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)

Circulating basophils are well established sources of the granule-associated mediator, histamine. The physiological control, however, of histamine release from human basophils is poorly understood. Because histamine may play a role in the transendothelial transport of various compounds, including very low density lipoprotein (VLDL) and its hydrolysis products, we investigated the possibility that VLDL regulates mediator release from basophils. The incubation of VLDL (at physiological concentrations) with basophils (isolated as mixed leukocyte preparations) resulted in a significant release of histamine. Histamine release was dependent on VLDL concentration (half-maximal stimulation occurring at VLDL-protein concentration of 15-20 micrograms/ml), length of incubation (half-maximal release at 5-12 min), temperature (37 degrees C optimum) and required calcium (concentration 0.5-2.0 mM). Furthermore, VLDL-induced histamine release was inhibited by three different mediator-release inhibitors: dimaprit, dibutyryl cAMP and nordihydroguaiaretic acid. Incubation of basophils with LDL or HDL under the same experimental conditions did not result in significant histamine release from basophils. The histamine-secretory response of basophils obtained from different donors varied considerably. Basophils isolated from 28 donors and challenged with 100 micrograms/ml VLDL released 23 +/- 5% of their cellular histamine (mean +/- S.E.; with a range of 0-94%). Desensitization of VLDL-induced histamine release could be accomplished by preincubation of basophils with either VLDL or anti-IgE but not with N-formyl-L-methionyl-L-leucyl-L-phenylalanine. Through the secretion of histamine, a potent vasoactive mediator (and also possibly through granule-associated glycosaminoglycans, stimulants of the enzyme lipoprotein lipase), this novel effect of VLDL may be part of a physiological loop for the regulation of VLDL hydrolysis and lipid transport. This effect of VLDL may also have deleterious consequences, because of the atherogenic properties of histamine.
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PMID:Very low density lipoproteins (VLDL) trigger the release of histamine from human basophils. 243 41

A specific diacylglycerol kinase inhibitor, at a concentration of 10(-5) M, consistently enhanced superoxide generation from human neutrophils stimulated with fMet-Leu-Phe, IgG, heat-aggregated IgG and opsonized zymosan. The concentration-response curve for fMet-Leu-Phe was displaced to the left and the maximum superoxide release was also consistently increased by R59022 whereas the diacylglycerol lipase inhibitor, RHC80267, 10(-5) M, had no significant effect. These results suggest that the diacylglycerol formed after fMet-Leu-Phe stimulation in human neutrophils is metabolized largely by the kinase and not the lipase, which implies that diacylglycerol is not the major source of arachidonate during signal-transduction.
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PMID:The diacylglycerol kinase inhibitor, R59022, enhances the superoxide generation from human neutrophils induced by stimulation of fMet-Leu-Phe, IgG and C3b receptors. 303 76

Addition of a guanine nucleotide analog, guanosine 5'-O-(thiotriphosphate) (GTP gamma S)(1-100 microM) induced release of [3H]arachidonic acid from [3H]arachidonate-prelabeled rabbit neutrophils permeabilized with saponin. The chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced arachidonate release was enhanced by GTP gamma S, Ca2+, or their combination. Ca2+ alone (up to 100 microM) did not effectively stimulate lipid turnover. However, the combination of fMLP plus GTP gamma S elicited greater than additional effects in the presence of resting level of free Ca2+. The addition of 100 microM of GTP gamma S reduced the Ca2+ requirement for arachidonic acid liberation induced by fMLP. Pretreatment of neutrophils with pertussis toxin resulted in the abolition of arachidonate release and diacylglycerol formation. Neomycin (1 mM) caused no significant reduction of arachidonate release. In contrast, about 40% of GTP gamma S-induced arachidonate release was inhibited by a diacylglycerol lipase inhibitor, RHC 80267 (30 microM). These observations indicate that liberation of arachidonic acid is mediated by phospholipase A2 and also by phospholipase C/diacylglycerol lipase pathways. Fluoride, which bypasses the receptor and directly activates G proteins, induced arachidonic acid release and diacylglycerol formation. The fluoride-induced arachidonate release also appeared to be mediated by these two pathways. The loss of [3H]arachidonate was seen in phosphatidylinositol, phosphatidylcholine, and phosphatidylethanolamine. These data indicate that a G protein is involved between the binding of fMLP to its receptor and activation of phospholipase A2, and also that the arachidonic acid release is mediated by both phospholipase A2 and phospholipase C/diacylglycerol lipase.
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PMID:Stimulation of arachidonic acid release by guanine nucleotide in saponin-permeabilized neutrophils: evidence for involvement of GTP-binding protein in phospholipase A2 activation. 312 72

Bovine milk lipoprotein lipase was subjected to amino acid sequence analysis. The first 19 amino-terminal residues were Asp-Arg-Ile-Thr-Gly-Gly-Lys-Asp-Phe-Arg-Asp-Ile-Glu-Ser-Lys-Phe-Ala-Leu- Arg. In addition, reversed-phase high-performance liquid chromatography of a tryptic digest of reduced and alkylated lipase resolved a number of peptides, five of which contained cysteine. Sequence analysis of the tryptic peptides revealed in most instances a close homology to porcine pancreatic lipase. Based on this homology, the relative alignment of the sequenced lipoprotein lipase peptides can be made. In addition, a potential binding site for the triacylglycerol substrate and a carbohydrate-binding domain for lipoprotein lipase are postulated.
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PMID:Homology of lipoprotein lipase to pancreatic lipase. 345 70

Lipoprotein lipase from bovine milk reacted stoichiometrically with diisopropylphosphorofluoridate (DFP), an inactivator of serine esterases, resulting in the loss of enzymatic activity against triacylglycerols. The reaction obeyed first-order kinetics with a rate constant of 0.69 h-1. In order to isolate the peptide containing the diisopropylphosphoryl moiety (DIP), partially purified lipoprotein lipase was covalently labeled with [3H]DFP, and the labeled protein was reduced, carboxymethylated, and further purified to about 90% homogeneity. Cyanogen bromide cleavage followed by gel filtration yielded a radioactive peptide of 6-8 kDa. This peptide was succinylated and then digested with Staphylococcus aureus V8 proteinase. From this digest, a peptide containing 0.95 mol of [3H] DIP/mol of peptide was isolated by gel-permeation chromatography followed by reverse-phase high performance liquid chromatography. Automated Edman degradation provided the following sequence: Ala-Ile-Gly-Ile-His-Trp-Gly-Gly- (DIP)Ser-Pro-Asn-Gln-Lys-Asn-Gly-Ala-Val-Phe-Ile-Asn-(Ser, Leu)-Glu. Analysis of the sequence for secondary structure suggests that the reactive serine of lipoprotein lipase is in a beta-turn, a structure similar to those of the active sites of most other serine proteinases. Lipoprotein lipase appears to share this secondary structure with other serine hydrolases despite significant differences in the primary structure of this domain.
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PMID:Isolation of an active-site peptide of lipoprotein lipase from bovine milk and determination of its amino acid sequence. 352 32

The effects of chronic ethanol consumption on lactational performance were studied in the rat on day 15 after delivery by determining mammary gland and milk composition, while growth rate and metabolic parameters were studied in pups coming from untreated mothers but being suckled by ethanol-treated mothers. Alcohol treatment increases the dry weight and lipoprotein lipase activity in the mammary gland, and decreases both absolute and relative mammary gland weight and mammary tissue protein content. The triacylglycerol concentration of milk from treated dams is increased, whereas lactose concentration is decreased in comparison to milk from controls, although the total energy content of milk from alcohol-treated dams is higher than that from controls. Ethanol treatment produces a reduction of daily milk production. Pups nursed by alcoholic mothers show a retarded growth with respect to pups nursed by untreated mothers. Furthermore, they present a reduction in the levels of circulating glucose, insulin, glycerol and free fatty acids, whereas an increase in acetoacetate and in urea levels is observed. Pups from alcoholic mothers show reduced glycogen concentration in the liver while the protein content is increased. Plasma free amino acids in pups nursed by alcoholic mothers are lower than in control pups, the differences in Ala, Glu+Gln, Gly, Pro, 4-OH-Pro, citrulline, Cys, Tyr, Phe and the combined total values being statistically significant. We may therefore draw the conclusion that chronic ethanol treatment impairs lactational performance affecting mammary gland function as shown by the decline in milk production and altered milk composition.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of chronic ethanol consumption on lactational performance in rat: mammary gland and milk composition and pups' growth and metabolism. 362 48

Administration of BRL 26314 [N-(4-chlorobenzyl)-L-phenylalanine] raises circulating high-density lipoprotein (HDL) cholesterol and lowers total triglyceride levels in rats whether maintained on stock or semi-synthetic diets. HDL is also elevated by BRL 26314 in hypothyroid rats and in rats with pre-existing hyperlipidaemia where aortic total cholesterol concentration is decreased. BRL 26314 promotes the excretion of a dose of radiolabelled cholesterol as faecal sterols and bile acids, and decreases the extent of cholesterol-radiolabelling in tissue pools, particularly the aorta and adipose tissue. The increase in cholesterol and bile acid (cholic acid) turnover distinguishes BRL 26314 from a cholestatic agent such as 1-naphthyl isothiocyanate where a superficially similar change in HDL concentration disguises an impaired cholesterol transport. BRL 26314 is not a general protein inducer but part of the mechanism of action may involve enhancement of white adipose tissue lipoprotein lipase activity.
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PMID:Hyperalphalipoproteinaemic activity of BRL 26314--I. Enhanced cholesterol turnover in rats. 654 91

Class A amphipathic helical peptides have been shown to mimic many properties of exchangeable apolipoproteins. The three analogs of the class A amphipathic peptides were used to probe the structure and function of human very low density lipoproteins (VLDL): 1) 18 residue peptide possessing a single helical domain (18A) with the sequence Asp-Trp-Leu-Lys-Ala-Phe-Tyr-Asp-Lys-Val-Ala-Glu-Lys-Leu-Lys-Glu-Ala-Phe; 2) two domains of 18A separated by a Pro (37pA); and 3) and 18A analog with the end groups protected to increase helicity (Ac-18A-NH2). Upon incubation of the peptides with VLDL at a peptide to VLDL, (protein) ratio of 1:1, the 37pA and Ac-18A-NH2 were able to displace most of apolipoprotein (apo) Cs and E from VLDL without alteration in its lipid composition and morphology while 18A had minimal effect. The extent of displacement was a function of the peptide to VLDL ratio. The rank order of displaceability of apolipoproteins on VLDL was apoE > C-III > C-II. The displacement of apoE and/or Cs from VLDL by peptides variably affected the ability of VLDL to interact with purified bovine milk lipoprotein lipase (LpL) and cultured macrophages. Treatment of VLDL with Ac-18A-NH2 markedly lowered its reactivity to LpL and its ability to induce lipid accumulation in cultured macrophages: however, treatment of VLDL with 37pA or 18A only minimally lowered their abilities. Ac-18A-NH2 treatment of VLDL resulted in the increase of apparent K(m) and a decrease of Vmax for lipoprotein lipase (LpL)-catalyzed hydrolysis of VLDL triglycerides. When an artificial triglyceride emulsion was used as a substrate of LpL, 37pA, but not Ac-18A-NH2, activated LpL. The above data indicate that 1) amphipathic helical peptides can alter the metabolic and functional properties of VLDL by dissociating the functionally important exchangeable apolipoproteins from VLDL as well as by acting as a functional element of VLDL after their incorporation; and 2) the class A amphipathic peptides having different lipid-associating properties exert significantly different effect on VLDL function.
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PMID:Probing structure and function of VLDL by synthetic amphipathic helical peptides. 872 61

When rat polymorphonuclear neutrophils (PMN) were treated with N-formyl-Met-Leu-Phe (fMLP), the release of arachidonic acid in preference to other fatty acids was observed. Levels of arachidonic acid reached a plateau within 5 min, and were accompanied by an approximately 4-fold increase in in vitro phospholipase (PL) A2 and PLD activities in PMN lysates. Treatment of PMN with ethanol (an inhibitor of PLD-mediated phosphatidic acid formation), propranolol (a phosphatidic acid phosphatase inhibitor), or 4-bromophenacylbromide (a PLA2 inhibitor), each suppressed fMLP-stimulated arachidonate release. Treatment with RHC-80267 (a diacylglycerol lipase inhibitor), however, had no such effect. The cytosolic PLA2 (cPLA2) inhibitor, arachidonoyl trifluoromethyl ketone, suppressed PLA2 activity in PMN homogenates and arachidonate release by fMLP-treated PMN. These results suggest that fMLP-elicited arachidonate release is mediated by cPLA2 but not diacylglycerol lipase, and that the activation of cPLA2 is downstream of the PLD-dependent signaling pathway.
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PMID:Phospholipase D is involved in cytosolic phospholipase A2-dependent selective release of arachidonic acid by fMLP-stimulated rat neutrophils. 889 14

We have shown previously that the stem cell factor (SCF) receptor undergoes phosphorylation on serine residues following ligand stimulation, and that this phopshorylation is dependent mainly on the activity of protein kinase C (PKC). In the present study, we have further investigated the molecular mechanisms behind SCF-stimulated activation of PKC, and found that SCF does not activate phosphatidylinositol-specific phospholipase C. In contrast, phospholipase D (PLD) is activated in response to SCF in a dose-dependent manner. Activation of PLD was not inhibited by calphostin C, an inhibitor of PKC. On the other hand, inhibitors of phosphatidylinositol PtdIns 3'-kinase (PtdIns 3'-kinase), i.e. wortmannin and LY294002, inhibited SCF-induced PLD activation. Moreover, a mutant SCF receptor in which Tyr721, which is responsible for activation of PtdIns 3'-kinase, is mutated to a phenylalanine residue was unable to mediate activation of PLD. Thus, PtdIns 3'-kinase appears to be essential for SCF-induced PLD activation. Furthermore, we demonstrate that phosphatidic acid (PtdH), generated through the action of PLD in response to SCF, is metabolized to diacylglycerol by dephosphorylation. Diacylglycerol can then activate PKC, and, moreover, after deacylation by a diacylglycerol lipase, yield arachidonic acid, an important second messenger in cell signaling.
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PMID:Involvement of phosphatidylinositol 3'-kinase in stem-cell-factor-induced phospholipase D activation and arachidonic acid release. 931 Mar 72


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