Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.34 (lipoprotein lipase)
 7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Complex phenotypes such as serum lipid concentrations involve numerous genes and require the analysis of the combined effects of these gene products. We modeled the interactions of six key lipid metabolism genes by means of differential equations. We tested the model by inserting the effects of known mutations in the low-density lipoprotein receptor gene and the lipoprotein lipase gene, as well as the effects of a high-fat diet, and observed that the predictions corresponded very well to published measurements. Models such as the one that we present here will become indispensable for analyzing and understanding the effects of variation in multiple genes.
J Mol Med (Berl) 2000
PMID:A pathway model of lipid metabolism to predict the effect of genetic variability on lipid levels. 1114 Mar 72

Hypertriglyceridemia is a frequent complication accompanying the treatment of patients with either retinoids or rexinoids, [retinoid X receptor (RXR)-selective retinoids]. To investigate the cellular and molecular basis for this observation, we have studied the effects of rexinoids on triglyceride metabolism in both normal and diabetic rodents. Administration of a rexinoid such as LG100268 (LG268) to normal or diabetic rats results in a rapid increase in serum triglyceride levels. LG268 has no effect on hepatic triglyceride production but suppresses post-heparin plasma lipoprotein lipase (LPL) activity suggesting that the hypertriglyceridemia results from diminished peripheral processing of plasma very low density lipoproteins particles. Treatment of diabetic rats with rexinoids suppresses skeletal and cardiac muscle but not adipose tissue LPL activity. This effect is independent of changes in LPL mRNA. In C2C12 myocytes, LG268 suppresses the level of cell surface (i.e., heparin-releasable) LPL activity without altering LPL mRNA. This effect is very rapid (t(1/2) = 2 h) and is blocked by the transcriptional inhibitor actinomycin D. These studies demonstrate that RXR ligands can have dramatic effects on the post-translational processing of LPL and suggest that skeletal muscle may be an important target of rexinoid action. In addition, these data underscore that the metabolic consequences of RXR activation are distinct from either retinoic acid receptor or peroxisome proliferator-activated receptor activation.
Mol Pharmacol 2001 Feb
PMID:Metabolic effects of rexinoids: tissue-specific regulation of lipoprotein lipase activity. 1116 Aug 50

Cell surface heparan sulfate proteoglycans are involved in several aspects of the lipoprotein metabolism. Most of the biological activities of these proteoglycans are mediated via interactions of their heparan sulfate moieties with various protein ligands, including lipoproteins and lipases. The binding of lipoproteins to heparan sulfate is largely determined by their apoprotein composition, and apoproteins B and E display the highest affinity for heparan sulfate. Interactions of lipoproteins with heparan sulfate are important for the cellular uptake and turnover of lipoproteins, in part by enhancing the accessibility of lipoproteins to lipoprotein receptors and lipases. Apoprotein B may interact with receptors without involving heparan sulfate. Heparan sulfate has been further implicated in presentation and stabilization of lipoprotein lipase and hepatic lipase on cell surfaces and in the transport of lipoprotein lipase from extravascular cells to the luminal surface of the endothelia. In atherosclerosis, heparan sulfate is intimately involved in several events important to the pathophysiology of the disease. Heparan sulfate thus binds and regulates the activity of growth factors, cytokines, superoxide dismutase and antithrombin, which contribute to aberrant cell proliferation, migration and matrix production, scavenging of reactive oxygen radicals and thrombosis. In this review we discuss the various roles of heparan sulfate proteoglycans in vascular biology, with emphasis on interactions of heparan sulfate with lipoproteins and lipases and the molecular basis of such interactions.
Cell Mol Life Sci 1999 Nov 30
PMID:Cell surface heparan sulfate proteoglycans and lipoprotein metabolism. 1121 44

Kinetic parameters of chicken and rat lipoprotein lipase (LPL) were determined in the incubation in vitro with various monoacid triacylglycerol emulsion and plasma lipoproteins. In rat- and chicken-LPL there is an inverse relationship between the hydrolytic rate by both LPL and the increased acyl-chain unsaturation of monoacid triacylglycerol; C18:1>C18:2>C18:3. The rat LPL catalyzed hydrolysis of saturated monoacid triaclyglycerol increased with an increase of chain length as C16>C14>C12, whereas in chicken LPL hydrolytic rate of C12 was higher than C14 and C16 triaclyglycerol. Vmax of rat- and chicken-LPL for chylomicron and VLDL were higher but apparent Km for those were lower than other lipoproteins. In chicken, Vmax and apparent Km of LPL for VLDL were almost the same as those for chylomicron, whereas in rat, Vmax of LPL for VLDL was twice that of chylomicron with the same apparent Km. The chicken and rat VLDL with different particle size prepared by Bio-Gel A50 gel chromatography were similarly hydrolyzed by LPL, while the hydrolysis of small chicken-chylomicron particles was inclined to be higher than that of the large particles. These results show species differences between chickens and rats in the substrate specificity of LPL.
Comp Biochem Physiol A Mol Integr Physiol 1998 Feb
PMID:Species differences in substrate specificity of lipoprotein lipase purified from chickens and rats. 1124 4

To investigate the role of insulin receptor substrate 1 (IRS-1) and IRS-2, the two ubiquitously expressed IRS proteins, in adipocyte differentiation, we established embryonic fibroblast cells with four different genotypes, i.e., wild-type, IRS-1 deficient (IRS-1(-/-)), IRS-2 deficient (IRS-2(-/-)), and IRS-1 IRS-2 double deficient (IRS-1(-/-) IRS-2(-/-)), from mouse embryos of the corresponding genotypes. The abilities of IRS-1(-/-) cells and IRS-2(-/-) cells to differentiate into adipocytes are approximately 60 and 15%, respectively, lower than that of wild-type cells, at day 8 after induction and, surprisingly, IRS-1(-/-) IRS-2(-/-) cells have no ability to differentiate into adipocytes. The expression of CCAAT/enhancer binding protein alpha (C/EBPalpha) and peroxisome proliferator-activated receptor gamma (PPARgamma) is severely decreased in IRS-1(-/-) IRS-2(-/-) cells at both the mRNA and the protein level, and the mRNAs of lipoprotein lipase and adipocyte fatty acid binding protein are severely decreased in IRS-1(-/-) IRS-2(-/-) cells. Phosphatidylinositol 3-kinase (PI 3-kinase) activity that increases during adipocyte differentiation is almost completely abolished in IRS-1(-/-) IRS-2(-/-) cells. Treatment of wild-type cells with a PI 3-kinase inhibitor, LY294002, markedly decreases the expression of C/EBPalpha and PPARgamma, a result which is associated with a complete block of adipocyte differentiation. Moreover, histologic analysis of IRS-1(-/-) IRS-2(-/-) double-knockout mice 8 h after birth reveals severe reduction in white adipose tissue mass. Our results suggest that IRS-1 and IRS-2 play a crucial role in the upregulation of the C/EBPalpha and PPARgamma expression and adipocyte differentiation.
Mol Cell Biol 2001 Apr
PMID:Essential role of insulin receptor substrate 1 (IRS-1) and IRS-2 in adipocyte differentiation. 1125

The filamentous fungus Nectria haematococca (anamorph Fusarium solani f. sp. pisi) resides in soil, and attacks pea seedlings in the area of the underground epicotyl and upper tap root, causing foot rot disease. We detected lipase activity during in vitro growth of N. haematococca. Subsequently, a lipase gene was cloned and functionally characterised by heterologous expression in Saccharomyces cerevisiae. The full-length cDNA of 1152 bp was cloned using a 3' RACE-PCR approach coupled with cDNA library screening. The genomic clone, comprising an ORF of 999 bp interrupted by two introns of 56 and 64 bp, was isolated from a newly constructed lambda phage library. Analysis of the deduced protein sequence revealed the presence of a typical signal peptide at the N-terminus, and of the three conserved amino acids forming the active site of lipases. The lipase of N. haematococca has a low degree of similarity to the lipases from Humicola lanuginosa (37.2%), Rhizomucor miehei (21.6%), Rhizopus delemar (23.1%), Rhizopus niveus (25.9%), and to mono- and diacylglycerol lipase from Penicillium camembertii (30.8%), and very high similarity (94.6%) to a lipase from Fusarium heterosporum. The lipase from N. haematococca shows maximal activity at 37 degrees C and pH 8.0. Based on Southern analysis, the lipase clone represents a single-copy gene in N. haematococca. Expression analysis was performed by RT-PCR. In vitro, the lipase gene shows a low basal expression, but is highly inducible by lipase substrates, and repressed by glucose. During plant infection, transcripts of this fungal lipase gene were detected 4, 8, and 10 days after infection.
Mol Genet Genomics 2001 Apr
PMID:Cloning and expression analysis of NhL1, a gene encoding an extracellular lipase from the fungal pea pathogen Nectria haematococca MP VI (Fusarium solani f. sp. pisi) that is expressed in planta. 1136 31

Relative quantitative reverse transcription-polymerase chain reaction (rqRT-PCR), which allows an accurate quantification of the amount of mRNA in samples potentially differing in the quality of their RNA preparation, was used to quantify lipoprotein lipase (LPL) mRNA in ovine adipose tissue. A comparative evaluation of four rqRT-PCR procedures was carried out. The amount of LPL mRNA was assayed relative to either that of gamma-actin (ACT) or cyclophilin (CYC) mRNA, used as endogenous standard. Independent (INACT and INCYC procedures) or simultaneous (COACT and COCYC procedures) amplifications have been compared. Fluorescently labelled primers yielded PCR products which were quantitatively analysed using an automated DNA sequencer. After optimizing the PCR cycle number and verifying that the amounts of ACT and CYC mRNA varied only weakly according to the nutritional conditions studied, we have tested the ability of the four procedures to quantify specific variations in LPL mRNA. The repeatability of each step and the overall assay reproducibility were also examined. The COACT and INCYC procedures were finally retained to accurately quantify LPL mRNA in AT from nine underfed or refed ewes, and gave highly correlated results (r=0.98, p<0.01). In addition, significant correlations (r=0.83, p<0.01 and r=0.92, p<0.01 for COACT and INCYC, respectively) were observed with the LPL activity in AT.
Mol Cell Probes 2001 Aug
PMID:A fluorescent reverse transcription-polymerase chain reaction assay to quantify the lipoprotein lipase messenger RNA. 1151 52

The purpose of this study was to determine whether HindIII restriction polymorphism found in intron 8 of lipoprotein lipase gene is associated with the onset of myocardial infarction (MI) in Russians and Tartars living in Bashkortostan. HindIII polymorphism was investigated by the polymerase chain reaction in myocardial infarction survivors (males aged under 55 years (98 Russians and 68 Tartars) and in controls (53 Russians and 80 Tartars). The distribution of genotypes and allele frequencies in the controls were as follows: the frequencies of genotypes HindIII(-/-), HindIII(+/-), and HindIII(+/+) in Russians (3.77, 49.06, and 47.17%, respectively) did not differ from those in Tartars (7.50, 51.24, and 41.25%, respectively), while the frequency of HindIII(-) allele was 28.30% in Russians and 33.13% in Tartars. Among Tartars, the HindIII(+/+) genotype was more common in myocardial infarction survivors than in controls (OR 2.03). In the Russians this genotype was not associated with the risk of MI. The frequencies of HindIII(+/+) genotype and allele HindIII(+) were significantly higher (OR 8.96 and 6.71, respectively) and frequencies of HindIII(+/-) genotype and allele HindIII(-) were lower (OR 0.13 and 0.15) in Russian patients with repeated MI. These findings indicate that HindIII polymorphism may be a genetic risk factor for MI before 55 years of age in the Tartars and for repeated MI in Russians. This association prompts genotyping of HindIII polymorphism for predicting MI recurrence in Russian survivors after MI.
Mol Gen Mikrobiol Virusol 2001
PMID:[HindIII polymorphism of lipoprotein lipase gene and risk of myocardial infarction]. 1153 94

The metabolism of high density lipoprotein cholesteryl esters (HDL CE) was studied in the pony, an animal species without plasma cholesteryl ester transfer protein (CETP) activity. Studies were done in ponies fed a low- (1.5% fat, w/w) and a high-fat diet (11.5%, w/w fat). The ponies fed the high-fat diet had higher plasma HDL CE concentrations (1.08+/-0.15 vs. 0.84+/-0.11 mmol/l, mean+/-S.D., n=6, P<0.01) and plasma lipoprotein lipase (LPL) activities (14.3+/-4.0 vs. 5.7+/-3.4 micromol free fatty acids (FFA)/ml per h, P<0.05) than those on the low-fat diet. Plasma triacylglycerol (TAG) concentrations were lower on the high-fat diets (0.129+/-0.043 vs. 0.180+/-0.050 mmol/l), but these differences were not statistically significant. There was a negative correlation between the levels of plasma TAG (r=0.598, P<0.05) and VLDL CE (r=0.658, P<0.05) on the one hand and the HDL CE concentrations on the other hand. The transport rates of HDL CE were not significantly different between ponies fed high-fat (0.029+/-0.008 mmol HDL CE/h per l plasma) and those fed low-fat diets (0.024+/-0.004). HDL CE were transferred to low density lipoproteins (LDL) and we calculated that the percentage of LDL CE derived from HDL was 0.69+/-0.13 in the ponies fed the low-fat diet and 0.53+/-0.05 in the ponies fed the high-fat diet (P<0.05). The results of these in vivo studies suggest that in ponies, similarly as reported in rats and pigs, HDL CE can be transferred to LDL despite the absence of plasma CETP activity, and that the magnitude of this transfer is related to the levels of HDL CE as induced by the amount of fat in the diet.
Comp Biochem Physiol B Biochem Mol Biol 2001 Sep
PMID:High density lipoprotein cholesteryl ester metabolism in the pony, an animal species without plasma cholesteryl ester transfer protein activity: transfer of high density lipoprotein cholesteryl esters to lower density lipoproteins and the effect of the amount of fat in the diet. 1154 85

The 39-44 kDa protein known as the receptor-associated protein binds to members of the low density lipoprotein receptor family and is found within cells that express these receptors. The receptor-associated protein has been shown to prevent premature binding of ligands to the receptors in the endoplasmic reticulum and to promote proper folding and transport of the receptors in the secretory pathway. In the thyroid, megalin (a low-density lipoprotein receptor family member) serves as an endocytic receptor for thyroglobulin. Here we present evidence that the receptor-associated protein can bind to thyroglobulin, which suggests a novel function of the receptor-associated protein, namely binding of certain megalin ligands possibly during the biosynthetic pathway. In solid-phase assays thyroglobulin was shown to bind to the receptor-associated protein with moderately high affinity (mean between K(d) and K(i) = 39.8 nM), in a calcium-dependent and saturable manner. The receptor-associated protein also bound to a native carboxyl-terminal 230-kDa thyroglobulin polypeptide, which markedly reduced binding of intact thyroglobulin to the receptor associated protein, indicating that the receptor-associated protein binding sites of thyroglobulin are located in the carboxyl-terminal portion of the molecule. In addition to thyroglobulin, the receptor-associated protein specifically bound to another megalin ligand, namely lipoprotein lipase. Because lipoprotein lipase markedly reduced receptor-associated protein binding to thyroglobulin, we concluded that the receptor-associated protein uses the same binding site/s to bind to thyroglobulin and lipoprotein lipase. Evidence of thyroglobulin binding to the receptor-associated protein was also obtained in vivo and in cultured thyroid cells. Thus, anti-receptor-associated protein antibodies precipitated intact thyroglobulin from extracts prepared from rat thyroids and cultured thyroid cells (FRTL-5 cells). Chase experiments after inhibition of protein synthesis in FRTL-5 cells showed that thyroglobulin interacts with the receptor-associated protein shortly after the beginning of thyroglobulin biosynthesis.
Mol Endocrinol 2001 Oct
PMID:Binding of the low density lipoprotein receptor-associated protein (RAP) to thyroglobulin (Tg): putative role of RAP in the Tg secretory pathway. 1157 14


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