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)

The possibility that diabetes reduces functional, heparin-releasable lipoprotein lipase (HR-LPL) activity on the coronary vasculature of perfused hearts by altering endothelial binding sites for the enzyme was examined by measuring the binding and subsequent heparin-induced release of exogenous lipoprotein lipase purified from bovine milk (mLPL). Rat hearts were first perfused with heparin (5 U/mL) for 5 min to displace endogenous HR-LPL into the perfusate. The subsequent perfusion of control hearts with 0.05-2 micrograms/mL mLPL resulted in a progressive increase in bound exogenous enzyme that could be released by a second heparin perfusion. Induction of an acute, insulin-deficient model of diabetes (100 mg/kg streptozotocin 4-5 days prior to heart perfusions) reduced endogenous HR-LPL activity, but the binding and heparin-induced release of mLPL (0.5 microgram/mL) were the same as measured in control hearts. Therefore, diabetes does not alter low-affinity, high-capacity proteoglycan binding sites for mLPL on the endothelium of perfused hearts.
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PMID:Endothelial binding sites for lipoprotein lipase are not diminished in perfused hearts from diabetic rats. 902 78

Cyclophosphamide administration into fasted rabbits induces a hypertriglyceridaemia and a defect in vascular lipoprotein lipase. Heart LPL activity was more than 50% decreased after antimitotic treatment in fasted animals. The tissue distribution of lipoprotein lipase activity was followed in heart using recycling perfusion. Cyclophosphamide administration resulted in a profound decline in the heparin-releasable lipoprotein lipase activity, concordant with a higher recovery in the residual heart tissue. The effects were more pronounced in fasted than in fed animals. In agreement, the proportion of neosynthesized [35S]methionine-labelled lipoprotein lipase released by heparin was decreased by 50% following antimitotic treatment. The lipolysis of very low density lipoprotein-labelled triacylglycerols was found 2.5-fold reduced in hearts from cyclophosphamide-treated rabbits as compared to controls. These results suggest that a defective secretion of lipoprotein lipase may contribute to the poor expression of lipolytic activity in the vascular bed and to the occurrence of hypertriglyceridaemia during cyclophosphamide treatment.
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PMID:Impaired secretion of heart lipoprotein lipase in cyclophosphamide-treated rabbit. 908 4

The effect of the apolipoprotein C-II/C-III1 ratio on the capacity of purified bovine milk lipoprotein lipase to hydrolyse triglycerides was measured in a controlled model of pyrene-labeled nonanoyltriglycerides (1-2 ditetradecyl 3-pyrene nonanoyl glyceride) monolayer vesicles. Monolayer was composed of triglycerides, a non-hydrolysable phospholipid ether and cholesterol, a model system where the quality of the interface can be controlled. LPL released fatty acids from pyrene-triglycerides which were transferred from the lipoprotein structure to albumin. This transfer induces a decrease in the excimer production and in the excimer fluorescence intensity. Apolipoprotein C-II and C-III0 and C-III1 were purified from apolipoprotein VLDL. The 2 fragments, C-III1 A (peptide 1-40) and C-III1 B (peptide 41-79), were obtained after thrombin cleavage. Apolipoproteins C-III0 and C-III1 had a similar inhibitory effect on LPL. Inhibition with apo C-III0 or apo C-III1 was 85% of full LPL activity without inhibitor: Apo C-III1 B inhibited 62% of basal activity. It was 27% less effective than apo C-III1. Fragment C-III1 A did not inhibit LPL. The effect of change in both apo C-II (0-0.6 microM) and apo C-III1 (0-1.0 microM) on triglyceride hydrolysis shows the importance of the apo C-II/C-III1 ratio for the release of free fatty acids from triglycerides by LPL. The activating effect of apo C-II in the absence of the apo C-III inhibitor was maximal at 0.06 microM. No further activation was obtained between 0.06 and 0.30 microM. Higher concentrations decreased LPL activity. Apo C-III1 (0.1 microM) decreased the maximum activation by apo C-II from 0.0196 to 0.063 nmol/min/nmol LPL. Higher concentrations of apo C-III1 (0.1-0.5 microM) required higher apo C-II concentrations (0.30 microM instead of 0.06 microM) for maximal activation than when apo C-III1 was absent. The activity of the enzyme without apo C-II was decreased by 65% by 0.12 microM apo C-III1. Increasing the apo C-II/apo C-III1 ratio from 0.1 to 1, increased the activation of the enzyme by a given apo C-II concentration. Moreover, for a given apo C-II/C-III1 ratio, the LPL activation increased with the apo C-II concentration (between 0 and 0.010 microM), until a plateau was reached. This is important, as the change in the C-II/C-III1 ratio is not the only factor affecting LPL activity, and inhibition by apo C-III1 also depends on the overall quantity of apolipoproteins. Extrapolation of these results suggests that hyperlipoproteinemia seems to be more likely due to overproduction of VLDL, than to a decrease in lipoprotein lipase activity.
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PMID:Effect of the apolipoprotein C-II/C-III1 ratio on the capacity of purified milk lipoprotein lipase to hydrolyse triglycerides in monolayer vesicles. 912 10

The relationship between insulin-mediated glucose disposal and fasting insulin and triglyceride (TG) concentrations, plasma post-heparin lipoprotein lipase (PH-LPL) activity and mass, and adipose tissue LPL activity, mass, and mRNA content was defined in 19 non-diabetic men. Insulin-mediated glucose uptake [as assessed by determining the steady-state plasma glucose (SSPG) concentration during a continuous infusion of somatostatin, insulin, and glucose] was significantly correlated with fasting TG concentration (r = 0.54, p < 0.02), plasma PH-LPL activity (r = -0.52, p < 0.03) and mass (r = -0.49, p < 0.03), and adipose tissue LPL mRNA content (r = -0.68, p < 0.001). Comparable relationships were also seen when fasting insulin concentration was substituted for SSPG. Although adipose tissue LPL and mass correlated with each other (r = 0.76, p < 0.001) in a fasting state, they were not related to any other variable measured. Using in vivo and molecular biology techniques, these data demonstrate that the more insulin resistant an individual, the lower the level of plasma PH-LPL activity and mass, and the higher the plasma TG concentration. Since lower concentrations of adipose tissue mRNA were also directly correlated with plasma PH-LPL mass (r = 0.57, p < 0.01), and inversely with plasma TG concentration (r = -0.68, p < 0.001) as well as SSPG (r = -0.68, p < 0.001), it can be postulated that the relationship between insulin resistance and LPL activity and plasma TG concentration is associated with the inability of insulin to stimulate the transcription or to increase the intracellular mRNA stability of adipose tissue LPL in insulin resistant individuals.
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PMID:Relationship between insulin-mediated glucose disposal and regulation of plasma and adipose tissue lipoprotein lipase. 924 8

An increased adherence of leukocytes to the vascular endothelium appears to be a crucial event in the development of atherosclerosis. The role of endothelial cell adhesion molecules is gaining increasingly interest in this context. Several studies show an influence of lipoproteins, especially low-density-lipoproteins on adhesion molecule stimulation. The aim of our study was to analyze the atherogenic potential of postprandially elevated serum triglyceride levels by investigating the impact of postprandial lipoproteins (chylomicrons (CH, isolated 4 h after a standard oral lipid load)) on the expression of E-selectin (endothelial leukocyte adhesion molecule-1, ELAM-1) and VCAM-1 (vascular cell adhesion molecule-1). In addition we used chylomicrons that had been incubated with lipoprotein lipase (50 U/ml) for 3 h (CH-LPL). The endotoxin lipopolysaccharide (LPS) served as positive control for adhesion molecule stimulation. Human umbilical vein endothelial cells (HUVEC) were incubated with the samples for 4 h and expression of E-Selectin and VCAM-1 was determined by ELISA. The expression of E-selectin was induced by LPS (530 +/- 64% compared to the basal activity (= 100%)) and by CH (342 +/- 94%); CH-LPL had no effect on E-Selectin expression. VCAM-1 expression was stimulated by LPS (395 +/- 221%) and similarly by CH-LPL (322 +/- 136%) but considerably stronger by CH (1245 +/- 324). In summary, chylomicrons induced an enhancement of the expression of both adhesion molecules, which closely resembled or even exceeded the endotoxin-induced stimulation. Interestingly, this effect was diminished or even reversed after incubation with LPL.
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PMID:Chylomicrons induce E-selectin and VCAM-1 expression in endothelial cells. 928 41

This study evaluates the effects of insulin versus glibenclamide on lipoprotein metabolism at comparable levels of blood glucose control, in particular on the concentration and distribution of VLDL subfractions and lipolytic enzyme activities in nine NIDDM men (aged 56 +/- 3 years, BMI 26.5 +/- 0.9 kg/m2) (means +/- SE) participating in a crossover study. After a 3-week washout period, patients were randomly assigned to 2-month treatment periods (insulin or glibenclamide); thereafter, each patient crossed to the other treatment. At the end of each period, mean daily blood glucose (MDBG), HbA1e, plasma lipids, lipoproteins (VLDL, LDL, HDL), lipoprotein subfractions (VLDL1, 2, 3; HDL2, HDL3), and post-heparin lipase activities (lipoprotein lipase [LPL], hepatic lipase [HL]) were evaluated. Although glucose control was similar at the end of both periods (MDBG 8.3 +/- 0.3 vs. 7.9 +/- 0.3 mmol/l; HbA1c 7.4 +/- 0.3 vs. 7.0 +/- 0.2%, insulin versus glibenclamide), insulin compared with glibenclamide induced a significant reduction in plasma triglycerides (0.9 +/- 0.1 vs. 1.1 +/- 0.1 mmol/l, P < 0.05), VLDL triglycerides (50.1 +/- 12.2 vs. 63.6 +/- 12.3 mg/dl, P < 0.02), VLDL1 lipid concentration (24.9 +/- 7.5 vs. 39.9 +/- 9.5 mg/dl, P < 0.006), and increased HDL2 cholesterol (25.2 +/- 1.6 vs. 20.3 +/- 1.3 mg/dl, P < 0.03). In terms of VLDL percentage subfraction distribution, with insulin, there was a decrease in the larger subfractions (VLDL1 26.5 +/- 3.0 vs. 37.8 +/- 3.4%, P < 0.02) and an increase in the smallest (VLDL3 47.3 +/- 3.8 vs. 37.3 +/- 3.3%, P < 0.05). Moreover, HL activity was significantly lower after insulin than after glibenclamide (HL 247.2 +/- 22.3 vs. 263.5 +/- 22.6 mU/ml, P < 0.05). In conclusion, compared with glibenclamide, insulin treatment (independent of variations in glucose control) is able to decrease significantly plasma triglycerides, to increase HDL2 cholesterol, and to reduce only the concentration of the larger VLDL subfractions, with a consequent redistribution of their profile.
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PMID:Insulin and sulfonylurea therapy in NIDDM patients. Are the effects on lipoprotein metabolism different even with similar blood glucose control? 931 56

We studied 100 healthy monozygotic and 72 dizygotic twin pairs (mean age, 34 +/- 14 years) to test for genetic influences on blood lipids and to examine relevant gene loci. Total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triglyceride (TG) levels were determined after a 12-hour fast. Zygosity was determined with the use of microsatellite markers. Heritability estimates were conducted by using the lisrel 8 program; a sib-pair analysis was conducted by using the sibpal program. Linear regression analyses were carried out between identical-by-descent status and squared within-pair differences of TC, LDL-C, HDL-C, and TG values. Heritability estimates of the lipid serum concentrations ranged from .58 to .66. A significant linkage relationship was found for HDL-C (P = .008) and TGs (P = .05) with D8S261 on chromosome 8p. However, no linkage was found between any of the lipid variables and the lipoprotein lipase gene locus (LPL GZ14/15 and D8S282). Because D8S261 is located approximately halfway between the LPL and macrophage scavenger receptor genes, we examined the nearby markers D8S549 and D8S1731. Linkage was found for HDL-C and D8S549 (P = .001) and for HDL-C and D8S1731 (P = .04). On the other hand, we found no linkage between the LDL receptor gene locus and LDL-C serum concentrations nor between the LPL gene locus and the various other lipid fractions. Our data suggest a significant influence of the macrophage scavenger receptor gene locus on HDL-C and weak influence on TG levels. We suggest that inherited variability in the macrophage scavenger receptor gene has an influence on serum lipid concentrations.
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PMID:Heritability analysis of lipids and three gene loci in twins link the macrophage scavenger receptor to HDL cholesterol concentrations. 935 71

Loss of heterozygosity at chromosome 8p21-22 is common in human prostate cancer, suggesting the presence of one or more tumor suppressor genes at this locus. A homeobox gene that is expressed specifically in adult human prostate, NKX3.1, the expression of which is regulated by androgen, maps to chromosome 8p21. Fine structure in situ mapping showed that NKX3.1 is proximal to MSR32 (macrophage scavenger receptor type II) and LPL (human lipoprotein lipase) and very close to NEFL (human neurofilament light chain) on 8p21. Single-strand conformational polymorphism analysis of 48 radical prostatectomy cancer specimens and 3 metastases for the entire coding region of NKX3.1 showed no tumor-specific sequence alterations in 50 specimens and total absence of the gene in 1 specimen known to have a biallelic deletion of 8p21. NKX3.1 was found to have a polymorphism at nucleotide 154 in codon 52 that resulted in a CGC-->TGC sequence change and an Arg-->Cys amino acid alteration (R52C). This polymorphism was present in 20% of DNA samples. If NKX3.1 is a target of the 8p21 LOH, it is not via disruption of the coding region of the gene.
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PMID:Coding region of NKX3.1, a prostate-specific homeobox gene on 8p21, is not mutated in human prostate cancers. 937 51

Although the differentiation of mature osteoblasts has been well studied, there is still a need for a convenient way to study preosteoblast differentiation. Our laboratory has recently described a method for isolating small numbers of authentic osteoblast precursor cells from human bone marrow (Rickard et al., J Bone Miner Res 11:312-324, 1996). Here we describe the conditional immortalization of these cells by retroviral transfection with the amphotrophic vector, pZipSV40tsa58, which encodes for a temperature-sensitive mutant form of the simian virus large T-antigen. At the permissive temperature of 34 degrees C, the cell lines proliferated, but differentiation was arrested, whereas at the restrictive temperature of 39.5 degrees C, proliferation was decreased and differentiation was induced. As assessed by semiquantitative reverse transcriptase PCR after 4 days of culture at 39.5 degrees C, the six cell lines expressed similar mRNA levels both constitutively and in response to dexamethasone (Dex) and 1alpha,25-dihydroxyvitamin D3 (1,25(OH2)D3) for osteoblast (alkaline phosphatase [ALP], type I collagen [Col I], osteocalcin [OC], and parathyroid hormone receptor [PTH-R] and adipocyte (lipoprotein lipase [LPL]) genes. In the presence of 10(-8) M Dex, gene expression for ALP, PTH-R, and LPL increased, but that for OC decreased. Stimulation with 10(-8) M 1,25(OH2)D3 increased gene expression for ALP, OC, and Col I. Changes in protein production for ALP, OC, and type I procollagen in response to Dex and 1,25(OH2)D3 were similar to changes in mRNA levels. When cultured at 39.5 degrees C with ascorbate and beta1-glycerolphosphate for 21 days, mineralization of matrix occurred, whereas culture with Dex plus 1,25(OH2)D3, or rabbit serum led to enhanced formation of cytoplasmic lipid droplets within 6 days. Thus, these cell lines are capable of bipotential differentiation and should serve as an excellent tool to study the molecular mechanisms that regulate and select for osteoblast and adipocyte differentiation in humans.
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PMID:Development and characterization of conditionally immortalized osteoblast precursor cell lines from human bone marrow stroma. 949 13

We cloned and sequenced the -976bp promoter of the rat lipoprotein lipase LPL gene. The sequence was compared with the mouse and human sequences. The homology between the rat and mouse LPL nucleotide sequences was not quite as strong in the promoter sequence as in the coding sequence. Among the 976nt promoter there were 118 divergences, i.e. 11.8%, compared to only 5.6% for the LPL coding region. However, within the 200nt immediately 5' to the transcriptional start site (proximal promoter), the divergence was only 4%. New potential cis-elements (such as CACCC, GATA, GC and GA boxes, IRS, Krox, MEF 2, E-box, CCArGG and 1/2 VDRE) were identified in the rat, mouse or human LPL gene.
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PMID:Cloning, sequencing and structural analysis of 976 base pairs of the promoter sequence for the rat lipoprotein lipase gene. Comparison with the mouse and human sequences. 952 12


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