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)

Extracts of acetone-ether powders of bovine thoracic aorta contain lipase activity which has an alkaline pH maximum (7.8-8.4) and is stimulated 4-10-fold by adding serum or isolated apolipoprotein-glutamate to the assay mixture. Serum activation is completely reversed by isolated apolipoprotein-serine or apolipoprotein-alanine. Lipolysis is strongly inhibited by NaCl (0.5 M) and protamine sulfate (1 mg/ml) and partially inhibited by heparin. Based on these characteristics, the lipase is identified as lipoprotein lipase.
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PMID:Detection and partial characterization of lipoprotein lipase in bovine aorta. 0 Oct 87

We have recently shown that glutamate exerts a stimulatory action on somatostatin secretion in cortical neurons essentially through NMDA receptor sites. Here, we investigated whether arachidonic acid release could be modified after NMDA receptor activation in cortical neurons in primary culture. We also studied whether pharmacological manipulation of phospholipase A2 could modify somatostatin release. We found that both glutamate and NMDA (N-methyl-D-aspartate) stimulated [3H]arachidonic acid release. NMDA-evoked arachidonic acid release was inhibited by MK-801 and TCP (two NMDA receptor-type antagonists), or by mepacrine, an inhibitor of phospholipase A2. NMDA-induced somatostatin release was inhibited by MK-801, mepacrine and by another phospholipase A2 inhibitor, p-bromophenacylbromide (pBPB). However, responses to NMDA were unaffected by H7, NDGA (nordihydroguaiaretic acid), indomethacin or by RHC 80267 (inhibitors of protein kinase C, lipooxygenase, cyclooxygenase and diacylglycerol lipase, respectively). Mepacrine (greater than or equal to 100 microM) decreased NMDA-stimulated phosphatidylinositol (PI) hydrolysis and at higher concentrations (250 microM) was also able to inhibit basal release whereas pBPB had no effect in the range of concentrations tested. Neomycin (which inhibits phosphatidylinositol metabolism by binding strongly and selectively to inositol phospholipids) reduced by 30% the NMDA-stimulated somatostatin release, although chronic treatment of neurons with the phorbol ester 12-myristate, 13-acetate (PMA) had no effect on this response. Melittin, an activator of phospholipase A2, was able to stimulate both arachidonic acid release and somatostatin secretion. High-performance liquid chromatography (HPLC) analysis of tritiated metabolites released from cortical neurons under basal or NMDA-stimulated conditions revealed that [3H]arachidonic acid was the only metabolite detectable. Furthermore, external addition of arachidonic acid increased somatostatin secretion. Our results show a correlation between the two parameters studied.
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PMID:NMDA receptor activation stimulates phospholipase A2 and somatostatin release from rat cortical neurons in primary cultures. 135 46

In primary cultures of cerebellar granule cells, glutamate, aspartate, and N-methyl-D-aspartate (NMDA) induced a dose-dependent release of [3H]arachidonic acid ([3H]AA) which was selective for these agonists and was inhibited by NMDA receptor antagonists. The agonist-induced [3H]AA release was reduced by quinacrine at concentrations that inhibited phospholipase A2 (PLA2) but affected neither the activity of phospholipase C (PLC) nor the hydrolysis of phosphoinositides induced by glutamate or quisqualate. Thus, the increased formation of AA was due to the receptor-mediated activation of PLA2 rather than to the action of PLC followed by diacylglycerol lipase. The receptor-mediated [3H]AA release was dependent on the presence of extracellular Ca2+ and was mimicked by the Ca2+ ionophore ionomycin. Pretreatment of granule cells with either pertussis or cholera toxin failed to inhibit the receptor-mediated [3H]AA release. Hence, in cerebellar granule cells, the stimulation of NMDA-sensitive glutamate receptors leads to the activation of PLA2 that is mediated by Ca2+ ions entering through the cationic channels functioning as effectors of NMDA receptors. A coupling through a toxin-sensitive GTP-binding protein can be excluded.
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PMID:N-methyl-D-aspartate-sensitive glutamate receptors induce calcium-mediated arachidonic acid release in primary cultures of cerebellar granule cells. 217 63

The concentrations of ATP and the ATP/AMP concentration ratios were maintained in thioglycollate-elicited mouse peritoneal macrophages incubated in vitro for 90 min in the presence or absence of added substrate: rates of glycolysis, lactate formation and glutamine utilization were approximately linear with time for at least 60 min of incubation. The rate of oxygen consumption by macrophages was only increased above the basal rate (i.e. that in the absence of added substrate) by addition of succinate or pyruvate, or by addition of the uncoupling agent carboxyl cyanide m-chlorophenylhydrazone ('CCCP'); it was decreased by 75% by the addition of KCN. These findings suggest that metabolism of endogenous substrate can provide most, if not all, of the energy requirement of these cells, at least for a short period. The rates of glucose and glutamine utilization by incubated macrophages were approx. 300 and 100 nmol/min per mg of protein respectively. A large proportion of the glutamine that is utilized is converted into glutamate and aspartate, and very little (perhaps less than 10%) is oxidized. Similarly almost all of the glucose that is utilized is converted into lactate and very little is oxidized. This characteristic is similar to that of resting lymphocytes and rapidly dividing cells; in non-proliferating macrophages it may be a mechanism to provide precision in control of the rate of biosynthetic processes that utilize intermediates of these pathways, e.g. purines and pyrimidines for mRNA for the synthesis of secretory proteins and glycerol 3-phosphate for phospholipid synthesis for membrane recycling. No utilization of acetoacetate or 3-hydroxybutyrate by macrophages was detected. In contrast, both butyrate and oleate were oxidized. The rate of [14C]oleate conversion into 14CO2 (1.3 nmol/h per mg of protein) could account for most of the oxygen consumption by incubated macrophages, suggesting that long-chain fatty acids might provide an important fuel in situ. This may be one explanation for the secretion of lipoprotein lipase by these cells, to provide fatty acids for oxidation from the degradation of local triacylglycerol.
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PMID:Rates of utilization and fates of glucose, glutamine, pyruvate, fatty acids and ketone bodies by mouse macrophages. 359 69

1. The effects of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD), a non-selective agonist of the metabotropic glutamate receptors (mGluRs), have been studied in rat cortical and striatal slices by measuring the depolarization-induced output of D-[3H]-aspartate (D-[3H]-Asp) and of [3H]-glutamate ([3H]-Glu), neosynthesized from [3H]-glutamine. 2. In cortical slices, 1S,3R-ACPD potentiated the depolarization-induced (KCl, 30 mM) output of both D-[3H]-Asp and [3H]-Glu. The potentiation, obtained at 300 microM 1S,3R-ACPD was 65 +/- 6% for D-[3H]-Asp and 56 +/- 10% for [3H]-Glu. Conversely, in striatal slices, 1S,3R-ACPD reduced the depolarization-induced transmitter output. The reduction, obtained at 300 microM of the agonist, was 60 +/- 8% for D-[3H]-Asp and 50 +/- 5% for neosynthesized [3H]-Glu. 3. Bovine serum albumin (BSA, 15 microM), which is able to bind locally produced fatty acids, completely eliminated the potentiating effect 1S,3R-ACPD had on D-[3H]-Asp output from cortical slices. Low concentrations of arachidonic acid (1-10 microM) or of oleic acid (1-10 microM) added to BSA-containing perfusion medium, restored this potentiating effect. BSA, however, had no effect on the inhibitory action of 1S,3R-ACPD in striatal slices. 4. Bromophenacyl bromide (100 microM), an inhibitor of phospholipase A2, and RG80267 (100 microM), an inhibitor of diacylglycerol lipase, have been shown to inhibit fatty acid production. These compounds prevented the potentiating effect of 1S,3R-ACPD on D-[3H]-Asp-output in cortical slices. 5. Indomethacin (100 microM), an inhibitor of cyclo-oxygenases, plus nordihydroguaiaretic acid (100 microM), an inhibitor of lipoxygenases, increased D-[3H]-Asp output in cortical slices perfused with BSA-containing medium. 6. These experiments suggest that the mGluR-mediated potentiation of transmitter output requires the availability of unsaturated fatty acids, such as arachidonic or oleic acids, in cortical slices. In contrast, the mGluR-induced inhibition of transmitter output is not dependent upon fatty acid availability in striatal slices. The requirement of both unsaturated fatty acids and 1S,3R-ACPD in the facilitation of transmitter exocytosis may play an important role in the regulation of synaptic plasticity.
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PMID:Metabotropic glutamate receptors, transmitter output and fatty acids: studies in rat brain slices. 882 62

The contributions of several Ca(2+)-dependent processes to neurotoxicity were examined in primary cultures of rat cortical neurons. The Ca2+ ionophore ionomycin induced a rapid loss of axonal morphology and concomitant release of inositol phosphates that preceded morphological alterations of neuronal cell bodies, choline and arachidonate release, and protein degradation. These events were followed by a degree of neuronal lysis proportional to the external Ca2+ concentration and exposure time. The phospholipase inhibitor neomycin decreased both arachidonate release and the phospholipid hydrolysis catalysed by phospholipases C and D. Proteolysis was abated by the protease inhibitor leupeptin, but not by lysosomal proteolysis inhibitors. Neuronal lysis was inhibited partially by either leupeptin or neomycin and almost completely by both in combination. However, neither agent, alone or in combination, affected the morphological derangements. The diacylglycerol lipase inhibitor RHC-80267 reduced arachidonate release, but not neuronal lysis. Phospholipase A2 inhibitors had no effect on either arachidonate release or lysis. Treatment of mixed cultures of neurons and glia with a Ca(2+)-dependent glutamate challenge caused similar morphological changes and a delayed neuronal lysis that was also diminished by leupeptin and neomycin, but not by inhibitors of lysosomal proteolysis. These data describe several distinct stages of Ca(2+)-dependent injury to cortical neurons, a key feature of which is the stimulation of protease, and phospholipase C and D activities. The initial stage is characterized by a rapid loss of axonal morphology and increased phosphatidylinositol hydrolysis. An intermediate stage involves changes in cell body morphology plus the degradation of neuronal protein and phosphatidylcholine. In a later stage, the loss of plasma membrane integrity denotes neuronal death.
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PMID:Ca(2+)-dependent mechanisms of cell injury in cultured cortical neurons. 969 20

Apolipoprotein CII (apoCII) activates lipoprotein lipase (LPL). Seven residues, located on one face of a model alpha-helix spanning residues 59-75, are fully conserved in apoCII from ten different animal species. We have mutated these residues one by one. Substitution of Ala(59) by glycine, or Thr(62) and Gly(65) by alanine did not change the activation, indicating that these residues are outside the LPL-binding site. Replacement of Tyr(63), Ile(66), Asp(69), or Gln(70) by alanine lowered the affinity for LPL and the catalytic activity of the LPL-apoCII complex. For each residue several additional replacements were made. Most mutants retained some activating ability, but replacement of Tyr(63) by phenylalanine or tryptophan and Gln(70) by glutamate caused almost complete loss of activity. All mutants bound to liposomes with similar affinity as wild-type apoCII, and they also bound with similar affinity to LPL in the absence of hydrolyzable lipids. However, the inactive mutants did not compete with wild-type apoCII in the activation assay. Therefore, we conclude that the productive apoCII-LPL interaction may be dependent on substrate molecules. In summary, our data demonstrate that residues 63, 66, 69, and 70 are of special importance for the function of apoCII, but no single amino acid residue is absolutely crucial.
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PMID:Functional analyses of human apolipoprotein CII by site-directed mutagenesis: identification of residues important for activation of lipoprotein lipase. 1171 5

The following areas are discussed in this review: atherogenesis; cerebrovascular factors; hypoperfusion; beta-amyloid production; beta-amyloid fibril formation; beta-sheets; metal cations; reactive oxygen species/free radicals; chronic inflammatory factors; endogenous plasma heparin; lipoprotein lipase; polyamines; protein kinase C; casein kinases; phospholipase A2; serine proteases; myeloperoxidase; cyclooxygenase 2; cysteine proteases; caspases; proprotein convertases; aspartic proteases; cyclin proteinases; thrombin; tau hyperphosphorylation; advanced glycosylation end products; activator protein 1; calcium; apolipoprotein E epsilon4; histamine; blood-brain barrier; glutamate; transglutaminase; insulin-like growth factor 1.
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PMID:Pathogenic factors in vascular dementia and Alzheimer's disease. Multiple actions of heparin that probably are beneficial. 1528 60

Activation of group I metabotropic glutamate (mGlu) receptors drives the endocannabinoid system to cause both short- and long-term changes of synaptic strength in the striatum, hippocampus, and other brain areas. Although there is strong electrophysiological evidence for a role of endocannabinoid release in mGlu receptor-dependent plasticity, the identity of the endocannabinoid transmitter mediating this phenomenon remains undefined. In this study, we show that activation of group I mGlu receptors triggers the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG), but not anandamide, in primary cultures of corticostriatal and hippocampal slices prepared from early postnatal rat brain. Pharmacological studies suggest that 2-AG biosynthesis is initiated by activation of mGlu5 receptors, is catalyzed by phospholipase C (PLC) and 1,2-diacylglycerol lipase (DGL) activities, and is dependent on intracellular Ca2+ ions. Realtime polymerase chain reaction and immunostaining analyses indicate that DGL-beta is the predominant DGL isoform expressed in corticostriatal and hippocampal slices and that this enzyme is highly expressed in striatal neurons, where it is colocalized with PLC-beta1. The results suggest that 2-AG is a primary endocannabinoid mediator of mGlu receptor-dependent neuronal plasticity.
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PMID:Stimulation of endocannabinoid formation in brain slice cultures through activation of group I metabotropic glutamate receptors. 1605 47

Endocannabinoids play central roles in retrograde signaling at a wide variety of synapses throughout the CNS. Although several molecular components of the endocannabinoid system have been identified recently, their precise location and contribution to retrograde synaptic signaling is essentially unknown. Here we show, by using two independent riboprobes, that principal cell populations of the hippocampus express high levels of diacylglycerol lipase alpha (DGL-alpha), the enzyme involved in generation of the endocannabinoid 2-arachidonoyl-glycerol (2-AG). Immunostaining with two independent antibodies against DGL-alpha revealed that this lipase was concentrated in heads of dendritic spines throughout the hippocampal formation. Furthermore, quantification of high-resolution immunoelectron microscopic data showed that this enzyme was highly compartmentalized into a wide perisynaptic annulus around the postsynaptic density of axospinous contacts but did not occur intrasynaptically. On the opposite side of the synapse, the axon terminals forming these excitatory contacts were found to be equipped with presynaptic CB1 cannabinoid receptors. This precise anatomical positioning suggests that 2-AG produced by DGL-alpha on spine heads may be involved in retrograde synaptic signaling at glutamatergic synapses, whereas CB1 receptors located on the afferent terminals are in an ideal position to bind 2-AG and thereby adjust presynaptic glutamate release as a function of postsynaptic activity. We propose that this molecular composition of the endocannabinoid system may be a general feature of most glutamatergic synapses throughout the brain and may contribute to homosynaptic plasticity of excitatory synapses and to heterosynaptic plasticity between excitatory and inhibitory contacts.
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PMID:Molecular composition of the endocannabinoid system at glutamatergic synapses. 1672 19


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