Ness W, Kaiser H W, Drenckhahn D
Institute of Anatomy, University of Würzburg, Germany.
Histochem Cell Biol. 1998 Feb;109(2):175-80. doi: 10.1007/s004180050215.
Hypertension and kidney dysfunction in sodium transport observed in the Milan hypertensive strain (MHS) of rats are genetically associated with point mutations of adducin, an actin- and spectrin-binding protein of the membrane cytoskeleton. Polymorphism in the adducin locus has been reported to occur also in cases of human primary hypertension. In this study we show by immunostaining that adducin is localized along the basolateral epithelial membrane surface of the entire proximal and distal tubule with no detectable differences between MHS rats and the normotensive control strain (MNS). However, the total amount of adducin in kidney homogenates is reduced by about 45% in MHS rats as determined by quantitative immunoblotting. In erythrocyte membranes of MHS rats, adducin is reduced approximately 10%. The reduction of renal adducin in MHS rats is mainly caused by a reduction of the adducin pool that is loosely associated with kidney membranes and can be released by the non-ionic detergent, Triton X-100. The Triton-resistant, tightly membrane-bound pool of renal adducin differed by approximately 10% between MHS and MNS rats. Since several ion transporters have been shown to be tethered to the membrane cytoskeleton, we suppose that the reduction of the dynamic, loosely bound pool of adducin in MHS rats might interfere with the normal turnover and incorporation of yet unknown transporters involved in kidney sodium transport. However, the Na+,K+-ATPase appears to be not involved, as indicated by normal distribution and amounts of NA+,K+-ATPase in the kidney of MHS rats revealed by immunostaining and immunoblotting.
在大鼠米兰高血压品系（MHS）中观察到的钠转运相关的高血压和肾功能障碍与内收蛋白的点突变存在遗传关联，内收蛋白是一种膜细胞骨架中与肌动蛋白和血影蛋白结合的蛋白质。据报道，内收蛋白基因座的多态性也出现在人类原发性高血压病例中。在本研究中，我们通过免疫染色表明，内收蛋白定位于整个近端和远端小管的基底外侧上皮膜表面，MHS大鼠与正常血压对照品系（MNS）之间未检测到差异。然而，通过定量免疫印迹法测定，MHS大鼠肾匀浆中内收蛋白的总量减少了约45%。在MHS大鼠的红细胞膜中，内收蛋白减少了约10%。MHS大鼠肾内收蛋白的减少主要是由于与肾膜松散结合的内收蛋白池减少所致，这种内收蛋白池可被非离子去污剂Triton X-100释放。MHS大鼠和MNS大鼠之间，对Triton有抗性的、紧密结合于膜的肾内收蛋白池相差约10%。由于已证明几种离子转运蛋白与膜细胞骨架相连，我们推测MHS大鼠中动态的、松散结合的内收蛋白池的减少可能会干扰参与肾钠转运的未知转运蛋白的正常周转和整合。然而，免疫染色和免疫印迹显示，MHS大鼠肾中Na +，K + -ATP酶的分布和含量正常，表明Na +，K + -ATP酶似乎未参与其中。
