Jolivalt C, Leininger-Muller B, Bertrand P, Herber R, Christen Y, Siest G
Centre du Médicament, UPRES, Faculté de Pharmacie, Université Henri Poincaré Nancy 1, France.
Free Radic Biol Med. 2000 Jan 1;28(1):129-40. doi: 10.1016/s0891-5849(99)00232-4.
Accumulation of oxidized proteins has been demonstrated in the brain of patients suffering from Alzheimer's disease (AD). Among the proteins found in cerebral amyloid deposits, apolipoprotein (apo) E is a polymorphic protein which one specific isoform, apo E4, has been widely associated with AD. Apo E may be linked with AD by its isoform-specific interaction with lipids or other proteins in amyloid plaques. Using the myeloperoxidase oxidative system, we report that oxidation of the three recombinant apo E isoforms is differential (as estimated using immunoblot and high-performance liquid chromatography analysis), with apo E4 being more susceptible than apo E3, which in turn is much more susceptible than apo E2. In addition, susceptibility to thrombin proteolysis is reduced when apo E is oxidized, and oxidation of apo E decreases its incorporation into phospholipid discs by approximately 50%. Oxidation of apo E may contribute to inefficient lipid recycling in the brain, particularly regarding apo E4 and E3. Our results link and strengthen both the E4 allele linkage with AD and the role of protein oxidation in AD. The cerebral mechanisms underlying apo E oxidation and/or myeloperoxidase functions in vivo remain to be assessed.
在阿尔茨海默病（AD）患者的大脑中已证实存在氧化蛋白质的积累。在脑淀粉样沉积物中发现的蛋白质中，载脂蛋白（apo）E是一种多态性蛋白质，其中一种特定异构体apo E4与AD广泛相关。Apo E可能通过其异构体与淀粉样斑块中的脂质或其他蛋白质的特异性相互作用与AD相关联。利用髓过氧化物酶氧化系统，我们报告三种重组apo E异构体的氧化是不同的（如通过免疫印迹和高效液相色谱分析估计），apo E4比apo E3更易氧化，而apo E3又比apo E2更易氧化。此外，当apo E被氧化时，其对凝血酶蛋白水解的敏感性降低，并且apo E的氧化使其掺入磷脂盘的量减少约50%。Apo E的氧化可能导致大脑中脂质循环效率低下，特别是对于apo E4和E3而言。我们的结果将E4等位基因与AD的联系以及蛋白质氧化在AD中的作用联系起来并加强了。Apo E氧化和/或髓过氧化物酶在体内功能的脑机制仍有待评估。
