Yamaguchi I, Hasegawa K, Takahashi N, Gejyo F, Naiki H
Department of Pathology, Fukui Medical University, Fukui 910-1193, Japan.
Biochemistry. 2001 Jul 24;40(29):8499-507. doi: 10.1021/bi0027128.
beta 2-Microglobulin-related (A beta 2M) amyloidosis is a common and serious complication in patients on long-term hemodialysis, and beta 2-microglobulin (beta 2-m) is a major structural component of A beta 2M amyloid fibrils. Fluorescence spectroscopic analysis with thioflavin T and electron microscopic study revealed that A beta 2M amyloid fibrils readily depolymerize into monomeric beta 2-m at a neutral to basic pH. Circular dichroism analysis revealed that soon after the initiation of the depolymerization reaction at pH 7.5, the characteristic spectrum of beta 2-m in A beta 2M amyloid fibrils changes to resemble that of monomeric beta 2-m at pH 7.5. Apolipoprotein E (apoE), a representative amyloid-associated protein, formed a stable complex with A beta 2M amyloid fibrils and inhibited the depolymerization of A beta 2M amyloid fibrils dose-dependently in a range of 0--10 microM. These results showed that apoE could enhance the deposition of amyloid fibrils in vivo, possibly by binding directly to the surface of the fibrils and stabilizing the conformation of beta 2-m in the fibrils.
β2-微球蛋白相关（Aβ2M）淀粉样变性是长期血液透析患者常见且严重的并发症，β2-微球蛋白（β2-m）是Aβ2M淀粉样纤维的主要结构成分。用硫黄素T进行的荧光光谱分析和电子显微镜研究表明，Aβ2M淀粉样纤维在中性至碱性pH条件下容易解聚为单体β2-m。圆二色性分析表明，在pH 7.5开始解聚反应后不久，Aβ2M淀粉样纤维中β2-m的特征光谱就会发生变化，类似于pH 7.5时单体β2-m的光谱。载脂蛋白E（apoE）是一种代表性的淀粉样相关蛋白，它与Aβ2M淀粉样纤维形成稳定的复合物，并在0-10μM范围内剂量依赖性地抑制Aβ2M淀粉样纤维的解聚。这些结果表明，apoE可能通过直接结合到纤维表面并稳定纤维中β2-m的构象，从而增强体内淀粉样纤维的沉积。
