-7742
出版年度：1991
卷号：37
期号：Supplement
页码：S93-S103
DOI：10.3177/jnsv.37.Supplement_S93
出版社：Center for Academic Publications Japan
摘要：The mechanism by which resistance to 1, 25 dihydroxyvitamin D3 (1, 25-(OH)2D3) occurs in patients with chronic renal failure was studied. This agent induces differentiation and 1, 25-(OH)2D3-24-hydroxylase activity in the mitochondria of the human promyelocytic leukemia cell line, HL-60, via a steroid-hormone receptor mechanism. HL-60 cells were cultured in RPMI 1640 medium supplemented with 10% normal or uremic serum. Treatment of these cells with 10-8M 1, 25-(OH)2D3 for 5 days in a medium containing 10% uremic serum from 4 patients with chronic renal failure resulted in a maturation of the cells amounting to 30.3 ± 18.7% (mean ± SD) and 32.5 ± 11.2%, as obtained by NBT reduction assay and NSE assay, respectively. These values were significantly lower than those obtained with 10% serum from 3 normal controls (66.6 ± 12.8%, 58.3 ± 10.9%, p <0.02). The treatment of HL-60 cells with 1, 25-(OH)2D3 in a mixture of 5% normal plus 5% uremic serum caused cell differentiation to an extent similar to that in 10% uremic serum, which suggests the presence of a substance(s) having 1, 25-(OH)2D3-inhibitory activity in the uremic serum. Exposure of HL-60 cells to uremic serum significantly impaired their responsiveness to 1, 25-(OH)2D3 as assessed by the induction of the cell's ability to hydroxylate the C-24 position of 1, 25-(OH)2 [3H] D3. The mechanism by which uremic serum confers an impaired cellular response to 1, 25-(OH)2D3 seemed to be due, in part, to a decrease in 1, 25-(OH)2D3 receptor levels. A significant positive correlation was observed between intracellular cAMP levels and 1, 25-(OH)2D3-induced HL-60 cell maturation. In summary, the mechanism by which uremic serum confers 1, 25-(OH)2D3 resistance upon HL-60 cells seemed to be due to the presence of 1, 25-(OH)2D3-inhibitory activity in uremic serum, which may modulate cellular responsiveness to 1, 25-(OH)2D3 by such mechanisms as reducing 1, 25-(OH)2D3 receptor levels in the cells, in part through alteration in cAMP metabolism.
