HIGH-DENSITY-LIPOPROTEIN IS THE MAJOR CARRIER OF LIPID HYDROPEROXIDES IN HUMAN BLOOD-PLASMA FROM FASTING DONORS
HIGH-DENSITY-LIPOPROTEIN IS THE MAJOR CARRIER OF LIPID HYDROPEROXIDES IN HUMAN BLOOD-PLASMA FROM FASTING DONORS
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DOI：
10.1073/pnas.89.21.10316
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发表时间：
1992-11-01
影响因子：
11.1
通讯作者：
STOCKER, R
中科院分区：
文献类型：
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作者：
BOWRY, VW;STANLEY, KK;STOCKER, R
对健康、空腹供者未经处理的新鲜血浆的分析显示，高密度脂蛋白（HDL）颗粒携带大多数（几乎等于85%）可检测的氧化核心脂蛋白脂。低密度脂蛋白（LDL）脂质相对不含过氧化物。在体外实验中，空腹供体经凝胶过滤后的血浆在低、稳定的过氧自由基流量下的轻度氧化，最初会导致高密度脂蛋白优先氧化，而不是低密度脂蛋白，直到低密度脂蛋白中存在的大部分泛醇-10被消耗。此后，LDL核心脂质被更快地氧化。分离的脂蛋白也有类似的表现。脂质氢过氧化物在HDL中的优先积累反映了与LDL相比，大多数HDL颗粒缺乏抗氧化剂，LDL每颗粒含有8-12 α -生育酚和0.5-1.0泛醇-10分子。当将HDL和LDL中的胆固醇酯氢过氧化物（CEOOHs）添加到37℃的新鲜血浆中长达20小时时，它们是稳定的。CEOOHs从HDL到LDL的转移速度太慢，不足以影响体外血浆氧化数据。将轻度氧化的LDL和HDL与培养的肝细胞孵育后，LDL中的CEOOHs呈线性去除（1小时内损失40%），而HDL则呈先快后慢的双相去除。我们的数据表明HDL是循环血浆脂质氢过氧化物的主要载体，并且表明HDL脂质在体内可能比LDL中的脂质更快地被氧化。HDL中CEOOHs在肝脏中的快速清除可能意味着HDL通过减少LDL中氧化脂质的积累可能具有有益作用。
Analysis of untreated fresh blood plasma from healthy, fasting donors revealed that high density lipoprotein (HDL) particles carry most (almost-equal-to 85%) of the detectable oxidized core lipoprotein lipids. Low density lipoprotein (LDL) lipids are relatively peroxide-free. In vitro the mild oxidation of gel-filtered plasma from fasting donors with a low, steady flux of aqueous peroxyl radicals initially caused preferential oxidation of HDL rather than LDL lipids until most ubiquinol-10 present in LDL was consumed. Thereafter, LDL core lipids were oxidized more rapidly. Isolated lipoproteins behaved similarly. Preferential accumulation of lipid hydroperoxides in HDL reflects the lack of antioxidants in most HDL particles compared to LDL, which contained 8-12 alpha-tocopherol and 0.5-1.0 ubiquinol-10 molecules per particle. Cholesteryl ester hydroperoxides (CEOOHs) in HDL and LDL were stable when added to fresh plasma at 37-degrees-C for up to 20 hr. Transfer of CEOOHs from HDL to LDL was too slow to have influenced the in vitro plasma oxidation data. Incubation of mildly oxidized LDL and HDL with cultured hepatocytes afforded a linear removal of CEOOHs from LDL (40% loss over 1 hr), whereas a fast-then-slow biphasic removal was observed for HDL. Our data show that HDL is the principal vehicle for circulating plasma lipid hydroperoxides and suggest that HDL lipids may be more rapidly oxidized than those in LDL in vivo. The rapid hepatic clearance of CEOOHs in HDL could imply a possible beneficial role of HDL by attenuating the build-up of oxidized lipids in LDL.