首页> 外文期刊>American Journal of Physiology >Ficoll and dextran vs. globular proteins as probes for testing glomerular permselectivity: effects of molecular size, shape, charge, and deformability.
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Ficoll and dextran vs. globular proteins as probes for testing glomerular permselectivity: effects of molecular size, shape, charge, and deformability.

机译:Ficoll和右旋糖酐vs.球状蛋白作为测试肾小球通透性的探针:分子大小,形状,电荷和可变形性的影响。

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Polydisperse mixtures of dextran or Ficoll have been frequently used as molecular probes for studies of glomerular permselectivity because they are largely inert and not processed (reabsorbed) by the proximal tubules. However, dextrans are linear, flexible molecules, which apparently are hyperpermeable across the glomerular barrier. By contrast, the Ficoll molecule is almost spherical. Still, there is ample evidence that Ficoll fractional clearances (sieving coefficients) across the glomerular capillary wall (GCW) are markedly higher than those for neutral globular proteins of an equivalent in vitro Stokes-Einstein (SE) radius. Physical data, obtained by "crowding" experiments or measurements of intrinsic viscosity, suggest that the Ficoll molecule exhibits a rather open, deformable structure and thus deviates from an ideally hard sphere. This is also indicated from the relationship between (log) in vitro SE radius and (log) molecular weight (MW). Whereas globular proteins seem to behave in a way similar to hydrated hard spheres, polydisperse dextran and Ficoll exhibit in vitro SE radii that are much larger than those for compact spherical molecules of equivalent MW. For dextran, this can be partially explained by a high-molecular-size asymmetry. However, for Ficoll the explanation may be that the Ficoll molecule is more flexible (deformable) than are globular proteins. An increased compressibility of Ficoll and an increased deformability and size asymmetry for dextran may be the explanation for the fact that the permeability of the GCW is significantly higher when assessed using polysaccharides such as Ficoll or dextran compared with that obtained using globular proteins as molecular size probes. We suggest that molecular deformability, besides molecular size, shape, and charge, plays a crucial role in determining the glomerular permeability to molecules of different species.
机译:右旋糖酐或Ficoll的多分散混合物经常被用作研究肾小球通透性的分子探针,因为它们在很大程度上是惰性的,并且不会被近端小管处理(再吸收)。然而,右旋糖酐是线性的柔性分子,显然在肾小球屏障上是高渗透性的。相反,Ficoll分子几乎是球形的。仍然有足够的证据表明,跨肾小球毛细血管壁(GCW)的Ficoll分数清除率(筛分系数)明显高于等效的体外Stokes-Einstein(SE)半径的中性球状蛋白质的清除率。通过“拥挤”实验或特性粘度测量获得的物理数据表明,Ficoll分子表现出相当开放,可变形的结构,因此偏离了理想的硬球体。从(log)体外SE半径和(log)分子量(MW)之间的关系也表明了这一点。球形蛋白的行为似乎类似于水合硬球,而多分散右旋糖酐和Ficoll的体外SE半径要比等分子量的紧凑球形分子大得多。对于右旋糖酐,这可以通过高分子大小的不对称性来部分解释。但是,对于Ficoll,可能的解释是Ficoll分子比球状蛋白更灵活(可变形)。 Ficoll的可压缩性增加,葡聚糖的可变形性和尺寸不对称性增加,可能解释了这样的事实:与使用球形蛋白质作为分子大小探针获得的多糖相比,使用Ficoll或dextran等多糖评估时,GCW的渗透性明显更高。我们建议,分子的可变形性,除了分子的大小,形状和电荷外,在决定肾小球对不同物种分子的渗透性中起着至关重要的作用。

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