Virgolini I, Li S R, Lupattelli G, Pidlich J, Angelberger P, Banyai M, Sinzinger H
Atherosclerosis Research Group (ASF), Vienna, Austria.
Prostaglandins. 1991 Jul;42(1):81-93. doi: 10.1016/0090-6980(91)90096-x.
The effect of PGE1 on low density lipoprotein (LDL) apo-B-receptor binding was examined in human, rat and swine liver. Autologous LDL (for humans and swines) and homologous LDL (for rats) were isolated by ultracentrifugation and labelled with 123I using Iodogen followed by purification with dialysis. LDL-concentrations of 0.1-6 micrograms protein/ml were used for direct binding assays investigating the specific binding of labelled LDL in presence of increasing PGE1-concentrations (100 pM to 100 microM). In separate experiments the effect of PGE1 on displacement of specifically bound 123I-LDL by unlabelled ones was studied. The binding capacities estimated by Scatchard analysis were similar for human and rat liver LDL-apo-B-receptor binding, however, swine liver exhibited a significantly (p less than 0.001) lower binding capacity for 123I-LDL. PGE1 significantly (p less than 0.01-0.001) increased the amount of 123I-LDL specifically bound to the liver apo-B-receptors and the binding affinity in all liver preparations of the 3 species in a dose-dependent manner. PGE1 also significantly increased competition of unlabelled LDL for 123I-LDL bound to its specific apo-B-receptors in a dose-dependent manner (p less than 0.01-0.001) with an ED50 of 123 +/- 64 nM for human liver, 901 +/- 102 nM for rat liver obtained during anaesthesia, 74 +/- 23 nM for rat liver obtained after decapitation and 941 +/- 121 nM for swine liver. In human liver iloprost (ED50 = 876 +/- 53 nM) and PGI2 (ED50 = 52 +/- 12 microM) were less effective than PGE1, PGE2 had no effect on LDL-induced competition. It is concluded that PGE1 renders LDL more sensitive for apo-B-receptor binding suggesting a potential hypolipidemic action of PGE1.
研究了前列腺素E1（PGE1）对人、大鼠和猪肝中低密度脂蛋白（LDL）载脂蛋白B受体结合的影响。通过超速离心分离自体LDL（用于人和猪）和同源LDL（用于大鼠），使用碘昔芬将其用123I标记，然后通过透析进行纯化。使用0.1 - 6微克蛋白质/毫升的LDL浓度进行直接结合测定，以研究在PGE1浓度增加（100皮摩尔至100微摩尔）时标记LDL的特异性结合。在单独的实验中，研究了PGE1对未标记LDL取代特异性结合的123I - LDL的影响。通过Scatchard分析估计的结合能力，人肝和大鼠肝LDL载脂蛋白B受体结合相似，然而，猪肝对123I - LDL的结合能力显著（p < 0.001）较低。PGE1以剂量依赖性方式显著（p < 0.01 - 0.001）增加了特异性结合到肝载脂蛋白B受体的123I - LDL的量以及在所有3种动物肝脏制剂中的结合亲和力。PGE1还以剂量依赖性方式显著增加了未标记LDL对与其特异性载脂蛋白B受体结合的123I - LDL的竞争（p < 0.01 - 0.001），人肝的半数有效浓度（ED50）为123 ± 64纳摩尔，麻醉状态下大鼠肝为901 ± 102纳摩尔，断头后大鼠肝为74 ± 23纳摩尔，猪肝为941 ± 121纳摩尔。在人肝中，伊洛前列素（ED50 = 876 ± 53纳摩尔）和前列环素（PGI2，ED50 = 52 ± 12微摩尔）比PGE1效果差，PGE2对LDL诱导的竞争无影响。结论是PGE1使LDL对载脂蛋白B受体结合更敏感，提示PGE1具有潜在的降血脂作用。
