Novel action of apolipoprotein E (ApoE): ApoE isoform specifically inhibits lipid-particle-mediated cholesterol release from neurons.
Novel action of apolipoprotein E (ApoE): ApoE isoform specifically inhibits lipid-particle-mediated cholesterol release from neurons.
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DOI：
10.1186/1750-1326-2-9
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发表时间：
2007-05-15
影响因子：
15.1
通讯作者：
Michikawa M
中科院分区：
文献类型：
--
作者：
Gong JS;Morita SY;Kobayashi M;Handa T;Fujita SC;Yanagisawa K;Michikawa M
由于脑脊液中的载脂蛋白E（apoE）大多与高密度脂蛋白（HDL）有关，因此，在中枢神经系统胆固醇代谢中，apoE-HDL复合物的作用应比游离apoE的作用更重要。然而，载脂蛋白E-HDL对胆固醇转运的载脂蛋白E亚型特异性作用仍不清楚。在这里，我们表明，apoE 3-HDL诱导显着的胆固醇从神经元释放，而apoE 4-HDL诱导很少。为了阐明这一现象的机制，我们使用了复合物的脂肪乳剂（EM）与重组apoE 3或apoE 4（apoE-EM）在不同的apoE浓度。当少数apoE分子与EM结合时，apoE 3-和apoE 4-EM诱导了显著的胆固醇释放，其水平与单独EM诱导的水平相似。当apoE与EM共同孵育时，apoE 3-EM诱导胆固醇释放，而apoE 4-EM诱导胆固醇释放的作用很小。在这些条件下，与EM结合的apoE 4分子数量多于apoE 3分子。当越来越多的apoE分子与EM结合时，apoE 3-EM和apoE 4-EM都几乎不诱导胆固醇释放。用β-巯基乙醇预孵育增加了与EM结合的apoE 3分子的数量，与apoE 4分子的数量相似，表明分子间二硫键形成的存在（apoE 3）或不存在（apoE 4）是导致更多apoE 4分子与EM结合的原因。这些结果表明，虽然apoE和脂质颗粒是脂质受体，但当apoE和脂质颗粒形成复合物时，颗粒表面上的apoE以apoE浓度依赖性方式抑制脂质颗粒介导的胆固醇从细胞释放。
Since the majority of apolipoprotein E (apoE) existing in the cerebrospinal fluid is associated with high-density lipoprotein (HDL), one should focus on the role of the apoE-HDL complex rather than on that of free apoE in cholesterol metabolism in the central nervous system. However, the apoE-isoform-specific effect of apoE-HDL on cholesterol transport remains unclarified. Here we show that apoE3-HDL induced a marked cholesterol release from neurons, while apoE4-HDL induced little. To elucidate the mechanism underlying this phenomenon, we used a complex of lipid emulsion (EM) with recombinant apoE3 or apoE4 (apoE-EM) at various apoE concentrations. When a small number of apoE molecules were associated with EM, apoE3- and apoE4-EM, induced a marked cholesterol release to a level similar to that induced by EM alone. However, when apoE at given concentrations was incubated with EM, apoE3-EM induced a marked cholesterol release, while apoE4-EM induced little. Under these conditions, a greater number of apoE4 molecules were associated with EM than apoE3 molecules. When an increasing number of apoE molecules were associated with EM, both apoE3-EM and apoE4-EM induced little cholesterol release. Preincubation with β-mercaptoethanol increased the number of apoE3 molecules associated with EM similar to that of apoE4 molecules, indicating that the presence (apoE3) or absence (apoE4) of intermolecular disulfide bond formation is responsible for the association of a greater number of apoE4 molecules to EM than apoE3 molecules. These results suggest that although apoE and a lipid particle are lipid acceptors, when apoE and a lipid particle form a complex, apoE on the particle surface inhibits the lipid particle-mediated cholesterol release from cells in an apoE-concentration-dependent manner.
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影响因子：
4.8
作者：
Saito, H;Dhanasekaran, P;Lund-Katz, S
通讯作者：
Lund-Katz, S
DOI：
10.1016/0005-2760(95)00165-4
发表时间：
1995-12-07
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM
影响因子：
--
作者：
Li, QQ;Czarnecka, H;Yokoyama, S
通讯作者：
Yokoyama, S
DOI：
10.1073/pnas.201279298
发表时间：
2001-09-25
影响因子：
11.1
作者：
Raffaï, RL;Dong, LM;Weisgraber, KH
通讯作者：
Weisgraber, KH
DOI：
10.1007/s11357-001-0001-9
发表时间：
2001-01-01
期刊：
JOURNAL OF THE AMERICAN AGING ASSOCIATION
影响因子：
--
作者：
Fan, QW;Iosbe, I;Michikawa, M
通讯作者：
Michikawa, M
影响因子：
4.7
作者：
Ito, J;Zhang, LY;Yokoyama, S
通讯作者：
Yokoyama, S