Cellular differences in lipoprotein lipase-mediated uptake of low density lipoproteins

• Published in: The Journal of biological chemistry Vol. 269; no. 18; pp. 13129 - 13135
• Main Authors: Obunike, J.C, Edwards, I.J, Rumsey, S.C, Curtiss, L.K, Wagner, W.D, Deckelbaum, R.J, Goldberg, I.J
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 06-05-1994
• Subjects: ABSORCION; ABSORPTION; Acetylation; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Cell Line; CHIMIORECEPTEUR; DEGRADACION; DEGRADATION; FIBROBLASTE; FIBROBLASTOS; Fibroblasts - metabolism; Fundamental and applied biological sciences. Psychology; GENERO HUMANO; GENRE HUMAIN; Heparan Sulfate Proteoglycans; HEPARINA; HEPARINE; Heparitin Sulfate - metabolism; Humans; Kinetics; Lipoprotein Lipase - metabolism; LIPOPROTEINA LIPASA; LIPOPROTEINAS; LIPOPROTEINE; LIPOPROTEINE LIPASE; Lipoproteins, LDL - metabolism; Lipoproteins, myelin; MACROFAGOS; MACROPHAGE; Macrophages - metabolism; PROTEINAS; PROTEINE; Proteins; PROTEOGLICANOS; PROTEOGLYCANE; Proteoglycans - metabolism; QUIMIORECEPTORS; Receptors, LDL - physiology; Up-Regulation; Human; Enzyme; Esterases; Lipoprotein lipase; Lipoprotein; Metabolism; Uptake; Carboxylic ester hydrolases; Lipoprotein LDL; Membrane receptor; Hydrolases; Fibroblast; Macrophage
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(17)36808-4

Lipoprotein lipase (LPL) increases the cellular uptake and degradation of LDL by fibroblasts and macrophages via a heparin-sensitive process. The roles of the LDL receptor, LDL receptor-related protein (LRP), and proteoglycans in this process were studied. In up-regulated human fibroblasts, LPL increased degradation of 125I-density lipoprotein LDL) (5 microgram/ml) only 30% during a 6-h incubation at 37 degrees C. Monoclonal antibody 47 (which interacts with the receptor binding region of apoB) decreased LDL degradation 93% in the absence of LPL, but did not reduce the LPL-mediated increase in degradation. In contrast, addition of the 39-kDa receptor-associated protein (RAP) caused a 43% decrease in the LPL-dependent LDL degradation in non-up-regulated fibroblasts. Monoclonal antibody 47 did not decrease LDL degradation by THP-1 macrophages and RAP caused a 13% decrease in LPL-mediated LDL degradation. LPL also increased the association of acetyl LDL with the surface of the macrophages but did not increase acetyl LDL degradation. The kinetics of LPL-mediated LDL metabolism in macrophages was then compared with that in fibroblasts. The half-lives of cell surface LDL and LPL during a subsequent 37 degrees C incubation were approximately 1 h in THP-1 cells versus 6 h in fibroblasts. In addition, 50% of the 125I-LDL and 30% of the 125I-LPL were degraded within 3 h. After metabolic labeling of THP-1 proteoglycans with SO41 30% of peri-cellular heparan sulfate was lost between 2-4 h of the chase period. Therefore, some of the LPL-mediated LDL degradation in the THP-1 cells could be accounted for by internalization of cell surface proteoglycans. We conclude that LRP, but not the LDL receptor, is involved in LPL-mediated degradation of LPL in fibroblasts. This process is much more rapid in THP-1 cells and in addition to LRP may involve other receptors and internalization of proteoglycans