Altered hepatic catabolism of low-density lipoprotein subjected to lipid peroxidation in vitro.
Altered hepatic catabolism of low-density lipoprotein subjected to lipid peroxidation in vitro.
复制标题
体外脂质过氧化作用改变了低密度脂蛋白的肝脏分解代谢。
DOI：
10.1042/bj2970573
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Wilcox,HG
中科院分区：
文献类型：
--
作者：
Stone,WL;Heimberg,M;Scott,RL;LeClair,I;Wilcox,HG
最近的证据表明，氧化修饰形式的低密度脂蛋白（LDL）可能是特别致动脉粥样硬化。本研究采用大鼠肝循环灌流系统，研究了脂质过氧化修饰的人低密度脂蛋白（LDL）的体外催化作用。一种双标记技术，允许本地LDL和修饰LDL同时在肝脏灌注系统进行研究。发现天然人LDL具有1.00 +/-0.21%/h的部分分解代谢率（FCR），与其他研究者一致。在30 μ M FeEDTA存在下氧化LDL 12小时并不显著影响其FCR。然而，在存在30 μ M FeEDTA的情况下，用超氧化物生成系统（黄嘌呤氧化酶、次黄嘌呤、O2）处理的LDL确实显示FCR显著增加（3.23 +/-0.19%/h）。天然LDL和氧化LDL与FeEDTA + O2的肝脏摄取量相似，但都显着低于超氧自由基产生系统处理的LDL的肝脏摄取。用胰酶水解LDL不影响其对氧化的敏感性或其FCR。LDL氧化导致α-生育酚而不是γ-生育酚的优先损失。这些数据表明，大鼠肝脏有效地分解代谢LDL氧化修饰的治疗与超氧化物生成系统。此外，我们的研究结果表明，只有非常低的血浆水平的高度氧化的低密度脂蛋白可以发现在体内的条件下。因此，肝脏可能在保护动脉血管系统免受高致动脉粥样硬化形式的LDL的影响方面发挥主要作用。
Recent evidence suggests that oxidatively modified forms of low-density lipoprotein (LDL) may be particularly atherogenic. In this investigation, the catabolism of human LDL modified by lipid peroxidation in vitro was studied with a recirculating rat liver perfusion system. A dual-labelling technique was used that permitted native LDL and modified LDL to be studied simultaneously in the liver perfusion system. Native human LDL was found to have a fractional catabolic rate (FCR) of 1.00 +/- 0.21%/h, in agreement with other investigators. Subjecting LDL to oxidation for 12 h in the presence of 30 microM FeEDTA did not significantly affect its FCR. LDL treated with a superoxide-generating system (xanthine oxidase, hypoxanthine, O2) in the presence of 30 microM FeEDTA did, however, show a significant increase in FCR (3.23 +/- 0.19%/h). The hepatic uptakes of native LDL and LDL oxidized with FeEDTA+O2 were similar, but both were significantly lower than the hepatic uptake of LDL treated with the superoxide-radical-generating system. The proteolysis of LDL with pancreatin did not influence either its susceptibility to oxidation or its FCR. LDL oxidation resulted in the preferential loss of alpha-tocopherol rather than gamma-tocopherol. These data indicate that the rat liver effectively catabolizes LDL oxidatively modified by treatment with the superoxide-generating system. Furthermore, our results suggest that only very low plasma levels of highly oxidized LDL could be found under conditions in vivo. The liver may therefore play a major role in protecting the arterial vasculature from highly atherogenic forms of LDL.