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首页> 外文期刊>Kidney international. >Amyloid |[beta]|2-microglobulin is modified with imidazolone, a novel advanced glycation end product, in dialysis-related amyloidosis
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Amyloid |[beta]|2-microglobulin is modified with imidazolone, a novel advanced glycation end product, in dialysis-related amyloidosis

机译:在透析相关的淀粉样变性病中,用新型先进的糖基化终产物咪唑啉酮修饰了淀粉样蛋白|β| 2-微球蛋白

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Amyloid 2-microglobulin is modified with imidazolone, a novel advanced glycation end product, in dialysis-related amyloidosis. We have recently demonstrated by immunohistochemistry that amyloid 2-microglobulin (2m) is modified with advanced glycation end products (AGEs) in dialysis-related amyloidosis (DRA). To further investigate the role of the Maillard reaction in the pathogenesis of DRA, we produced a monoclonal antibody to imidazolone, a novel AGE, and a reaction product of arginine and 3-deoxyglucosone (3-DG) which was accumulated in uremic serum. Then we determined the localization of imidazolone in the amyloid tissues by immunohistochemistry using the antibody. The connective tissues in carpal tunnel and ligamentum flavum were obtained from six patients with carpal tunnel syndrome and two patients with destructive spondyloarthropathy. Imidazolone was localized to all the 2m-positive amyloid deposits in these patients. Western blotting using the antibody demonstrated that 2m extracted from the synovium amyloid of hemodialysis patients was modified with imidazolone. Further, 2m isolated from the blood ultrafiltrate of hemodialyzed patients was also modified with imidazolone. In vitro incubation of 2m with 3-DG produced imidazolone-modified 2m. In conclusion, amyloid tissue 2m is modified with imidazolone in patients with DRA. 3-DG accumulating in uremic serum may be involved in the modification of 2m with imidazolone.
机译:在透析相关的淀粉样变性病中,用新型先进的糖基化终产物咪唑啉酮修饰了2-淀粉样蛋白微球蛋白。我们最近通过免疫组织化学证明,在透析相关性淀粉样变性病(DRA)中,淀粉样2-微球蛋白(2m)被高级糖基化终产物(AGEs)修饰。为了进一步研究美拉德反应在DRA发病机理中的作用,我们生产了一种抗咪唑酮的单克隆抗体,一种新的AGE以及精氨酸和3-脱氧葡萄糖苷(3-DG)的反应产物,该产物积聚在尿毒症血清中。然后,我们使用该抗体通过免疫组织化学确定了咪唑酮在淀粉样蛋白组织中的定位。腕管综合征和黄韧带的结缔组织取自6例腕管综合征患者和2例破坏性脊柱关节炎患者。咪唑酮定位于这些患者中所有2m阳性淀粉样蛋白沉积物。使用该抗体的蛋白质印迹表明,从血液透析患者的滑膜淀粉样蛋白中提取的2m被咪唑酮修饰。此外,从咪唑啉酮修饰从血液透析患者的血液超滤物中分离的2m。用3-DG在2m的体外温育产生了咪唑酮修饰的2m。总之,DRA患者的咪唑酮可修饰2m淀粉样组织。尿毒症血清中积累的3-DG可能参与了咪唑酮对2m的修饰。

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