Asplin J R, Arsenault D, Parks J H, Coe F L, Hoyer J R
Department of Medicine, University of Chicago, Illinois, USA.
Kidney Int. 1998 Jan;53(1):194-9. doi: 10.1046/j.1523-1755.1998.00739.x.
Uropontin (UP) is known to inhibit the growth and nucleation of calcium oxalate monohydrate (COM) crystals, and it also impedes attachment of calcium oxalate crystals to cultured renal epithelial cells. However, its role in normal defense against renal crystallization, and in pathogenesis of nephrolithiasis is unclear. In this study we determined the effect of UP on aggregation of COM crystals as well as the inhibitory activity of UP on COM crystal growth and nucleation in a series of normal subjects, in order to assess the potential of UP as an important urinary inhibitor. The mean urinary excretion of UP measured by ELISA was 185 +/- 12 nmol/24 hr (mean +/- SEM) with a mean urine UP concentration of 131 +/- 13 nM. Uropontin isolated by immunoaffinity chromatography was a very potent inhibitor of COM crystal aggregation, with a mean UP concentration of 28 +/- 4 nM required for a 50% reduction in aggregation. The kDa for COM crystal growth inhibition determined from Langmuir type isotherms was 21 +/- 3 nM and the concentration required for 50% reduction in COM crystal growth rate was 16 +/- 2 nM. Inhibition of secondary nucleation was measured at a single concentration of 200 nM, which reduced the nucleation rate to 42 +/- 3% of control. Using a theoretical model of growth and aggregation inhibition at varying urine flow rates, we showed that inhibitory activity of UP would be significant for all subjects over a wide range of urine flow rates. Overall, UP is a potent inhibitor of COM aggregation as well as growth and nucleation. The urinary concentration of UP is in the range in which its contribution to inhibition of growth and aggregation are likely to be substantial. Thus, UP appears to be an important natural defense against renal crystallizations and nephrolithiasis.
已知尿桥蛋白（UP）可抑制一水草酸钙（COM）晶体的生长和成核，并且还能阻止草酸钙晶体附着于培养的肾上皮细胞。然而，其在正常防御肾结晶以及肾结石发病机制中的作用尚不清楚。在本研究中，我们测定了UP对COM晶体聚集的影响以及UP在一系列正常受试者中对COM晶体生长和成核的抑制活性，以评估UP作为一种重要尿抑制剂的潜力。通过酶联免疫吸附测定法测得的UP平均尿排泄量为185±12 nmol/24小时（平均值±标准误），平均尿UP浓度为131±13 nM。通过免疫亲和层析分离得到的尿桥蛋白是COM晶体聚集的一种非常有效的抑制剂，聚集减少50%所需的平均UP浓度为28±4 nM。根据朗缪尔等温线确定的COM晶体生长抑制的kDa为21±3 nM，COM晶体生长速率降低50%所需的浓度为16±2 nM。在单一浓度200 nM下测量二次成核的抑制情况，其将成核速率降低至对照的42±3%。使用不同尿流率下生长和聚集抑制的理论模型，我们表明在很宽的尿流率范围内，UP对所有受试者的抑制活性都将是显著的。总体而言，UP是COM聚集以及生长和成核的有效抑制剂。UP的尿浓度处于其对生长和聚集抑制作用可能很大的范围内。因此，UP似乎是预防肾结晶和肾结石的一种重要天然防御物质。
