Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.34 (lipoprotein lipase)
7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A subnormal activity of postheparin plasma hepatic lipase was demonstrated in nine of 16 patients with familial type II hypercholesterolemia. On the other hand, in patients with combined hyperlipidemia (type II b) the hepatic lipase activity was mostly in upper normal range. The postheparin plasma lipoprotein lipase activity was normal in both patient groups. It is suggested that the low hepatic lipase activity may have a role in the patholgenesis of one form of familial hypercholesterolemia.
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PMID:Low postheparin plasma hepatic lipase activity in familial type IIa hyperlipoproteinemia. 18 Aug 67

We sought to investigate effects of lipoprotein lipase (LpL) on cellular catabolism of lipoproteins rich in apolipoprotein B-100. LpL increased cellular degradation of lipoprotein(a) (Lp(a)) and low density lipoprotein (LDL) by 277% +/- 3.8% and 32.5% +/- 4.1%, respectively, and cell association by 509% +/- 8.7% and 83.9% +/- 4.0%. The enhanced degradation was entirely lysosomal. Enhanced degradation of Lp(a) had at least two components, one LDL receptor-dependent and unaffected by heparitinase digestion of the cells, and the other LDL receptor-independent and heparitinase-sensitive. The effect of LpL on LDL degradation was entirely LDL receptor-independent, heparitinase-sensitive, and essentially absent from mutant Chinese hamster ovary cells that lack cell surface heparan sulfate proteoglycans. Enhanced cell association of Lp(a) and LDL was largely LDL receptor-independent and heparitinase-sensitive. The ability of LpL to reduce net secretion of apolipoprotein B-100 by HepG2 cells by enhancing cellular reuptake of nascent lipoproteins was also LDL receptor-independent and heparitinase-sensitive. None of these effects on Lp(a), LDL, or nascent lipoproteins required LpL enzymatic activity. We conclude that LpL promotes binding of apolipoprotein B-100-rich lipoproteins to cell surface heparan sulfate proteoglycans. LpL also enhanced the otherwise weak binding of Lp(a) to LDL receptors. The heparan sulfate proteoglycan pathway represents a novel catabolic mechanism that may allow substantial cellular and interstitial accumulation of cholesteryl ester-rich lipoproteins, independent of feedback inhibition by cellular sterol content.
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PMID:Mechanisms by which lipoprotein lipase alters cellular metabolism of lipoprotein(a), low density lipoprotein, and nascent lipoproteins. Roles for low density lipoprotein receptors and heparan sulfate proteoglycans. 132 15

A series of cyclic imides, which possess a bulkier N-ring structure than phthalimide and saccharin, were shown to suppress LDL receptor binding, internalization and degradation of isolated rat hepatocytes, foam cells, human fibroblasts and mouse macrophages. The HDL receptor binding and internalization was accelerated in hepatocytes but not in other tissue types. In general, the HDL receptor activity and degradation was reduced by the cyclic imides. The in vivo studies with selected cyclic imides supported this finding in that 125I-LDL was not cleared from serum as rapidly as the control after 14 days of treatment, whereas 125I-HDL was cleared more rapidly by treated rats. The tissue uptake of 125I-LDL amd 125I-HDL was generally reduced in the treated rat tissues after 14 days dosing. These agents did not suppress HMG-CoA reductase activity in any of the tissue cell lines. A correlation existed between lower LDL receptor activity and stimulated HMG-CoA reductase activity in cells. The cyclic imides suppressed the activities of acyl-CoA cholesterol-acyltransferase, sn-glycerol-3-phosphate acyl transferase, and heparin-induced tissue lipoprotein lipase. Neutral cholesterol ester hydrolase activity and protein synthesis were markedly stimulated by the cyclic imides in the aorta foam cells, but not the other cell types.
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PMID:The effects of cyclic imides on lipoprotein receptor binding and degradation of rat and human cells and effects on regulatory enzymes of lipid metabolism. 132 61

During lipolysis of chylomicron triacylglycerol by lipoprotein lipase, arachidonic acid (AA) esters are hydrolyzed at a slower rate than the predominant 16-18 carbon fatty acid esters. The further metabolism of the AA that is hereby enriched in the chylomicron remnant acylglycerols has not been investigated. In the present study, we examined the low density lipoprotein (LDL) dependent and independent metabolism of [14C]AA present in chylomicron remnants in the human hepatoma cell line Hep G2. Mesenteric duct cannulated rats were fed [14C]AA and [3H]cholesterol in corn oil, and the chyle obtained was injected intravenously into hepatectomized rats to form chylomicron remnants labeled with [14C]AA in the triacylglycerol (TG) and with 3H in the cholesteryl ester portion. The remnants were then incubated with Hep G2 cells. The uptake of [14C]AA within 2-4 h was similar to that of [3H]cholesteryl ester. After uptake into the cells, [14C]AA was preferentially incorporated into phospholipids, a high proportion being found in phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol. [14C]AA and [3H]cholesteryl ester uptake were influenced to similar extents by factors unknown to regulate the LDL receptor and by an anti-LDL receptor antibody. Addition of compactin thus increased the uptake of [14C]AA by 50% in 4 h and mevalonolactone decreased the uptake by 86%. Using an anti-LDL receptor antibody, 25.0% of [3H]cholesterol/cholesteryl ester and 37.7% of [14C]AA binding to the cells at 4 degrees C were blocked. There was no lipolysis of [14C]TG or [14C]diacylglycerol by lipase secreted into the medium during incubations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lipoprotein receptor mediated metabolism of [14C]arachidonic acid labeled chylomicron remnants by Hep G2 cells. 133 5

Lipoprotein lipase enhances binding at 4 degrees C of human plasma lipoproteins (chylomicrons, VLDL, intermediate density lipoprotein, LDL, and HDL3) to cultured fibroblasts and hepG-2 cells and to extracellular matrix. Heparinase treatment of cells and matrix reduces the lipoprotein lipase enhanced binding by 90-95%. Lipoprotein lipase causes only a minimal effect on the binding of lipoproteins to heparan sulfate deficient mutant Chinese hamster ovary cells while it promotes binding to wild type cells that is abolished after heparinase treatment. With 125I-LDL, lipoprotein lipase also enhances uptake and proteolytic degradation at 37 degrees C by normal human skin fibroblasts but has no effect in heparinase-treated normal cells or in LDL receptor-negative fibroblasts. These observations prove that lipoprotein lipase causes, predominantly, binding of lipoproteins to heparan sulfate at cell surfaces and in extracellular matrix rather than to receptors. This interaction brings the lipoproteins into close proximity with cell surfaces and may promote metabolic events that occur at the cell surface, including facilitated transfer to cellular receptors.
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PMID:Lipoprotein lipase enhances binding of lipoproteins to heparan sulfate on cell surfaces and extracellular matrix. 143 Feb 23

A simple, low-priced chromatographic system to generate plasma lipoprotein profiles from total human plasma was tested with plasma from normolipidemic subjects and patients with heterozygous familial hypercholesterolemia, hyper-alpha-lipoproteinemia, lipoprotein lipase deficiency, familial dysbetalipoproteinemia and familial lecithin-cholesterol-acyl-transferase deficiency. The system appears to be a good alternative to more expensive high-pressure liquid chromatography systems, notably in lipoprotein laboratories already provided with equipment for column chromatography. If a microplate photometer and a computer is available in the laboratory, the measurement of various lipids in 70-80 eluant fractions from the columns can be simplified.
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PMID:Generation of analytic plasma lipoprotein profiles using two prepacked superose 6B columns. 152 29

Lipoprotein kinetic studies have demonstrated that a large proportion of Sf 60-400 very low density lipoprotein (VLDL) is cleared directly from the circulation in Type IV hypertriglyceridemic subjects, at an unknown tissue site. The present studies were designed to investigate the role of hepatocytes in this process and to define the conditions, whereby Type IV Sf 60-400 VLDL would induce lipid accumulation in HepG2 cells. Type IV VLDL (Sf 60-400) failed to augment the total cholesterol, esterified cholesterol, or triglyceride content of HepG2 cells following 24-h incubations. Coincubation of bovine milk lipoprotein lipase (LPL) and Type IV VLDL with HepG2 cells induced a 3-fold increment in cellular esterified cholesterol mass (p less than 0.005) and a 7-fold increase in cellular triglyceride mass (p less than 0.005), compared to VLDL alone. The increased cellular lipid mass was associated with increased oleate incorporation into cellular cholesterol esters and triglycerides. Exogenous LPL hydrolyzed 76% of the VLDL triglyceride over 24 h. LPL action on Type IV VLDL was sufficient to promote cellular uptake of these lipoproteins, while elevated media-free fatty acid levels were not. Although HepG2 cells secrete apolipoprotein (apo) E, we assessed the role of VLDL-associated apoE in the lipid accumulation induced by VLDL plus LPL. ApoE-rich and apoE-poor Type IV VLDL subfractions induced similar increments in cellular esterified cholesterol in the presence of LPL, despite a 4-fold difference in apoE content. Sf 60-400 VLDL, from subjects homozygous for the defective apoE2, plus LPL, behaved identically to Type IV VLDL plus LPL. Type IV VLDL plus LPL, preincubated with anti-apoE (1D7) and apoB (5E11) monoclonal antibodies, known to block the binding of apoE and -B, respectively, to the LDL receptor failed to block lipid accumulation. In contrast, apoE-poor Type IV VLDL, apoE2 VLDL, and VLDL plus 1D7 were taken up poorly by J774 cells, cells that secrete LPL, but not apoE. These studies suggest that lipolytic remodeling of large Type IV VLDL by LPL is a prerequisite for their uptake by HepG2 cells and that HepG2 cell-secreted apoE rather than VLDL-associated apoE is the ligand involved in uptake.
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PMID:Lipolysis is a prerequisite for lipid accumulation in HepG2 cells induced by large hypertriglyceridemic very low density lipoproteins. 158 49

Chylomicron catabolism is known to be initiated by the enzyme lipoprotein lipase (triacylglycero-protein acylhydrolase, EC 3.1.1.34). Chylomicron remnants, produced by lipolysis, are rapidly taken up by the liver via an apolipoprotein E (apoE)-mediated, receptor-dependent process. The low density lipoprotein (LDL) receptor-related protein (LRP) has been suggested as the potential apoE receptor. We have analyzed the binding of human chylomicrons to HepG2 cells in the absence and presence of lipoprotein lipase. Bovine and human lipoprotein lipases were able to increase the specific binding of the chylomicrons by up to 30-fold. This effect was not dependent on lipolysis but appeared to be due to the lipase protein itself. It was not found when a structurally unrelated, bacterial lipase was used. Using beta-migrating very low density lipoproteins (beta-VLDLs), known as a good ligand for LRP, binding studies were performed on LDL receptor-negative human fibroblasts. The binding was increased 40-fold by addition of lipoprotein lipase. Crosslinking experiments on cells with 125I-labeled apoE liposomes or lipoprotein lipase showed that both proteins were able to bind to LRP on the cell surface. The binding of apoE to LRP was highly increased by the addition of lipase. We conclude that lipoprotein lipase strongly enhances the binding of apoE-containing lipoproteins to LRP and therefore might play an important role in chylomicron catabolism not only because of its lipolytic activity but also because of its structural properties.
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PMID:Lipoprotein lipase enhances the binding of chylomicrons to low density lipoprotein receptor-related protein. 165 40

The mechanism by which ethinyl estradiol (EE) decreases the concentration of lipids in the d less than 1.019 g/ml fraction (beta-very low density lipoprotein [beta-VLDL]) of homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits was studied. Treatment with EE increased the activity of hepatic lipase (HL) twofold to threefold in postheparin plasma and in liver biopsies. Postheparin plasma and adipose tissue lipoprotein lipase (LPL) activities were also increased twofold to fourfold after EE. The effects of EE on HL and LPL activities were associated with a threefold to sixfold elevation in liver HL mRNA and a fourfold elevation in adipose tissue LPL mRNA steady-state levels, pointing to an effect of EE on HL and LPL gene transcription. EE also increased liver low density lipoprotein (LDL) receptor mRNA levels threefold to fivefold. These results suggest a concerted action of LPL, HL, and the LDL receptor in the removal of beta-VLDL in homozygous WHHL rabbits with a defective LDL receptor. In addition, the content of apolipoprotein E in the d less than 1.019 g/ml fraction changed toward normal after EE. Because the remaining particles contained apolipoprotein B-100 almost exclusively, it is likely that apolipoprotein E-containing beta-VLDLs are preferentially removed. This may be the result of the increased activity of LPL and HL influencing the conformation of apolipoprotein E on the beta-VLDL particle in such a way that it is directly removed from the circulation, possibly by the induced LDL receptor.
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PMID:Increased removal of beta-very low density lipoproteins after ethinyl estradiol is associated with increased mRNA levels for hepatic lipase, lipoprotein lipase, and the low density lipoprotein receptor in Watanabe heritable hyperlipidemic rabbits. 165 30

Oral administration of cholestyramine to adult male hamsters not only induced a marked decrease in plasma concentrations of cholesterol and LDL but had a similar lowering effect on plasma triacyglycerol and VLDL concentrations. The hypotriglyceridaemic effects of resin administration were not due to an increase in lipoprotein lipase, as post-heparin plasma lipoprotein lipase activities were unchanged, but rather to a 35% decrease in VLDL synthesis. Measurement of the disappearance rate of apolipoprotein B from VLDL after i.v. injection of 125I-labelled hamster or human VLDL into control and cholestyramine-fed recipient animals showed a 2-times lower T1/2 in the drug-treated animals. The fraction of VLDL apolipoprotein B, recovered at any time after injection in the LDL, was equal or higher in cholestyramine-fed animals as compared to controls. These data indicate that the lowering in plasma LDL by cholestyramine in male hamsters is due not only to LDL receptor up-regulation but also to a lower rate of VLDL synthesis. No indications were found for a decreased efficiency of VLDL to LDL conversion in cholestyramine-fed animals.
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PMID:Effects of cholestyramine on lipoprotein levels and metabolism in Syrian hamsters. 173 48


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