College of Bioengineering, Key Laboratory of Bio-organic Chemistry, Dalian University, 10-Xuefu Avenue, Dalian Economical and Technological Development Zone, Liaoning 116622, China.
J Biochem. 2011 Jan;149(1):35-42. doi: 10.1093/jb/mvq111. Epub 2010 Sep 27.
Our prior study has been reported the formation of the oxidized low-density lipoprotein (oxLDL)/β(2)-glycoproteinI (β(2)-GPI)/autoantibody complex facilitated the antiphospholipid syndrome (APS) process. The domain V of β(2)-GPI binds to the negatively charged molecules, e.g. 7-ketochoresteryl-9-caboxynonanoate (oxLig-1) derived from the oxLDL and mediates the interaction between oxLDL and β(2)-GPI. In the present study, the oxLig-1/β(2)-GPI/anti-β(2)-GPI Ab (WB-CAL-1) model was established. The recombinant domain V of β(2)-GPI (rβ(2)-GPI DV) expressed in Escherichia coli competitively inhibits the interaction between β(2)-GPI and oxLig-1 in the enzyme-linked immunoassay. Moreover, the rβ(2)-GPI DV significantly inhibits the formation of the oxLig-1/β(2)-GPI/autoantibody complex in an APS patient. The present work suggests a novel possibility that rβ(2)-GPI DV could be used to inhibit the formation of oxLDL/β(2)-GPI/autoantibody complex, and give us a hint for the development of new therapeutic strategies to prevent the APS process.
我们之前的研究已经报道了氧化型低密度脂蛋白（oxLDL）/β(2)-糖蛋白 I（β(2)-GPI）/自身抗体复合物的形成促进了抗磷脂综合征（APS）的发生。β(2)-GPI 的结构域 V 与带负电荷的分子结合，例如 oxLDL 衍生的 7-酮胆固醇-9-羧基壬酸酯（oxLig-1），并介导 oxLDL 与 β(2)-GPI 之间的相互作用。在本研究中，建立了 oxLig-1/β(2)-GPI/抗-β(2)-GPI Ab（WB-CAL-1）模型。在大肠埃希菌中表达的重组 β(2)-GPI 结构域 V（rβ(2)-GPI DV）在酶联免疫吸附试验中竞争性抑制了 β(2)-GPI 与 oxLig-1 的相互作用。此外，rβ(2)-GPI DV 显著抑制了 APS 患者中 oxLig-1/β(2)-GPI/自身抗体复合物的形成。本研究提示了 rβ(2)-GPI DV 可能用于抑制 oxLDL/β(2)-GPI/自身抗体复合物的形成，为开发新的治疗策略以预防 APS 提供了思路。
