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)

1. Lipoprotein lipase was purified from pig myocardium by a two-step purification procedure involving (a) the formation of an enzyme-substrate complex and (b) affinity chromatography on Sepharose which contained covalently linked heparin. The purified enzyme gave in sodium dodecyl sulphate-polyacrylamide-gel electrophoresis one main band with an apparent molecular weight of 73 000. The enzyme, which was purified 70 000-fold, had a specific activity of 860 mumol of unesterified fatty acid liberated/h per mg of protein. 2. The purified enzyme hydrolysed [14C]triolein emulsions in the absence of added cofactors but its activity was increased fivefold by adding normal human serum. Of the low-density lipoprotein apoproteins only apolipoprotein CII could be substituted for serum in activating the enzyme. This lipase had maximum activity at 0.05-0.15 M-NaCl. Heparin increased the activity of the purified enzyme twofold at low concentrations, but high concentrations inhibited. The triglyceride lipase of pig myocardium thus resembles lipoprotein lipase purified from adipose tissue and from plasma, but is clearly different from pig hepatic triglyceride lipase.
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PMID:Purification and characterization of lipoprotein lipase from pig myocardium. 123 78

Heparin and heparin partially depolymerized by enzymic digestion were separated into six size fractions. Hep 1 (tetrasaccharides), with a mean M(r) of 1200, did not release significant amounts of either lipoprotein lipase (LPL) or hepatic lipase (HL) on intravenous injection into rats. Hep 2 (mainly octa- and deca-saccharides), with a mean M(r) of 2400-3000, released both lipases. To evoke the same plasma activity of LPL and HL required about 10 times more by weight, or about 40 times more molecules, of this heparin than of hep 5 (mean M(r) 12,000, similar to conventional heparin). Hep 5 impeded binding and degradation of 125I-labelled bovine LPL by perfused rat livers. In contrast, hep 2 had no detectable effect on these processes. This demonstrates a difference between the sites in the liver that mediate binding, uptake and degradation of LPL, and the extrahepatic sites that bind functional LPL, and the hepatic sites that bind functional HL. After injection of 3.25 mg of hep 5/kg body weight, plasma LPL activity rapidly rose and then remained high for at least 1 h. With hep 2, plasma LPL also rose rapidly, but then decreased to almost basal by 1 h. When a labelled triacylglycerol emulsion was injected 1 h after the heparins, the fractional catabolic rate was enhanced in the rats that had received conventional heparin, as expected from the high plasma LPL activity, but decreased compared with controls in rats that had received hep 2, indicating that available LPL had been depleted through enhanced transport to and uptake in the liver.
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PMID:Interaction of size-fractionated heparins with lipoprotein lipase and hepatic lipase in the rat. 149 11

The influence of heparin administration on the protein binding of lidocaine was investigated in this study. Epidural anesthesia was conducted in 20 patients undergoing vasoconstructive surgery, and the changes of lidocaine concentration and its protein binding ratio after heparin administration were estimated. Protein binding ratio of lidocaine decreased rapidly after the commencement of heparin injection until attaining the minimal rate of 50.3 +/- 8.8%, and it then recovered gradually. There was a distinct negative correlation between the reduction in protein binding ratio of lidocaine and the increase of non-esterified fatty acid (NEFA) based on the activated lipoprotein lipase after heparin administration. This reduction of protein binding ratio after heparin was in safety range so that practically no dangerous adverse reaction was seen in these patients. The detailed mechanism was elucidated in an in vitro study. Normal concentration of NEFA (300 microEq.l-1) increased the protein binding ratio of lidocaine, and high concentration of NEFA (1800 microEq.l-1) decreased the ratio on human serum albumin (HSA). Heparin (1.0 unit.ml-1) itself, however, showed no influence for protein binding ratio onto HSA. Concerning alpha 1-acid glycoprotein (AAG), NEFA did not show any influence on the binding ratio, and heparin decreased it little. Consequently, it can be said that the protein binding ratio of lidocaine was mainly affected by NEFA concentration.
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PMID:[The influence of heparin administration on the plasma protein binding of lidocaine during epidural anesthesia]. 156 May 80

Streptozotocin-induced diabetes reduced cellular lipoprotein lipase (LPL) activity in cardiac myocytes from rat hearts and decreased the heparin-induced release of LPL into the medium. This effect of diabetes was rapidly reversed by in vivo treatment with insulin (5 U iv for 1 h); administration of insulin in vivo to control rats also increased heparin-releasable LPL activity. In contrast, in vitro addition of insulin to control and diabetic myocytes did not alter either cellular or heparin-releasable LPL activities. Insulin stimulated glucose oxidation and protein synthesis in control and diabetic myocytes. Decavanadate (0.05-1 mM) or vanadyl ion (0.5 mM) enhanced the release of LPL into the medium. Heparin- and decavanadate-induced release of LPL was not additive, and heparin pretreatment reduced the subsequent release of LPL by decavanadate. Decavanadate displaced LPL bound to heparin-Sepharose and increased LPL release into the perfusate of hearts. Therefore, decavanadate can mimic heparin in its effect on LPL. The absence of a direct in vitro effect of insulin on LPL in cardiac myocytes suggests that insulin may require some other in vivo factor or that diabetes-induced changes in LPL activity are secondary to some other metabolic factor.
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PMID:Lipoprotein lipase release from cardiac myocytes is increased by decavanadate but not insulin. 159 Mar 76

The hydrolysis of triglycerides in plasma lipoproteins is mediated by lipoprotein lipase (LPL) that is bound to vascular endothelial cells. The specific endothelial cell surface protein(s) with which LPL associates has not been characterized. To identify this LPL binding protein(s), radioiodinated cell surface proteins from cultured bovine aortic endothelial cells were chromatographed using bovine LPL-Sepharose. A single radioiodinated protein of apparent molecular mass 220 kDa was specifically retained by the gel and eluted with 0.4 M NaCl. A LPL-binding protein of similar size was obtained after metabolic labeling of the cellular proteoglycans with 35SO4, indicating that the 220-kDa protein is a proteoglycan. After heparitinase or nitrous acid treatments the molecular mass of the LPL-binding protein decreased to approximately 50 kDa, suggesting that it contains heparin sulfate chains. A 220-kDa protein from the basal cell surface was also identified using LPL-Sepharose chromatography. 125I-LPL was cross-linked to the endothelial cell surface using ethylene glycobis (succinimidylsuccinate). A single ligand-receptor complex, approximately 350 kDa, was obtained. Heparin and unlabeled LPL decreased the cross-linking of radioiodinated LPL to the cell surface receptor. To examine whether the receptor mediates the internalization of cross-linked 125I-LPL, cells containing 125I-LPL complexed to the surface were incubated at either 37 or at 4 degrees C. The amount of 125I-LPL internalized by the cells was 74% greater at 37 degrees C than at 4 degrees C. This suggested that LPL cross-linked to the receptor was internalized in a temperature-dependent manner. Thus, a 220-kDa heparan sulfate proteoglycan functions as an endothelial cell surface receptor for LPL.
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PMID:Identification and characterization of the endothelial cell surface lipoprotein lipase receptor. 165 30

Heparin is used as standard anticoagulant in the extracorporeal circuit of hemodialysis. Widespread use of this drug revealed several potentially adverse effects, such as release of lipoprotein lipase and hepatic lipase from the endothelial surface. Recently it was found that anticoagulatory potency and provocation of adverse effects are linked to different subfractions of heparin. A heparin subfraction of 4000 to 6000 Daltons rather specifically inhibits factor Xa and therefore has a very high antithrombotic potency. Its effects on release of lipases are minor. During a four year period five patients on maintenance hemodialysis were treated with this low molecular weight heparin (LMWH) subfraction. Additionally, another five patients successively received standard heparin, LMWH and again standard heparin. At all circumstances during treatment with LMWH there was a significant (0.001 less than P less than 0.05) reduction both of cholesterol and triglyceride blood concentrations. LMWH is efficient in avoiding clotting in extracorporeal circuit during hemodialysis in doses of 17 to 95 U/kg (initial dose) and 7 to 20 U/kg/hr (continuous dose).
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PMID:Reduced lipid concentrations during four years of dialysis with low molecular weight heparin. 166 3

Apolipoprotein E (apoE) is an important constituent of plasma lipoproteins and a ligand for several lipoprotein receptors. It is produced mainly in the liver but also in several peripheral tissues like brain, adrenal glands, kidney, and macrophages. Some of these tissues also coexpress lipoprotein lipase (LPL), an important enzyme in the metabolism of lipids and lipoproteins. This suggested a possible coordinate expression of these genes and led us to analyze whether adipocytes, a major source of LPL, could also synthesize apoE. Northern blotting experiments showed that apoE mRNA is found in differentiated mouse 3T3-L1 adipocytes as well as biopsies of human adipose tissue maintained in organ culture but not in undifferentiated 3T3-L1 preadipocytes. [35S]Methionine pulse-labeling experiments revealed that apoE protein is produced in human adipose tissue and differentiated mouse 3T3-L1 adipocytes but not in preadipocytes. In biosynthetic labeling experiments, most apoE was found to be cell associated even after prolonged chase periods. Heparin treatment of the cultured cells did not enhance apoE secretion. During differentiation of 3T3-L1 cells, the onset of apoE gene expression was later than that of LPL. The apoE mRNA and intracellular apoE protein concentrations increased linearly with time of differentiation, at least through day 11, whereas LPL showed highest expression at day 7 and then declined. The increase in apoE mRNA correlated with the cellular lipid content. Inhibition of lipid accumulation in differentiated cells by biotin deprivation decreased apoE expression. Cholesterol-loading experiments suggested that apoE mRNA expression is regulated by the intracellular free cholesterol content of 3T3-L1 adipocytes. In contrast, the LPL mRNA level was not influenced by biotin deprivation or cholesterol loading. Human recombinant tumor necrosis factor, a potent inhibitor of LPL gene transcription, had no effect on adipocyte apoE mRNA levels. Therefore, although apoE and LPL are both expressed in adipocytes in a differentiation-dependent manner, the time course of their expression differs as do their responses to cellular lipid content and tumor necrosis factor. We conclude that these genes are not coordinately regulated in adipocytes.
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PMID:Apolipoprotein E gene expression in mouse 3T3-L1 adipocytes and human adipose tissue and its regulation by differentiation and lipid content. 170 37

This study was designed to understand the reasons for the increase in serum pseudocholinesterase activity in diabetes mellitus. Streptozotocin-induced diabetic rats were used for the study. Serum pseudocholinesterase activity increased with the induction of diabetes (381.5 units/l +/- 11.8) compared to the non-diabetic rats (243.1 units/l +/- 7.2). Serum triglycerides, total low density lipoprotein and glycerol also increased concurrently with the development of diabetes. Insulin treatment of the diabetic rats normalized serum glucose concomitant with the reduction of pseudocholinesterase activity, triglycerides, total low density lipoprotein and glycerol. Heparin injection appeared to activate lipoprotein lipase in the diabetic rats by showing a marked fall in serum triglyceride and total low density lipoprotein levels but not in pseudocholinesterase activity. Administration of tetraisopropylpyrophosphoramide a specific pseudocholinesterase inhibitor, inhibited serum and adipose tissue pseudocholinesterase activity by greater than 80% and liver greater than 50%. Concurrent with the inhibition of pseudocholinesterase activity serum triglyceride, low density lipoprotein and glycerol decreased significantly. In normal rats treatment with tetraisopropylpyrophosphoramide also reduced serum lipoproteins markedly, while glycerol only showed a marginal decrease. Glycerol was used as a marker of adipose tissue lipolysis and total low density lipoprotein which is defined as lipoproteins of density less than 1.063 (LDL + VLDL).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship between serum pseudocholinesterase and triglycerides in experimentally induced diabetes mellitus in rats. 186 86

We showed previously that net secretory output of apolipoprotein B (apo B) from cultured human hepatoma cells (HepG2) is regulated by rapid reuptake of nascent lipoproteins before they have diffused away from the vicinity of the cells. We now sought to determine if the nascent lipoproteins could be remodeled to enhance or impede reuptake. We found that lipoprotein lipase (LpL), an enzyme that hydrolyzes lipoprotein triglyceride, reduced HepG2 output of apo B to one-quarter to one-half of control. The reduction was apparent during co-incubations as short as 2 h and as long as 24 h. Heparin, which blocks receptor-mediated binding of lipoproteins, abolished the effect of LpL on apo B output, without causing enzyme inhibition. To assess uptake directly, we prepared labeled nascent lipoproteins. LpL tripled the cellular uptake of labeled nascent lipoproteins, from 15.2% +/- 0.7% to 48.7% +/- 0.3% of the total applied to the cells. Cellular uptake of 125I-labeled anti-LDL receptor IgG was unaffected by LpL; thus, LpL enhanced reuptake by altering lipoproteins, not receptors. Because LpL is present in the space of Disse in the liver, we conclude that LpL may act on newly secreted lipoproteins to enhance reuptake in vivo. LpL deficiency would reduce local reuptake of apo B, which would appear as overproduction, thereby providing a mechanistic link between partial LpL deficiency and familial combined hyperlipidemia.
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PMID:Lipoprotein lipase modulates net secretory output of apolipoprotein B in vitro. A possible pathophysiologic explanation for familial combined hyperlipidemia. 191 80

We have analyzed the binding of lipoprotein lipase (LPL) to the subendothelial extracellular matrix produced by cultured endothelial cells. Binding was linear up to a concentration of 0.5 microgram/ml (10 nM) enzyme used in this study, and equilibrium was achieved after 2 h of incubation with bovine 125I-LPL at 4 degrees C. Heparin and heparan sulfate effectively inhibited the binding of LPL to extracellular-matrix-coated plates; chondroitin sulfate had no effect, while high concentrations of dermatan sulfate or keratan sulfate inhibited binding of LPL to extracellular matrix by only 40%. Basic fibroblast growth factor (bFGF) did not affect LPL binding, while antithrombin-III (AT-III) caused up to a 50% inhibition of enzyme binding to extracellular matrix. alpha-Thrombin. 5.10(-6) M, and its esterolytically inactive derivative, DIP-alpha-thrombin, effectively inhibited binding of LPL to extracellular-matrix-coated plates. alpha-Thrombin was also able to release the extracellular-matrix-bound LPL in an active form. Extracellular-matrix-bound LPL detached into medium containing triolein emulsion and/or serum, and was catalytically active after being released. Extracellular-matrix-bound LPL lost 30% of its activity following incubation at 37 degrees C for 4 h. in contrast to soluble LPL which lost 75% of its activity. It is plausible to conclude from these data that in vivo the subendothelial basement membrane, similarly to extracellular matrix, sequesters and stabilizers LPL secreted into the subendothelial space by non-endothelial cells, and thus may play an important role in determining the route of LPL from its site of synthesis to its site of action.
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PMID:Interaction of lipoprotein lipase with subendothelial extracellular matrix. 230 16


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