Bowry V W, Stanley K K, Stocker R
Biochemistry Group, Heart Research Institute, Sydney N.S.W., Australia.
Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10316-20. doi: 10.1073/pnas.89.21.10316.
Analysis of untreated fresh blood plasma from healthy, fasting donors revealed that high density lipoprotein (HDL) particles carry most (approximately 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.
对健康空腹献血者未经处理的新鲜血浆进行分析发现，高密度脂蛋白（HDL）颗粒携带了大部分（约85%）可检测到的氧化核心脂蛋白脂质。低密度脂蛋白（LDL）脂质相对无过氧化物。在体外，用低通量、稳定的水相过氧自由基对空腹献血者经凝胶过滤的血浆进行温和氧化，最初会优先氧化HDL而非LDL脂质，直到LDL中存在的大多数泛醇-10被消耗。此后，LDL核心脂质被更快地氧化。分离的脂蛋白表现类似。HDL中脂质氢过氧化物的优先积累反映出与LDL相比，大多数HDL颗粒中缺乏抗氧化剂，LDL每个颗粒含有8 - 12个α-生育酚分子和0.5 - 1.0个泛醇-10分子。当在37℃下添加到新鲜血浆中长达20小时时，HDL和LDL中的胆固醇酯氢过氧化物（CEOOHs）是稳定的。CEOOHs从HDL转移到LDL的速度太慢，无法影响体外血浆氧化数据。将轻度氧化的LDL和HDL与培养的肝细胞一起孵育，可使LDL中的CEOOHs呈线性去除（1小时内损失40%），而HDL则观察到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，并表明HDL脂质在体内可能比LDL脂质氧化得更快。HDL中CEOOHs的快速肝脏清除可能意味着HDL通过减少LDL中氧化脂质的积累而具有潜在的有益作用。
