Tissue sites of degradation of native and reductively methylated [14C]sucrose-labeled low density lipoprotein in rats. Contribution of receptor-dependent and receptor-independent pathways.
Low density lipoprotein (LDL) is catabolized by both receptor-dependent and receptor-independent pathways; methylated LDL (MeLDL) is catabolized only by receptor-independent mechanisms. Rats were injected with either LDL or MeLDL labeled with [14C]sucrose and the tissue sites of degradation were determined 24 h later. On degradation, the 14C-labeled ligand remains trapped intracellularly as a cumulative measure of degradation. The fractional catabolic rate (FCR) of [14C]sucrose-MeLDL was lower than that of [14C]sucrose-LDL (0.056 +/- 0.015 versus 0.118 +/- 0.025 h-1, p less than 0.01). Liver was the predominant site of catabolism of both LDL and MeLDL; more than 85% of catabolism was attributable to parenchymal cells in both cases. The fraction of the plasma LDL pool "cleared" per tissue weight per unit of time was determined for individual tissues. The differences in these rates for LDL and MeLDL are an approximation of receptor-mediated uptake of LDL. According to this method, 67.4% of hepatic uptake was attributable to receptors, as was 69.5% of adrenal, 65.4% of ovarian, 52.4% of intestinal, and 44.2% of renal uptake. In other studies, rats were continuously infused with LDL to down-regulate and saturate receptor prior to injection of labeled LDL or MeLDL. Rats infused with LDL exhibited a lower FCR for [14C]sucrose-LDL compared to controls (0.077 versus 0.120 h-1); the FCR for sucrose-MeLDL was unchanged by LDL infusion. The fractional degradation rate of [14C]sucrose-LDL by individual tissues was lowered by LDL infusion in liver, adrenal, ovary, and intestine (41.4, 57.3, 23.1, and 32.4% lower than controls, respectively). The determination of receptor dependency by this independent approach supports the conclusions reached using [14C]sucrose-LDL and [14C]sucrose-MeLDL in normolipemic animals.
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D005260:Female; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008433:Mathematics; D008954:Models, Biological; D010053:Ovary / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011973:Receptors, LDL; D012867:Skin / Q000378:metabolism; D013395:Sucrose / Q000378:metabolism*; D014018:Tissue Distribution
C035247:LDL-sucrose; D008077:Lipoproteins, LDL; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; D013395:Sucrose; D002784:Cholesterol