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Capillary Electrophoretic Profile of β 2-Microglobulin Intermediate Associated With Hemodialysis

机译:血液透析相关的β2-微球蛋白中间体的毛细管电泳图谱

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摘要

We previously identified an intermediate β 2-microglobulin (I-β 2m), which is an amyloidogenic β 2m variant, via capillary electrophoresis (CE) and reported hemodialysis (HD)-associated variations in the serum concentrations of each β 2m component, including that found in the rebound phase. Recent research has indicated that I-β 2m can bind, via the SO 3 - moiety, with glycosaminoglycan or proteoglycan, which are major components of interstitial tissue. Because alterations in I-β 2m are likely to be important in view of the possible accumulation of amyloidogenic precursor proteins in the interstitial space, we studied the I-β 2m profile as related to HD. We used CE to determine the I-β 2m profile both at the start and at the end of HD and during the rebound phase in 12 HD patients. We found both an unfolded β 2m and a destructured I-β 2m. More important, two peaks appeared in the rebound phase, one suggesting a refolding and one suggesting an irreversible destruction. Given that the intercompartmental transfer coefficient for β 2m is 1.0, our results indicated concomitant processes occurring after HD: refolding of the β 2m conformation and trapping of destructured I-β 2m in the extravascular space. Because the trapping of destructured I-β 2m supposedly leads to accumulation of β 2m in the interstitial space, we have proposed a new concept-a "shuttle" concept-for amyloid formation from β 2m in the HD setting.
机译:我们之前通过毛细管电泳(CE)鉴定了一个中间β2微球蛋白(I-β2m),它是淀粉样蛋白生成的β2m变体,并报告了与血液透析(HD)相关的每种β2m组分的血清浓度变化,包括在反弹阶段发现。最近的研究表明,I-β2m可通过SO 3-部分与糖胺聚糖或蛋白聚糖结合,后者是间质组织的主要成分。由于淀粉样蛋白前体蛋白可能在间隙中积累,因此I-β2m的改变可能很重要,因此我们研究了与HD相关的I-β2m分布。我们使用CE来确定12例HD患者在HD开始和结束时以及反弹阶段期间的I-β2m分布。我们发现未折叠的β2m和变形的I-β2m。更重要的是,在反弹阶段出现了两个峰,一个峰表明发生了折叠,另一个峰表明了不可逆的破坏。考虑到β2m的室间转移系数为1.0,我们的结果表明HD后发生伴随的过程:β2m构象的重折叠和变性的I-β2m在血管外空间的捕获。因为据推测,捕获变形的I-β2m会导致β2m在空隙空间中积聚,所以我们提出了一个新概念-“穿梭”概念-在HD环境中由β2m形成淀粉样蛋白。

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