Miyata T, Taneda S, Kawai R, Ueda Y, Horiuchi S, Hara M, Maeda K, Monnier V M
Department of Internal Medicine, Branch Hospital, Nagoya University School of Medicine, Japan.
Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2353-8. doi: 10.1073/pnas.93.6.2353.
beta-2-Microglobulin (beta-2m) is a major constituent of amyloid fibrils in patients with dialysis-related amyloidosis (DRA). Recently, we found that the pigmented and fluorescent adducts formed nonenzymatically between sugar and protein, known as advanced glycation end products (AGEs), were present in beta-2m-containing amyloid fibrils, suggesting the possible involvement of AGE-modified beta-2m in bone and joint destruction in DRA. As an extension of our search for the native structure of AGEs in beta-2m of patients with DRA, the present study focused on pentosidine, a fluorescent cross-linked glycoxidation product. Determination by both HPLC assay and competitive ELISA demonstrated a significant amount of pentosidine in amyloid-fibril beta-2m from long-term hemodialysis patients with DRA, and the acidic isoform of beta-2m in the serum and urine of hemodialysis patients. A further immunohistochemical study revealed the positive immunostaining for pentosidine and immunoreactive AGEs and beta-2m in macrophage-infiltrated amyloid deposits of long-term hemodialysis patients with DRA. These findings implicate a potential link of glycoxidation products in long-lived beta-2m-containing amyloid fibrils to the pathogenesis of DRA.
β2-微球蛋白（β2m）是透析相关性淀粉样变（DRA）患者淀粉样纤维的主要成分。最近，我们发现糖与蛋白质非酶促形成的色素沉着和荧光加合物，即晚期糖基化终产物（AGEs），存在于含β2m的淀粉样纤维中，这表明AGE修饰的β2m可能参与了DRA患者的骨骼和关节破坏。作为我们对DRA患者β2m中AGEs天然结构研究的延伸，本研究聚焦于戊糖苷，一种荧光交联糖氧化产物。通过高效液相色谱分析和竞争性酶联免疫吸附测定法测定表明，长期透析的DRA患者的淀粉样纤维β2m中存在大量戊糖苷，并且在血液透析患者的血清和尿液中存在β2m的酸性异构体。进一步的免疫组织化学研究显示，长期透析的DRA患者巨噬细胞浸润的淀粉样沉积物中戊糖苷、免疫反应性AGEs和β2m呈阳性免疫染色。这些发现表明，含β2m的长寿淀粉样纤维中的糖氧化产物与DRA的发病机制之间存在潜在联系。
