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)

Apolipoprotein E (ApoE; "arginine-rich" polypeptide) strongly inhibited both C-I and C-II activated lipoprotein lipases but not the protamine insensitive triglyceride lipase. Inhibition of lipoprotein lipases by ApoE in contrast to inhibition by C-III was not reversed to any significant extent by either increased concentration of activator or triglyceride in the substrate. Our previous studies have shown that in a type III hyperlipoproteinemia (broad-beta-disease) a post-heparin plasma lipoprotein lipase activated by C-II polypeptide of lipoprotein C is decreased in enzyme activity and exhibits an impaired ability to hydrolyze triglycerides in very low density lipoproteins. Type III patients are characterized by elevated concentrations of ApoE in the serum. The data presented in this report suggest that the decreased C-II activated lipoprotein lipase may be further aggravated by increased ApoE levels. Since this enzyme is involved in the catabolism and removal of lipoproteins, decreased activity of C-II activativated lipoprotein lipase may presumably be responsible for increased ApoE.
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PMID:Is decreased activity of C-II activated lipoprotein lipase in type III hyperlipoproteinemia (broad-beta-disease) a cause or an effect of increased apolipoprotein E levels? 18 83

The application of isoelectric focussing on a gel-stabilized layer for the separation of the Tris-urea-soluble apolipoproteins of very low density lipoproteins has been described. This method in one step, allows the separation of most apolipoproteins, which were then analyzed and characterized. Apolipoproteins CII and CI were isolated as single protein bands with apparent pI of 5.0 and 6.5, respectively. Apolipoprotein CII was biologically active and could activate lipoprotein lipase. Apolipoprotein CIII was separated into several protein bands with pI ranging from 4.7 to 5.1 as a function of their number of sialic acid residues. Apolipoprotein E was isolated and characterized into five polymorphic bands with pI of 5.7, 5.8, 5.9, 6.0, and 6.2, respectively.
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PMID:Preparative isoelectric focussing of apolipoproteins C and E from human very low density lipoproteins. 22 32

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

Human patients with familial hypercholesterolemia (FH) and Watanabe heritable hyperlipidemic rabbits (WHHL), while lacking normal receptors recognizing low-density lipoproteins (LDL), are said to have normal clearance of chylomicrons. In the present study, emulsions with a similar lipid composition to chylomicrons were injected intravenously in homozygous WHHL rabbits and normal control rabbits fed diet with low or high cholesterol. Radioactive labels tracing emulsion triolein and cholesteryl oleate were both removed rapidly from the bloodstream, with the removal rate of triolein always faster than that of cholesteryl oleate. This pattern was similar to the clearance of normal chylomicrons in rabbits or rats, and was consistent with the formation of remnant lipoproteins after hydrolysis of emulsion triolein by lipoprotein lipase, followed by hepatic uptake of the remnants. The removal of cholesteryl oleate was significantly slower in WHHL rabbits than in normal controls, suggesting that the absence of LDL receptor function led to impaired remnant clearance. Measured in post-heparin plasma, the activity of lipoprotein lipase was decreased in WHHL rabbits, but this was not associated with clear evidence of defective lipolysis of emulsion triolein. Apolipoprotein E did not appear to be deficient in WHHL rabbits. Plasma devoid of lipoproteins less than 1.006 g/ml from WHHL and normal control rabbits transferred similar amounts of apolipoprotein E to chylomicron-like emulsions after incubation. Impaired clearance of chylomicron remnants possibly contributes to the hypertriglyceridemia of WHHL rabbits and to accelerated atherogenesis when the function of LDL receptors is defective.
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PMID:Defective plasma clearance of chylomicron-like lipid emulsions in Watanabe heritable hyperlipidemic rabbits. 199 43

The human monocyte-like cell line, THP-1, differentiated into macrophage-like cells on the addition of a phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate. During the course of differentiation of THP-1 cells, the level of transcripts of the apolipoprotein E gene increased. Apolipoprotein E mRNA increased by more than a hundred times compared to the level prior to differentiation. The apolipoprotein E mRNA reached the maximal level on day 2 after the addition of the phorbol ester and then gradually decreased. After the level had decreased to half the maximal value on day 4 it remained constant. The time course of apolipoprotein E secretion, which showed a peak on day 2, was parallel to that of apolipoprotein E protein synthesis. Furthermore, the time course of apolipoprotein E protein synthesis showed a similar profile to that of the apolipoprotein E transcript level. This indicates that the induction of apolipoprotein E expression by the phorbol ester is due mainly to the increase in the number of transcripts. The synthesis of apolipoprotein E protein was reduced by about 60% on treatment of the differentiated THP-1 cells with 5 micrograms/ml of lipopolysaccharide. The presence of 5 micrograms/ml of lipopolysaccharide in the medium reduced the level of apolipoprotein E mRNA by about 50%. Thus the reduction in protein synthesis was mainly explained by the decrease in the level of apolipoprotein E transcripts. This reduction in the mRNA level caused by lipopolysaccharide was not mediated by the tumor necrosis factor or interleukin 1, which are known to reduce the transcriptional and post-transcriptional activity of lipoprotein lipase in adipocytes, respectively.
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PMID:Expression of the apolipoprotein E gene in a human macrophage-like cell line, THP-1. 260 2

Apolipoprotein E plays a major role in the uptake of chylomicrons and of very-low-density lipoprotein (VLDL) remnants by the liver. It has also been clearly demonstrated that apolipoprotein E rapidly and spontaneously exchanges between lipoproteins. To assess whether all lipoprotein-bound apolipoprotein E is available to participate in spontaneous transfer and/or exchange, the present study followed the fate of radiolabeled apolipoprotein E in an in vitro system. The results show that in vitro, apolipoprotein E can be considered as having both a spontaneously exchangeable pool and a nonexchangeable pool. Based upon specific radioactivity data, only a limited amount of apolipoprotein E originating in VLDL or in high-density lipoproteins (HDL) was capable of in vitro exchange with that in other lipoprotein fractions. Lipolysis of VLDL triacylglycerol by milk lipoprotein lipase, however, resulted in complete transfer of VLDL apolipoprotein E mass and radioactivity to HDL, supporting the potential for transformation of exchangeable apolipoprotein to a transferable pool in vivo. The results of these studies indicate that during the course of lipoprotein metabolism, conformational changes occur which alter the accessibility of apolipoprotein E. Such dynamic heterogeneity may have implications for the regulation of lipoprotein metabolism.
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PMID:In vitro metabolism of apolipoprotein E. 377 25

We have analysed by northern blotting and by in situ hybridization the expression patterns of eight different genes during the second half of mouse embryonic development and in adult mouse brain: we compared the messenger RNA levels of amyloid precursor protein and of the two amyloid precursor protein-like proteins 1 and 2 and we have analysed expression of apolipoprotein E and of its main receptor in brain, the alpha-2-macroglobulin/low density lipoprotein receptor-related protein and three other ligands: the proteinase inhibitor alpha-2-macroglobulin, the modifying enzyme lipoprotein lipase and the 44,000 molecular weight heparin binding protein, a ligand of unknown function. During embryogenesis the temporal expression pattern differs considerably for the three members of the amyloid precursor proteins. Total embryo messenger RNA levels of amyloid precursor protein and amyloid precursor protein-like protein 2 increased progressively, while amyloid precursor protein-like protein 1 messenger RNA showed a burst of synthesis between days 10 and 13 post-coitum. Significantly, expression of the alpha-2-macroglobulin/low density lipoprotein receptor-related protein and of its associated protein, the 44,000 molecular weight heparin binding protein, exhibited their most important increase very similar to that of amyloid precursor protein-like protein 1, between days 10 and 13 post-coitum. Apolipoprotein E, lipoprotein lipase and alpha-2-macroglobulin messenger RNA levels in total embryos increased progressively, beginning most pronounced at days 13, 15 and 17, respectively. In mouse embryos, in situ hybridization established amyloid precursor protein, amyloid precursor protein-like protein 2 and alpha-2-macroglobulin/low density lipoprotein receptor-related protein messenger RNA to be expressed in most organs, with the notable exception of the liver, while expression of the other studied proteins was much more restricted. Among adult mouse tissues, the genes investigated were expressed very prominently in brain, except for lipoprotein lipase and for the complete absence of alpha-2-macroglobulin messenger RNA. In adult mouse brain, the cortex and hippocampus exhibited strong signals for most genes analysed. Exceptions are lipoprotein lipase and apolipoprotein E messenger RNAs, and the absent alpha-2-macroglobulin messenger RNA. Several interesting features, similarities as well as differences, between brain tissue sections hybridized with probes for amyloid precursor protein, amyloid precursor protein-like proteins 1 and 2 and between alpha-2-macroglobulin/low density lipoprotein receptor-related protein and heparin binding protein-44 were observed and are described. The results are further discussed in view of the known or anticipated physiological functions of the proteins examined and of their possible role in the etiology of Alzheimer's disease.
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PMID:Expression in mouse embryos and in adult mouse brain of three members of the amyloid precursor protein family, of the alpha-2-macroglobulin receptor/low density lipoprotein receptor-related protein and of its ligands apolipoprotein E, lipoprotein lipase, alpha-2-macroglobulin and the 40,000 molecular weight receptor-associated protein. 754 71

Apolipoprotein E (apoE) is an important determinant for the liver uptake of triglyceride-rich lipoproteins and emulsions by the remnant receptor. In the current study, we assessed an additional role of apoE as modulator of the metabolism of triglyceride-rich lipoproteins in vitro and in vivo. Glycerol tri[3H]oleate [14C]cholesteryl oleate double-labeled triglyceride-rich emulsions were injected into fasted rats. The serum half-life of glycerol tri[3H]oleate was 3-fold faster (5.4 min) than that of [14C]cholesteryl oleate (16.7 min), confirming lipoprotein lipase (LPL)-mediated processing. To establish a specific effect of apoE on emulsion lipolysis rather than liver uptake, rats were functionally hepatectomized, and hypo(apo)lipoproteinemia was induced by 17alpha-ethinyl estradiol treatment. An apoE concentration-dependent inhibition of emulsion-triglyceride hydrolysis was observed, reaching a 14.8-fold increased half-life of glycerol tri[3H]oleate as compared with that in the absence of exogenous apoE. The mechanism and specificity of the effect of apoE on emulsion lipolysis by purified LPL was assessed in vitro. Addition of apoE to glycerol tri[3H]oleate-labeled emulsions led to a concentration-dependent inhibition of [3H]oleate release (9.5% residual LPL activity at 60 microg/ml apoE), while apoA-I was ineffective. The inhibitory effect of apoE was not abolished by reductive methylation of lysine residues, whereas selective modification of arginine residues by 1,2-cyclohexadione completely cancelled the inhibitory effect of apoE. It is concluded that apoE can specifically inhibit the LPL-mediated hydrolysis of emulsion triglycerides both in vitro and in vivo, and that arginine residues in apoE are essential for this effect. We suggest that in addition to its role in receptor recognition, apoE also modulates the LPL-mediated processing of triglyceride-rich lipoproteins.
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PMID:Apolipoprotein E effectively inhibits lipoprotein lipase-mediated lipolysis of chylomicron-like triglyceride-rich lipid emulsions in vitro and in vivo. 866 66

Tamoxifen, a nonsteroidal estrogen antagonist, has been widely used in a hormonal treatment for breast cancer. The side effects of tamoxifen are generally recognized to be mild. However, we experienced three cases of severe hypertriglyceridemia and/or hyperglycemia induced by tamoxifen. For normalization of their hypertriglyceridemia we need to stop giving tamoxifen. In one of three cases we analyzed her lipoprotein profile in detail with lipoprotein lipase activities and apolipoprotein E phenotype. The case was a 49 year-old woman. After 15 months of tamoxifen administration, she was diagnosed as severe hypertriglyceridemia. Consecutively, severe hyperglycemia was occurred to need insulin therapy. After tamoxifen withdrawal, her triglyceride and glucose levels improved. Her lipolytic enzyme was reduced during tamoxifen treatment. Apolipoprotein E phenotype was uncommon E4/2. Although hypertriglyceridemia was not considered to be a risk factor for coronary heart disease, a marked hypertriglyceridemia might occasionally produce severe lethal pancreatitis. We recommend that a periodic plasma lipid analysis is needed for patients treated with tamoxifen, especially for diabetic and hypertriglyceridemic patients, to avoid such complications.
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PMID:Severe hypertriglyceridemia caused by tamoxifen-treatment after breast cancer surgery. 946 33

Hyperlipidaemias are important risk factors for coronary heart disease. To prevent and treat the different forms of hyperlipidaemias it is important to understand lipoprotein metabolism. The current knowledge on lipoprotein metabolism is based on many different biochemical and metabolic studies which are summarized here for a clinically orientated overview. Exogenous fat is transported in chylomicrons from the intestine to the liver. After entry in the blood stream the chylomicrons are hydrolyzed by the endothelial-bound lipoprotein lipase. The chylomicron remnants are rapidly taken up into the liver via the LDL receptor and the LDL receptor-related protein. Apolipoprotein E and lipoprotein lipase are the recognition signals for these receptors. The liver utilizes the exogenous fat and can release surplus lipids via VLDL into the blood. The VLDL are another substrate for lipoprotein lipase. The remaining VLDL remnants can either be taken up into the liver or are hydrolyzed to LDL. LDL delivers cholesterol to all body cells via the LDL receptor. The level of LDL cholesterol is regulated by the amount of LDL receptor, and defects in the LDL receptor molecule lead to hypercholesterolaemia. The level of triglyceride-rich remnants is regulated by the amount and activity of lipoprotein lipase and defects in this enzyme cause mixed hyperlipidaemias. Both these forms of hyperlipoproteinaemias are the most frequent and represent major risk factors for arteriosclerosis.
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PMID:Lipoprotein metabolism. 951 38


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