Bocharov A V, Huang W, Vishniakova T G, Zaitseva E V, Frolova E G, Rampal P, Bertolotti R
Cardiology Research Center, Moscow, Russia.
Metabolism. 1995 Jun;44(6):730-8. doi: 10.1016/0026-0495(95)90185-x.
Glucocorticoid hormones (GL) regulate high-density lipoprotein (HDL) plasma concentrations by increasing synthesis and secretion of HDL by the liver. However, little is known about the effect of GL on the uptake and processing of HDL by hepatocytes (HEP). To investigate this question, we studied the effects of dexamethasone (DEX) on the expression of high-affinity HDL-binding sites via the specific binding and internalization of iodine-labeled apolipoprotein E (apo E)-free HDL3 in a culture of rat HEP. Specific binding and internalization of HDL3 decreased by 60% in cells cultured in the absence of DEX for 48 hours. At concentrations of 10(-7) and 10(-5) mol/L, DEX prevented the decrease, maintaining specific binding and internalization versus the control level (at 24 hours). HDL-binding sites with a Kd of 20 micrograms/mL were revealed on the surface of cultured HEP. HEP demonstrated a greater binding capacity in the presence of DEX at concentrations of 10(-7) and 10(-5) mol/L (125 v 45 ng/mg cell protein). The effect of the hormone has demonstrated to be dose-dependent at concentrations between 10(-9) and 10(-7) mol/L, leveling off at 10(-7). Higher concentrations did not induce a further increase in specific binding and internalization. Withdrawal of the hormone from culture medium was associated with a decrease in specific binding of the ligand by 60% in the following 24 hours. To investigate the effect of glucocorticoid deficiency on liver uptake of HDL in vivo, specific binding and internalization were studied in a culture of HEP isolated from adrenalectomized rats (AER) at 2 hours after seeding.(ABSTRACT TRUNCATED AT 250 WORDS)
糖皮质激素（GL）通过增加肝脏中高密度脂蛋白（HDL）的合成与分泌来调节血浆HDL浓度。然而，关于GL对肝细胞（HEP）摄取和处理HDL的影响却知之甚少。为研究此问题，我们通过在大鼠HEP培养物中对碘标记的无载脂蛋白E（apo E）的HDL3进行特异性结合和内化，研究了地塞米松（DEX）对高亲和力HDL结合位点表达的影响。在无DEX培养48小时的细胞中，HDL3的特异性结合和内化减少了60%。在10^(-7)和10^(-5) mol/L浓度下，DEX可防止这种减少，使特异性结合和内化维持在与对照水平相当的程度（24小时时）。在培养的HEP表面发现了Kd为20微克/毫升的HDL结合位点。在10^(-7)和10^(-5) mol/L浓度的DEX存在下，HEP表现出更大的结合能力（125对45纳克/毫克细胞蛋白）。在10^(-9)至10^(-7) mol/L浓度之间，激素的作用呈剂量依赖性，在10^(-7)时趋于平稳。更高浓度不会导致特异性结合和内化进一步增加。从培养基中撤除激素后，在接下来的24小时内，配体的特异性结合减少了60%。为研究糖皮质激素缺乏对体内肝脏摄取HDL的影响，在接种后2小时，对从肾上腺切除大鼠（AER）分离的HEP培养物中的特异性结合和内化进行了研究。（摘要截短至250字）
