Reagan J W, Miller L R, St Clair R W
Department of Pathology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27103.
J Biol Chem. 1990 Jun 5;265(16):9381-91.
The contribution of receptor-dependent and receptor-independent mechanisms for low density lipoprotein (LDL) clearance in vivo was determined in White Carneau and Show Racer pigeons fed either cholesterol free or cholesterol containing diets. The methylation of pigeon LDL resulted in the inhibition of recognition by the LDL receptor which allowed its use as a tracer of receptor-independent clearance. The fractional catabolic rate (FCR) of radiolabeled LDL in 20 control pigeons (means +/- S.E., 0.277 +/- 0.013 pools/h) was approximately seven times faster than for methylated LDL indicating that 86% of the total LDL clearance occurred by a receptor-mediated process. Total LDL clearance was reduced by 27% (FCR = 0.202 +/- 0.012 pools/h) in 14 cholesterol-fed pigeons, but receptor-mediated mechanisms were still responsible for 80% of the total LDL clearance. LDL uptake by individual tissues was measured using the residualizing label 125I-tyramine cellobiose. The liver was the primary site of LDL clearance in both control and cholesterol-fed birds. LDL receptors were active in every tissue examined and accounted for over 85% of the LDL clearance in the liver and over 90% in the adrenal gland. Consistent with the whole body LDL clearance findings, cholesterol-feeding did not significantly reduce receptor-mediated clearance of 125I-tyramine cellobiose-LDL by the liver or any of the other tissues. Hepatic sterol synthesis, however, was reduced by greater than 90% in cholesterol-fed animals. These data are consistent with the conclusion that LDL clearance in vivo in pigeons is mediated primarily by an LDL receptor-like mechanism that shows little down-regulation with hypercholesterolemia even though cholesterol synthesis is efficiently down-regulated.
在以无胆固醇或含胆固醇饲料喂养的白卡诺鸽和赛鸽中，确定了体内低密度脂蛋白（LDL）清除的受体依赖性和非受体依赖性机制的作用。鸽LDL的甲基化导致其被LDL受体识别的能力受到抑制，这使其能够用作非受体依赖性清除的示踪剂。20只对照鸽中放射性标记LDL的分解代谢率（FCR）（均值±标准误，0.277±0.013池/小时）比甲基化LDL快约7倍，这表明86%的总LDL清除是通过受体介导的过程发生的。14只喂食胆固醇的鸽子的总LDL清除率降低了27%（FCR = 0.202±0.012池/小时），但受体介导的机制仍占总LDL清除的80%。使用残留标记物125I - 酪胺纤维二糖测量各个组织对LDL的摄取。肝脏是对照鸽和喂食胆固醇鸽中LDL清除的主要部位。LDL受体在每个检查的组织中均有活性，在肝脏中占LDL清除的85%以上，在肾上腺中占90%以上。与全身LDL清除结果一致，喂食胆固醇并未显著降低肝脏或任何其他组织对125I - 酪胺纤维二糖 - LDL的受体介导清除。然而，喂食胆固醇的动物肝脏中甾醇合成减少了90%以上。这些数据与以下结论一致：鸽体内LDL清除主要由一种类似LDL受体的机制介导，即使胆固醇合成被有效下调，该机制在高胆固醇血症时也几乎没有下调。
