Apolipoprotein AIV: A potent endogenous inhibitor of lipid oxidation
Apolipoprotein AIV: A potent endogenous inhibitor of lipid oxidation
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DOI：
10.1152/ajpheart.1998.274.5.h1836
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发表时间：
1998-05-01
影响因子：
4.8
通讯作者：
Tso, P
中科院分区：
文献类型：
--
作者：
Qin, XF;Swertfeger, DK;Tso, P
转基因小鼠中载脂蛋白AIV的过表达赋予apoE基因敲除动物显著的抗动脉粥样硬化保护作用，即使在存在更严重的致动脉粥样硬化脂质谱的情况下。由于脂蛋白氧化已被认为是动脉粥样硬化发展的关键，因此研究了apoAIV的抗氧化活性。空腹肠淋巴液用于模拟间质液中的条件，间质液是体内脂蛋白氧化的潜在部位。ApoAIV（10 μ g/ml）显著抑制铜介导的淋巴氧化。使用纯化的低密度脂蛋白进一步评价这种抑制作用。加入apoAIV（2.5 μ g/ml）使50%共轭二烯形成的时间增加了2.4倍，而apoE或BSA即使在20 μ g/ml时也没有显示出这种保护作用。在繁殖阶段添加apoAIV也导致剂量依赖性抑制。ApoAIV还保护巨噬细胞诱导的禁食淋巴氧化。这些结果首次证明了apoAIV是一种有效的内源性抗氧化剂。
Overexpression of apolipoprotein (apo) AIV in transgenic mice confers significant protection against atherosclerosis in apoE knockout animals even in the presence of a more severe atherogenic lipid profile. Because lipoprotein oxidation has been recognized to be pivotal in development of atherosclerosis, the antioxidative activity of apoAIV was investigated. Fasting intestinal lymph was used to mimic conditions in the interstitial fluid, the potential site for lipoprotein oxidation in vivo. ApoAIV (10 mu g/ml) significantly inhibited copper-mediated oxidation of lymph. This inhibitory effect was further evaluated using purified low-density Lipoprotein. Addition of apoAIV (2.5 mu g/ml) increased the time of 50% conjugated diene formation by 2.4-fold, whereas apoE or BSA did not show such a protection even at 20 mu g/ml. Addition of apoAIV during the propagation phase also resulted in a dose-dependent inhibition. ApoAIV also protected macrophage-induced oxidation of fasting lymph. These results provide the first evidence that apoAIV is a potent endogenous antioxidant.