Niwa T, Katsuzaki T, Miyazaki S, Momoi T, Akiba T, Miyazaki T, Nokura K, Hayase F, Tatemichi N, Takei Y
Nagoya University Branch Hospital, Japan.
Kidney Int. 1997 Jan;51(1):187-94. doi: 10.1038/ki.1997.23.
We have recently demonstrated by immunohistochemistry that amyloid beta 2-microglobulin (beta 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 beta 2m-positive amyloid deposits in these patients. Western blotting using the antibody demonstrated that beta 2m extracted from the synovium amyloid of hemodialysis patients was modified with imidazolone. Further, beta 2m isolated from the blood ultrafiltrate of hemodialyzed patients was also modified with imidazolone. In vitro incubation of beta 2m with 3-DG produced imidazolone-modified beta 2m. In conclusion, amyloid tissue beta2m is modified with imidazolone in patients with DRA. 3-DG accumulating in uremic serum may be involved in the modification of beta 2m with imidazolone.
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（DRA）中，β2微球蛋白（β2m）被晚期糖基化终产物（AGEs）修饰。为了进一步研究美拉德反应在DRA发病机制中的作用，我们制备了一种针对咪唑啉酮的单克隆抗体，咪唑啉酮是一种新型AGE，是精氨酸与3-脱氧葡萄糖酮（3-DG）的反应产物，在尿毒症血清中蓄积。然后我们使用该抗体通过免疫组织化学确定了咪唑啉酮在淀粉样组织中的定位。从6例腕管综合征患者和2例破坏性脊椎关节病患者获取腕管和黄韧带的结缔组织。咪唑啉酮定位于这些患者所有β2m阳性淀粉样沉积物中。使用该抗体进行的蛋白质印迹表明，从血液透析患者滑膜淀粉样物质中提取的β2m被咪唑啉酮修饰。此外，从血液透析患者的血液超滤物中分离出的β2m也被咪唑啉酮修饰。β2m与3-DG的体外孵育产生了咪唑啉酮修饰的β2m。总之，DRA患者的淀粉样组织β2m被咪唑啉酮修饰。尿毒症血清中蓄积的3-DG可能参与β2m的咪唑啉酮修饰。
