Identification of pentosidine as a native structure for advanced glycation end products in beta(2)-microglobulin-containing amyloid fibrils in patients with dialysis-related amyloidosis
Identification of pentosidine as a native structure for advanced glycation end products in beta(2)-microglobulin-containing amyloid fibrils in patients with dialysis-related amyloidosis
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DOI：
10.1073/pnas.93.6.2353
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发表时间：
1996-03-19
影响因子：
11.1
通讯作者：
Monnier, VM
中科院分区：
文献类型：
--
作者：
Miyata, T;Taneda, S;Monnier, VM
β(2)-微球蛋白（β (2)m）是透析相关性淀粉样变性（DRA）患者淀粉样原纤维的主要成分。最近，我们发现含有β (2)m的淀粉样原纤维中存在以非酶方式在糖和蛋白质之间形成的色素和荧光加合物，即晚期糖基化终产物（AGEs），这表明age修饰的β (2)m可能参与了DRA的骨和关节破坏。作为我们对DRA患者β (2)m中AGEs天然结构研究的延伸，本研究将重点放在了荧光交联糖氧化产物戊苷上。高效液相色谱法和竞争性酶联免疫吸附试验均表明，长期血液透析患者的淀粉样纤维β (2)m中存在大量戊苷，血液透析患者的血清和尿液中存在β (2)m的酸性异构体。进一步的免疫组织化学研究显示，长期血液透析患者巨噬细胞浸润的淀粉样蛋白沉积物中戊苷、免疫反应性AGEs和β (2)m的免疫染色呈阳性。这些发现暗示了长寿命的含有β (2)m的淀粉样蛋白原纤维中的糖氧化产物与DRA发病机制的潜在联系。
beta(2)-Microglobulin (beta(2)m) 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(2)m-containing amyloid fibrils, suggesting the possible involvement of AGE-modified beta(2)m in bone and joint destruction in DRA, As an extension of our search for the native structure of AGEs in beta(2)m 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(2)m from longterm hemodialysis patients with DRA, and the acidic isoform of beta(2)m in the serum and urine of hemodialysis patients. A further immunohistochemical study revealed the positive immunostaining for pentosidine and immunoreactive AGEs and beta(2)m in macrophage-infiltrated amyloid deposits of long-term hemodialysis patients,vith DRA. These findings implicate a potential link of glycoxidation products in long-lived beta(2)m-containing amyloid fibrils to the pathogenesis of DRA.