Nichols A V, Blanche P J, Shore V G, Gong E L
Lawrence Berkeley Laboratory, University of California, Berkeley 94720.
Biochim Biophys Acta. 1989 Feb 20;1001(3):325-37. doi: 10.1016/0005-2760(89)90117-3.
Incubation studies were performed on plasma obtained from subjects selected for relatively low levels of high-density lipoprotein cholesterol (HDL-C) (no greater than 30 mg/dl) and particle size distributions enriched in the HDL3 subclass. Incubation (12 h, 37 degrees C) of plasma in the presence or absence of lecithin: cholesterol acyltransferase activity produces marked alteration in size profiles of both major apolipoprotein-specific HDL3 populations (HDL3(AI w AII), HDL3 species containing both apolipoprotein A-I and apolipoprotein A-II, and HDL3(AI w/o AII), HDL3 species containing apolipoprotein A-I) as isolated by immunoaffinity chromatography. In the presence or absence of lecithin: cholesterol acyltransferase activity, plasma incubation results in a shift of HDL3(AI w AII) species (initial mean sizes of major components, approx. 8.8 and 8.0 nm) predominantly to larger particles (mean size, 9.8 nm). A less prominent shift to smaller particles (mean size, 7.8 nm) accompanies the conversion to larger particles only when the enzyme is active. Combined shifts to larger (mean size, 9.8 nm) and smaller (mean size, 7.4 nm) particles are observed for HDL3(AI w/o AII) particles (mean size, 8.3 nm) also only in the presence of enzyme activity. However, in the absence of enzyme activity, HDL3(AI w/o AII) species, unlike the HDL3(AI w AII) species, are converted to smaller (mean size 7.4 nm) rather than to larger particles. Like native HDL2b(AI w/o AII) particles, the larger HDL3(AI w/o AII) conversion products exhibit a protein moiety with molecular weight equivalent to four apolipoprotein A-I molecules per particle; small HDL3(AI w/o AII) products are comprised predominantly of particles with two apolipoprotein A-I per particle. Incubation-induced conversion of HDL3 particles in the presence of lecithin: cholesterol acyltransferase activity is associated with increased binding of both apolipoprotein-specific HDL populations to low-density lipoproteins (LDL). The present studies indicate that, in the absence of lecithin: cholesterol acyltransferase activity, the two HDL3 populations follow different conversion pathways, possibly due to apolipoprotein-specific activities of lipid transfer protein or conversion protein in plasma. Our studies also suggest that lecithin: cholesterol acyltransferase activity may play a role in the origins of large HDL2b(AI w/o AII) species in human plasma by participating in the conversion of HDL3(AI w/o AII) particles, initially with three apolipoprotein A-I, to larger particles with four apolipoprotein A-I per particle.
对从高密度脂蛋白胆固醇（HDL-C）水平相对较低（不超过30mg/dl）且富含HDL3亚类颗粒大小分布的受试者获得的血浆进行孵育研究。在有或没有卵磷脂胆固醇酰基转移酶活性的情况下对血浆进行孵育（12小时，37摄氏度），会使通过免疫亲和色谱分离的两种主要载脂蛋白特异性HDL3群体（HDL3(AI伴AII)，含有载脂蛋白A-I和载脂蛋白A-II的HDL3种类，以及HDL3(AI不伴AII)，含有载脂蛋白A-I的HDL3种类）的大小分布产生显著变化。在有或没有卵磷脂胆固醇酰基转移酶活性的情况下，血浆孵育会导致HDL3(AI伴AII)种类（主要成分的初始平均大小约为8.8和8.0nm）主要向更大颗粒（平均大小9.8nm）转变。只有当酶有活性时，向更大颗粒转变的同时才会伴随向更小颗粒（平均大小7.8nm）的不太明显的转变。对于HDL3(AI不伴AII)颗粒（平均大小8.3nm），也只有在酶活性存在时才会观察到向更大颗粒（平均大小9.8nm）和更小颗粒（平均大小7.4nm）的联合转变。然而，在没有酶活性的情况下，与HDL3(AI伴AII)种类不同，HDL3(AI不伴AII)种类会转变为更小颗粒（平均大小7.4nm）而非更大颗粒。与天然HDL2b(AI不伴AII)颗粒一样，更大的HDL3(AI不伴AII)转化产物显示每个颗粒具有与四个载脂蛋白A-I分子分子量相当的蛋白质部分；小的HDL3(AI不伴AII)产物主要由每个颗粒含有两个载脂蛋白A-I的颗粒组成。在卵磷脂胆固醇酰基转移酶活性存在的情况下，孵育诱导的HDL3颗粒转化与两种载脂蛋白特异性HDL群体与低密度脂蛋白（LDL）结合增加有关。目前的研究表明，在没有卵磷脂胆固醇酰基转移酶活性的情况下，这两种HDL3群体遵循不同的转化途径，可能是由于血浆中脂质转运蛋白或转化蛋白的载脂蛋白特异性活性。我们的研究还表明，卵磷脂胆固醇酰基转移酶活性可能通过参与HDL3(AI不伴AII)颗粒（最初每个颗粒有三个载脂蛋白A-I）向每个颗粒有四个载脂蛋白A-I的更大颗粒的转化，在人血浆中大型HDL2b(AI不伴AII)种类的起源中发挥作用。
