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)

The hydrolysis of an emulsified triglyceride substrate by clearing factor lipase (lipoprotein lipase) normally requires the presence of particular activating polypeptide species. These are present in serum, together with other inhibitory species, as part of the serum lipoproteins. The paper describes a method whereby the net activating ability of individual human sera may be measured routinely. In a normal population, this activating ability is shown to be correlated positively with the fasting serum triglyceride concentration. As the fasting triglyceride concentration increases, there is a rise in the proportion of the total activating ability that is associated with the very low density lipoproteins. A dietary fat load does not raise the total activating ability but does increase the proportion of the total that is associated with the serum lipoproteins of lowest density.
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PMID:Clearing factor lipase (lipoprotein lipase) activator. A method for the measurement of the net activating ability of human sera. 18 2

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 present study describes a simple method for the purification of bovine milk lipoprotein lipase based on affinity chromatography on agarose containing covalently linked heparin and the use of a non-ionic detergent, Triton X-100. By this procedure miligram amounts of detergent-free lipoprotein-ionic lipase with a specific activity of 28.9 mmoles free fatty acid/mg protein/mg protein/hour can be obtained. The apparent molecular weight of the polypeptide as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate is 55,000. The purified triacylglycerol lipase also hydrolyzes monoacylglycerol, but the activity against this lipid is 40 times lower than that against triacylglycerol.
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PMID:Purification of bovine milk lipoprotein lipase with the aid of detergent. 89 17

In this study, we have characterized the biochemical nature of interleukin (IL)-11 receptors (IL-11R) and determined the possible signal transduction pathways mediated by IL-11 in 3T3-L1 mouse preadipocytes. The results show that IL-11 strongly inhibited lipoprotein lipase activity and adipogenesis in 3T3-L1 cells, and the suppression of lipoprotein lipase activity by IL-11 was controlled at the post-transcriptional level. The ability of IL-11 to inhibit lipoprotein lipase activity and adipogenesis therefore reflected the expression of functional IL-11R on the cell surface. Scatchard plot analysis according to specific binding data revealed the existence of a single class of high affinity IL-11R with a Kd of 3.49 x 10(-10) M and a receptor density of 5140 sites/cell on 3T3-L1 cells. Affinity cross-linking studies with 125I-IL-11 indicated that IL-11R consists of a single polypeptide chain of 151 kDa in size. Furthermore, we have studied the role of protein tyrosine phosphorylation in the IL-11R-linked signal transduction pathways. The results show that IL-11R ligation rapidly and transiently stimulated tyrosine phosphorylation of 152-, 94-, 47-, and 44-kDa proteins. This effect is specific for IL-11 since neutralizing antibody to IL-11 abrogated IL-11-induced tyrosine phosphorylation, and other cytokines such as IL-6 and IL-1 alpha did not change the tyrosine phosphorylation pattern in 3T3-L1 cells. These results suggest that IL-11R is closely linked to a functional protein-tyrosine kinase pathway, and tyrosine phosphorylation may be a key step in the initiation of the IL-11R-mediated transmembrane signaling.
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PMID:Characterization of interleukin-11 receptor and protein tyrosine phosphorylation induced by interleukin-11 in mouse 3T3-L1 cells. 137 23

The hyperplastic capacity of adipose tissue resides in a group of fibroblast-like adipocyte precursor cells. There is evidence to suggest that their proliferation and differentiation is regulated by insulin-like growth factor-I (IGF-I) and transforming growth factor-beta (TGF-beta) but there is less information about other growth factors which may also participate in adipocyte precursor cell hyperplasia. Transforming growth factor-alpha (TGF-alpha) is a 50 amino acid polypeptide which has been shown to stimulate proliferation in both neoplastic and normal cell types acting through the epidermal growth factor (EGF) receptor. We have studied the regulation of DNA synthesis and the activity of lipoprotein lipase by TGF-alpha in chicken adipocyte precursor cells in vitro. Both TGF-alpha and EGF stimulated incorporation of [3H]thymidine into DNA in a dose-dependent manner. TGF-alpha was approximately 180-fold more potent than EGF. Addition of TGF-alpha in combination with IGF-I, TGF-beta 1 or platelet-derived growth factor produced a synergistic increase in DNA synthesis. Short-term incubation with TGF-alpha reduced lipoprotein lipase activity by 23%. These results show that TGF-alpha is a potent mitogen in these adipocyte precursor cells and can inhibit their differentiation in vitro and may participate in the regulation of adipose tissue development in vivo.
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PMID:Effects of transforming growth factor-alpha on chicken adipocyte precursor cells in vitro. 140 26

In this study we have examined effects of synthetic polypeptide fragments of apoC-III on the kinetic properties of lipoprotein lipase (LPL) activity. Based on the loss of 79% of LPL-inhibitory activity after CNBr cleavage at the N-terminal portion of apoC-III and a systematic search for synthetic peptides with LPL-inhibitory activity spanning the apoC-III sequence, we concluded that the N-terminal domain is the most important in the modulation of LPL activity. In addition, there are multiple attachment sites in apoC-III for its interaction with LPL and these sites reside in the hydrophilic sequences of apoC-III. Probably for this reason the intact apo-CIII exhibited higher inhibitory potential than its peptide components. Based on the deduced inhibition constants derived for the synthetic apoC-III1-79 we concluded that apoC-III is likely to exhibit a physiological role in regulating LPL activity since the derived dissociation constants for the LPL-apoC-III interaction are within the physiological concentration range of plasma apoC-III. In addition, as the synthetic apoC-III1-79 lacks the carbohydrate moiety, we also concluded that the presence of the oligosaccharide in native apoC-III is not essential for its inhibitory activity on LPL. The fact that the I50 (concentration for inhibition of LPL at 50% activity) decreases for apoC-III-1 when assayed in the presence of apoC-II indicated that the activator actually caused an increased affinity between LPL and apoC-III and demonstrated that apoC-III does not compete for the activator site of apoC-II.
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PMID:Inhibition of lipoprotein lipase activity by synthetic peptides of apolipoprotein C-III. 143 91

The thiazolidinediones are a class of novel antidiabetic compounds that enhance the response of target tissues to insulin. Pioglitazone, a thiazolidinedione analog, lowers blood glucose and insulin levels in rodent models of non-insulin-dependent diabetes mellitus. We have studied the effect of pioglitazone on 3T3-L1 cells, a cell line that undergoes differentiation from a preadipocyte fibroblastic morphology to that of an adipocyte. Pioglitazone treatment of preadipocytes enhanced the insulin- or insulin-like growth factor-1 (IGF-I)-regulated differentiation (monitored by the rate of lipogenesis or triglyceride accumulation), whereas treatment of the cells in the absence of insulin or IGF-I resulted in no apparent change in the cellular phenotype. Pioglitazone caused both a leftward shift and enhanced maximum response for the IGF-I-regulated differentiation of the cells, consistent with the idea that the drug enhances the sensitivity of cells to polypeptide hormones. A series of pioglitazone analogs were tested in this system, and variations in activity relative to that of the parent compound were observed. A study of the time required for the drug to exert an effect on differentiation revealed that an increased rate of lipogenesis occurred 16-24 hr after drug treatment in appropriately staged cells. An increased rate of glucose transport and increased activity of lipogenic enzymes were noted in a time frame that correlated with the change in lipogenesis. Analysis of mRNA abundance for Glut-4, lipoprotein lipase, and glucose-6-phosphate dehydrogenase showed that pioglitazone enhanced the insulin induction of these mRNA species. Thus, pioglitazone, in combination with insulin or IGF-I, appears to be exerting effects on the cellular phenotype by eliciting changes in the expression of genes that regulate metabolic pathways leading to the acquisition of the differentiated phenotype.
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PMID:Enhancement of adipocyte differentiation by an insulin-sensitizing agent. 153 16

A molecular model of human pancreatic lipase (Winkler, F. K., D'Arcy, A., and Hunziker, W. (1990) Nature 343, 771-774) is used to explain the possible structural effects of the amino acid mutations identified to date in the human lipoprotein and hepatic lipase genes. A sequence homology profile was used to evaluate the alignment of the amino acid sequences of all three lipolytic enzymes (Kirchgessner, T. G., Chuat, J.-C., Heinzmann, C., Etienne, J., Guilhot, S., Svenson, K., Ameis, D., Pilon, C., D'Auriol, L., Andalibi, A., Schotz, M. C., Galibert, F., and Lusis, A. J. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 9647-9651) with respect to the secondary structure elements identified in the pancreatic lipase. As expected, maximum homology is observed in internal regions namely the hydrophobic strands of the central beta-pleated sheet. This observation strongly supports the hypothesis that all three molecules exhibit a very similar three-dimensional structure, particularly in the N-terminal catalytic domain. There is considerable variation in some of the surface loops connecting the individual strands, whereas others are conserved. It is hypothesized that the most conserved loops located around the active site are responsible for the catalytic function (similar for all three enzymes), whereas those that markedly differ are involved in the regulation at the molecular level, namely the binding of colipase (pancreatic enzyme) and apolipoprotein CII (lipoprotein lipase). The currently available library of hepatic and lipoprotein gene mutations seems to indicate that the majority of mutants disrupt the folding of the polypeptide chain, rather than affect specific constellations in and around the catalytic site or regulatory loops.
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PMID:Effects of gene mutations in lipoprotein and hepatic lipases as interpreted by a molecular model of the pancreatic triglyceride lipase. 174 9

Apolipoprotein (apo) E, a major protein component of plasma lipoproteins, is a physiological ligand for the low density lipoprotein (LDL) receptor as well as for a specific apoE receptor; it is therefore an important modulator of lipoprotein metabolism. In this study we cloned and sequenced bovine apoE complementary DNA. Comparison of nucleotide substitution rates shows that apoE is less conservative than apoA-I and evolves about 30% faster than an average mammalian protein. Although apoE is not a conservative protein, several regions have been well conserved among all eight mammalian sequences now available. These include a 33-amino-acid block immediately upsteam from the third intron/exon junction and the LDL receptor binding region. We have also compared published apoC-I and apoC-II sequences. Both proteins are less conservative than apoE. In particular, apoC-I shows no well-conserved region except for a small region in the common 33-amino-acid block, suggesting that the function of apoC-I does not have stringent structural requirements. On the other hand, in apoC-II the region encoded by exon 4, which consists of the last 29 amino acids of the polypeptide, has been rather well conserved, probably because this region is important for the activation of lipoprotein lipase and chylomicron and very low density lipoprotein metabolism.
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PMID:Cloning and sequencing of bovine apolipoprotein E complementary DNA and molecular evolution of apolipoproteins E, C-I, and C-II. 190 18

The notion that a single hormone may exert a broad range of effects has become well established. As such, leukemia inhibitory factor (LIF) is a prime example. LIF was initially described, purified, and genetically cloned on the basis of its ability to induce the differentiation and suppress the clonogenicity of the monocytic leukemia cell line, M1. Subsequently, it has become apparent that in vitro LIF inhibits the differentiation of pluripotential ES cells, stimulates the synthesis of hepatic acute-phase proteins, induces a switch in neurotransmitter phenotype from adrenergic to cholinergic, suppresses adipocyte lipoprotein lipase activity, and results in an increase in bone resorption. Moreover, elevation of LIF levels in vivo has a number of patho-physiological consequences, many of which parallel those effects observed in vitro. The challenge that lies ahead is to determine whether other sites of LIF action exist and to define more clearly the physiological role LIF plays in vivo. A major mechanism of cell-cell communication is by the production and secretion of polypeptide hormones by one cell type, which act either systemically or locally, via interaction with specific receptors on the surface of responsive cells. Recently, it has become apparent that hormones initially described and named, on the basis of a specific action, in many cases exert a spectrum of effects on a broad range of cell types. Moreover, the effects exerted are often mimicked closely by other hormones. Hormones that act in a pleiotropic manner are, for example, transforming growth factor-beta (TGF-beta), the various fibroblast growth factors (FGFs), interleukin-6 (IL-6), and leukemia inhibitory factor (LIF). This review will focus on the various biological effects ascribed to LIF.
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PMID:Leukemia inhibitory factor: a biological perspective. 190 73


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