Batuman V, Sastrasinh M, Sastrasinh S
Kidney Int. 1986 Nov;30(5):662-5. doi: 10.1038/ki.1986.237.
Effect of varying concentrations (0 to 800 microM) of three different light chains on sodium-dependent L-(14C)alanine and D-(14C)glucose uptake by rat renal brush border membrane vesicles were studied. One kappa and two lambda type light chains (lambda-1 and lambda-2) were isolated from urines of patients with multiple myeloma. At maximal inhibitory concentrations the kappa chain reduced alanine uptake from 206 +/- 18 to 77 +/- 18 pmole/mg protein (P less than 0.005) and glucose uptake from 357 +/- 22 to 146 +/- 8 pmole/mg protein (P less than 0.001). lambda-1 reduced alanine uptake from 136 +/- 17 to 60 +/- 8 pmole/mg protein (P less than 0.005) and glucose uptake from 354 +/- 17 to 77 +/- 14 pmole/mg protein (P less than 0.001). lambda-2 reduced alanine uptake from 105 +/- 9 to 28 +/- 5 pmole/mg protein (P less than 0.001) and glucose uptake from 194 +/- 7 to 66 +/- 7 pmole/mg protein (P less than 0.001). The half maximal inhibitory concentrations (I50) of kappa, lambda-1 and lambda-2 light chains were 68, 76 and 140 microM for alanine uptake and 120, 70 and 105 microM for glucose uptake. Control experiments using bovine serum albumin and beta-lactoglobulin showed no inhibitory effect on alanine and glucose uptake by either protein. These data reveal brush border membrane effects by myeloma light chains and confirm that direct Bence Jones protein nephrotoxicity may play an important role in the pathogenesis of kidney dysfunction associated with multiple myeloma.
研究了三种不同轻链在不同浓度（0至800微摩尔）下对大鼠肾刷状缘膜囊泡钠依赖性L-(14C)丙氨酸和D-(14C)葡萄糖摄取的影响。从多发性骨髓瘤患者尿液中分离出一条κ链和两条λ型轻链（λ-1和λ-2）。在最大抑制浓度下，κ链使丙氨酸摄取量从206±18皮摩尔/毫克蛋白降至77±18皮摩尔/毫克蛋白（P<0.005），葡萄糖摄取量从357±22皮摩尔/毫克蛋白降至146±8皮摩尔/毫克蛋白（P<0.001）。λ-1使丙氨酸摄取量从136±17皮摩尔/毫克蛋白降至60±8皮摩尔/毫克蛋白（P<0.005），葡萄糖摄取量从354±17皮摩尔/毫克蛋白降至77±14皮摩尔/毫克蛋白（P<0.001）。λ-2使丙氨酸摄取量从105±9皮摩尔/毫克蛋白降至28±5皮摩尔/毫克蛋白（P<0.001），葡萄糖摄取量从194±7皮摩尔/毫克蛋白降至66±7皮摩尔/毫克蛋白（P<0.001）。κ、λ-1和λ-2轻链对丙氨酸摄取的半数最大抑制浓度（I50）分别为68、76和140微摩尔，对葡萄糖摄取的I50分别为120、70和105微摩尔。使用牛血清白蛋白和β-乳球蛋白的对照实验表明，这两种蛋白质对丙氨酸和葡萄糖摄取均无抑制作用。这些数据揭示了骨髓瘤轻链对刷状缘膜的影响，并证实直接的本-周蛋白肾毒性可能在与多发性骨髓瘤相关的肾功能障碍发病机制中起重要作用。
