Batuman V, Guan S, O'Donovan R, Puschett J B
Department of Medicine, Tulane University School of Medicine, New Orleans, La.
Ren Physiol Biochem. 1994 Nov-Dec;17(6):294-300. doi: 10.1159/000173861.
Primary cultures of cells derived from the rat proximal tubule were exposed to up to 200 microM lambda- or kappa-light chain obtained from myeloma patients. Light chains inhibited the uptake of both phosphate and glucose by the cells while albumin had no effect. The half-maximal inhibitory concentration (IC50) of both the lambda- and kappa-light chains on phosphate transport were similar, 34 and 35 microM respectively. The IC50 of the kappa-light chain on glucose transport was 360 microM. The inhibitory effect of light chains was dose-dependent (r = 0.90, p < 0.01 for the lambda-light chain and r = 0.93, p < 0.001 for the kappa-light chain, on phosphate transport; and r = 0.93, p < 0.001 for glucose transport). Dixon and Line-weaver-Burk plot analyses were characteristic for noncompetitive inhibition. The inhibition constant 89 microM for phosphate uptake derived from the Dixon plot was similar to the IC50 calculated from the dose-response curves. These findings indicate that light chains, at concentrations found in the tubule fluid of a typical myeloma patient, are potent inhibitors of phosphate and glucose transport in proximal tubular cells, and that direct cell toxicity is a major mechanism of light chain nephrotoxicity.
将源自大鼠近端小管的细胞原代培养物暴露于高达200微摩尔的、从骨髓瘤患者获得的λ或κ轻链中。轻链抑制细胞对磷酸盐和葡萄糖的摄取，而白蛋白则无此作用。λ和κ轻链对磷酸盐转运的半数最大抑制浓度（IC50）相似，分别为34和35微摩尔。κ轻链对葡萄糖转运的IC50为360微摩尔。轻链的抑制作用呈剂量依赖性（对于磷酸盐转运，λ轻链r = 0.90，p < 0.01；κ轻链r = 0.93，p < 0.001；对于葡萄糖转运，r = 0.93，p < 0.001）。Dixon和Line-weaver-Burk图分析具有非竞争性抑制的特征。从Dixon图得出的磷酸盐摄取抑制常数89微摩尔与从剂量反应曲线计算出的IC50相似。这些发现表明，在典型骨髓瘤患者肾小管液中发现的浓度下，轻链是近端肾小管细胞中磷酸盐和葡萄糖转运的有效抑制剂，并且直接细胞毒性是轻链肾毒性的主要机制。
