Sialic acid moiety of apolipoprotein E3 at Thr194 affects its interaction with β-amyloid1–42 peptides
Sialic acid moiety of apolipoprotein E3 at Thr194 affects its interaction with β-amyloid1–42 peptides
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DOI：
10.1016/j.cca.2007.10.024
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发表时间：
2008-02
影响因子：
5
通讯作者：
M. Sugano;K. Yamauchi;Kenji Kawasaki;M. Tozuka;K. Fujita;N. Okumura;H. Ota
中科院分区：
文献类型：
--
作者：
M. Sugano;K. Yamauchi;Kenji Kawasaki;M. Tozuka;K. Fujita;N. Okumura;H. Ota
研究背景载脂蛋白E（apo E）和β-淀粉样蛋白（Aβ）之间的相互作用与阿尔茨海默病（AD）的发生有关，但其具体机制尚不清楚。脑脊液中的ApoE被广泛唾液酸化，并且已知某些蛋白质的唾液酸化调节生物学功能。方法制备正常apoE 3及其突变体（Thr 194 → Ala），采用表面等离子体共振（SPR）技术分析apoE 3与Aβ1- 42的相互作用。此外，我们使用神经氨酸酶处理的含apoE的脂蛋白进行SPR测定。我们还评估了突变体对apoE 3与脂质体相互作用的影响。突变体apoE 3 #的结合亲合力约为正常apoE 3的50%（p<0.0001）。神经氨酸酶处理后，含apoE的脂蛋白对Aβ1- 42的结合亲和力降低。结论：我们认为AD的发生不仅受apoE亚型的控制，而且受apoE翻译后修饰的控制，如唾液酸部分的修饰，这些修饰在apoE中是丰富的。
BACKGROUNDThe interaction between apolipoprotein (apo) E and β-amyloid (Aβ) is associated with the development of Alzheimer's disease (AD); however, the details remain unknown. ApoE in cerebrospinal fluid is extensively sialylated, and sialylation of certain proteins are known to modulate biological function. We investigated the effects of a sialic acid moiety of apoE on the apoE–Aβ interaction.METHODSWe prepared normal apoE3 and its mutant (Thr194→ Ala) and analyzed their interactions with Aβ1–42by using the surface plasmon resonance (SPR) assay. In addition, we performed the SPR assay by using apoE-containing lipoproteins treated with neuraminidase. We also assessed the effect of the mutation on the interaction of apoE3 with liposomes.RESULTSThe binding avidity of the mutant apoE3#was approximately 50% that of normal apoE3 (p<0.0001). The binding avidity of the apoE-containing lipoproteins for Aβ1–42reduced after neuraminidase treatment.CONCLUSIONSWe suggest that AD development is controlled not only by the apoE isoforms but also by the posttranslational modifications in apoE, such as those in the sialic acid moieties, which are abundant in apoE derived from the brain.