Lipoprotein substrates of lipoprotein lipase and hepatic triacylglycerol lipase from human post-heparin plasma

Musliner, Thomas; Herbert, Peter N.; Kingston, Marguerite J.

doi:10.1016/0005-2760(79)90029-8

Cited by 102 publications

(26 citation statements)

References 31 publications

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“…1). While VLDL lipids are hydrolyzed more effectively by LpL than HL, IDL, and LDL lipids are significantly better substrates for HL than LpL (94). HL has a higher affinity for LDL than LpL and has the capability to act as a phospholipase as well, hence removing both core and surface components from the particle (90,95).…”

Section: Role Of Plasma Lipase Activities In Production Of Ldl From Tmentioning

confidence: 99%

Metabolic origins and clinical significance of LDL heterogeneity

Berneis

Krauss

2002

Journal of Lipid Research

779

633

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LDLs in humans comprise multiple distinct subspecies that differ in their metabolic behavior and pathologic roles. Metabolic turnover studies suggest that this heterogeneity results from multiple pathways, including catabolism of different VLDL and IDL precursors, metabolic remodeling, and direct production. A common lipoprotein profile designated atherogenic lipoprotein phenotype is characterized by a predominance of small dense LDL particles. Multiple features of this phenotype, including increased levels of triglyceride rich lipoprotein remnants and IDLs, reduced levels of HDL and an association with insulin resistance, contribute to increased risk for coronary heart disease compared with individuals with a predominance of larger LDL. Increased atherogenic potential of small dense LDL is suggested by greater propensity for transport into the subendothelial space, increased binding to arterial proteoglycans, and susceptibility to oxidative modification. Large LDL particles also can be associated with increased coronary disease risk, particularly in the setting of normal or low triglyceride levels. Like small LDL, large LDL exhibits reduced LDL receptor affinity compared with intermediate sized LDL. Future delineation of the determinants of heterogeneity of LDL and other apoB-containing lipoproteins may contribute to improved identification and management of patients at high risk for atherosclerotic disease. -Berneis, K. K., and R. M. Krauss. Metabolic origins and clinical significance of LDL heterogeneity.

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Section: Role Of Plasma Lipase Activities In Production Of Ldl From Tmentioning

confidence: 99%

Metabolic origins and clinical significance of LDL heterogeneity

Berneis

Krauss

2002

Journal of Lipid Research

779

633

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“…Aviram et al (19) concluded that LPL enhances LDL uptake and degradation in both fibro-blasts and human monocyte-derived macrophages via LDL receptors. They suggest that LPL's lipolytic activity is necessary for its ability to enhance LDL degradation, but they did not study the effect of LPL on the catabolism of VLDL, which is a better substrate for LPL than LDL (25). Several investigators determined that LPL-mediated LDL degradation is independent of the LDL receptor and is not regulated by factors affecting LDL receptor expression (20 -22).…”

Section: Lipoprotein Lipase (Lpl)mentioning

confidence: 99%

Lipoprotein Lipase Binds to Low Density Lipoprotein Receptors and Induces Receptor-mediated Catabolism of Very Low Density Lipoproteins

Medh

Bowen

Fry

et al. 1996

Journal of Biological Chemistry

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Lipoprotein lipase (LPL)1 catalyzes the hydrolysis of triglycerides in plasma chylomicrons and very low density lipoproteins (VLDL) (1-4). In humans, deficiency of either LPL or apolipoprotein (apo) CII, an essential cofactor for LPL's lipolytic activity, results in severe elevation in plasma chylomicrons and large VLDL (5). In addition to its lipolytic actions, LPL is also a ligand for receptors belonging to the family of low density lipoprotein (LDL) receptors, including LDL receptorrelated protein (LRP)/␣ 2 -macroglobulin (␣ 2 M) receptor, GP330/ LRP-2, and VLDL receptors (6 -13). LPL can influence lipoprotein catabolism by simultaneously binding to both lipoproteins and these cell surface receptors (6 -13). LPL promotes VLDL catabolism in LDL receptor-lacking mutant fibroblasts, and ligands specific for LRP inhibit LPL-stimulated VLDL degradation (9). LPL promotes lipoprotein binding to purified LRP (9) and GP330/LRP-2 (11) in solid-phase assays. Argraves et al. (12) demonstrated that transfection of PEA13 cells with VLDL receptors enhances their ability to internalize and degrade 125 I-LPL. Takahashi et al. (13) showed that in chinese hamster ovary cells co-transfected with the VLDL receptor and LPL, binding and degradation of 125 I-VLDL is much greater than in cells transfected with VLDL receptor alone. These studies demonstrate that LPL-dependent VLDL catabolism is mediated by LRP (6 -10), GP330/LRP-2 (10, 11), and VLDL receptors (12, 13). LPL also binds to cell surface heparan sulfate proteoglycans (3, 14 -16). LPL binding to either heparan sulfate proteoglycans or receptors can be separated from its lipolytic activity as indicated by studies with LPLC, the carboxyl-terminal, noncatalytic domain of LPL (8,17,18).

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“…HL functions both as a cell surface ligand for lipoprotein uptake and as a lipolytic enzyme that mediates the clearance of triacylglycerol from the blood stream and the conversion of VLDL to LDL (2)(3)(4)(5)(6)(7)(8)(9). It has been known for over five decades that displacement of lipolytic enzymes from cell surface binding sites with heparin results in rapid hydrolysis of triacylglycerol-rich lipoproteins in lipemic serum (10,11).…”

mentioning

confidence: 99%

HDL regulates the displacement of hepatic lipase from cell surface proteoglycans and the hydrolysis of VLDL triacylglycerol

Ramsamy

Boucher

Brown

et al. 2003

Journal of Lipid Research

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We have previously shown that hepatic lipase (HL) is inactive when bound to purified heparan sulfate proteoglycans and can be liberated by HDL and apolipoprotein A-I (apoA-I), but not by LDL or VLDL. In this study, we show that HDL is also able to displace HL directly from the surface of the hepatoma cell line, HepG2, and Chinese hamster ovary cells stably overexpressing human HL. ApoA-I is more efficient at displacing cell surface HL than is HDL, and different HDL classes vary in their ability to displace HL from the cell surface. Human hepatic lipase (HL) is a 64 kDa glycoprotein anchored by heparan sulfate proteoglycans (HSPGs) to the surface of endothelial cells and hepatocytes (1). HL functions both as a cell surface ligand for lipoprotein uptake and as a lipolytic enzyme that mediates the clearance of triacylglycerol from the blood stream and the conversion of VLDL to LDL (2-9). It has been known for over five decades that displacement of lipolytic enzymes from cell surface binding sites with heparin results in rapid hydrolysis of triacylglycerol-rich lipoproteins in lipemic serum (10, 11). However, it is still commonly believed that both HL and lipoprotein lipase (LPL) are catalytically active when bound to cell surface proteoglycans and that this association may indeed enhance the lipolysis of triacylglycerol [as reviewed in ref. (12)].This common view is in fact counterintuitive to the interfacial catalytic models proposed for lipases, which have shown a clear requirement for enzyme hopping or shuttling between substrates for optimal hydrolysis (13,14). In agreement with this view, we showed that HL is active only when it is free in solution, and indeed is completely inactive when bound to pure HSPG (15). In addition, we showed that HL could be displaced from a pure HSPG matrix by HDL, and specifically by apolipoprotein A-I (apoA-I), but not by LDL or VLDL. In the present study, we have reevaluated this displacement phenomenon in HepG2 cells and in a Chinese hamster ovary cell line stably overexpressing human HL (CHO-hHL). As with our pure HSPG studies, we show that only apoA-I and HDL are able to displace cell surface HL. We further show that different HDL classes vary in their ability to displace HL, and demonstrate that the lowest density fractions (HDL 2 ) have the greatest capacity to remove HL from the cell surface and intracellular compartments.In addition to their ability to displace cell surface HL, we have previously reported that apoA-I and HDL directly affect HL-mediated triacylglycerol hydrolysis, and showed that the rate of triacylglycerol hydrolysis is regulated by the amount of HDL in plasma (15). This observation sugAbbreviations: CHO-hHL, Chinese hamster ovary cell line stably overexpressing human hepatic lipase; ECM, extracellular matrix; EMEM, Eagle's minimal essential medium; FAF-BSA, essentially fatty acid-free BSA; HL, hepatic lipase; HRP, horseradish peroxidase; HSPG, heparan sulfate proteoglycan; [ 3 H]TG, [ 3 H]triolein; MAb, monoclonal antibody; pen/strep, penicillin/...

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Lipoprotein substrates of lipoprotein lipase and hepatic triacylglycerol lipase from human post-heparin plasma

Cited by 102 publications

References 31 publications

Metabolic origins and clinical significance of LDL heterogeneity

Metabolic origins and clinical significance of LDL heterogeneity

Lipoprotein Lipase Binds to Low Density Lipoprotein Receptors and Induces Receptor-mediated Catabolism of Very Low Density Lipoproteins

HDL regulates the displacement of hepatic lipase from cell surface proteoglycans and the hydrolysis of VLDL triacylglycerol

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