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)

Remodelling of plasma high density lipoproteins (HDL) promotes the dissociation of lipid-free apolipoprotein (apo)A-I from the particles. In the present study, we have investigated the formation of new HDL particles from lipid-free apoA-I in a process dependent on the presence of nonesterified fatty acids (NEFA) and other lipoprotein fractions (as donors of lipid). Incubations were carried out that included lipid-free apoA-I, VLDL, and lipoprotein lipase (LPL) or lipid-free apoA-I, either VLDL or LDL, and sodium oleate. Any new HDL particles that were formed were separated from lipid-free apoA-I in the ultracentrifuge. When any one of the ingredients in the incubation was absent, the apoA-I remained lipid-free; however, when all the ingredients were present, a significant proportion of the apoA-I was recovered in the HDL density fraction. This coincided with the formation of at least three HDL-sized subpopulations; one of the subpopulations was considerably smaller than HDL3c and had pre-beta 1 mobility while two were in the size range of human HDL2b and HDL3c and had pre-beta 2 electrophoretic mobility. The new HDL were predominantly discoidal in shape and their major constituents were apoA-I, phospholipid, and unesterified cholesterol. In conclusion, these results show that lipid-free apoA-I can form new HDL particles in the presence of NEFA and other lipoprotein fractions. The formation of pre-beta 1 HDL from lipid-free apoA-I indicates that this process is potentially of great importance in terms of generating plasma acceptors of cell cholesterol in reverse cholesterol transport.
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PMID:Formation of new HDL particles from lipid-free apolipoprotein A-I. 886 56

We wished to establish whether the haemodynamic changes accompanying alterations in blood pressure exert a direct effect on clearance of chylomicron-like emulsions. N-Nitro-L-arginine (NOLA) and endothelin-1 were used to increase the blood pressure of normotensive rats, sodium nitroprusside (NP) and calcitonin gene-related peptide (CGRP) were used to decrease the blood pressure of spontaneously hypertensive rats (SHR). The lipid emulsions contained radiolabeled triolein (TO) and cholesteryl oleate (CO) to trace plasma clearances. NP and CGRP enhanced TO clearance in the SHR but slowed the rate of CO clearance. NOLA in normotensive rats clearly slowed the rate of TO removal and also retarded CO clearance, whereas with endothelin-1 TO clearance remained unaffected and CO removal was markedly slowed. The effects on TO clearance are consistent with changes in arteriolar resistance regulating access of emulsion particles to lipoprotein lipase on the endothelial cells of capillaries in muscle and adipose tissue. The changes in CO removal rate are more difficult to interpret because factors determining hepatic blood flow are complex. The results suggest that haemodynamic changes potentially affect circulation times of various lipoprotein species in the plasma, with probable consequences in relation to atherogenesis.
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PMID:Vasoactive mediators affect the clearance of lipids from emulsion models of plasma lipoproteins in rats. 890 8

Mechanisms of the stimulatory release of lipoprotein lipase (LPL) activity from isolated rat fat pads by sodium orthovanadate (vanadate) were studied through a cAMP-dependent process. A potent inhibitor of insulin receptor tyrosine kinase, quercetin, inhibited the vanadate-increasing effect on the LPL activity in fat pads, but did not inhibit the vanadate-stimulated release of LPL activity from the fat pads. Propranolol and N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide (H-8) decreased the vanadate-stimulated release in a dose-dependent manner. Isoproterenol and dibutyryl cAMP (Bt2cAMP) stimulated the release of LPL activity from fat pads. Vanadate, as well as isoproterenol, rapidly increased the cAMP content in fat pads, and this increase was almost completely inhibited by propranolol. Vanadate increased the cAMP-dependent protein kinase (PKA) activity ratios calculated from the measurement in the presence or absence of cAMP or PKa inhibitor. These results suggest that the vanadate-stimulated release of LPL activity is associated with a process involving a rapid increase in the cAMP content accompanied by the activation of PKA.
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PMID:Involvement of the rapid increase in cAMP content in the vanadate-stimulated release of lipoprotein lipase activity from rat fat pads. 895 Nov 55

Treatment of aspirinated platelets with the electroneutral K+/H+ exchanger nigericin induces a decrease in intraplatelet pH as measured with the intracellular fluorescent indicator BCECF. Under these conditions, the proton permeability of the plasma membrane is unaffected. The addition of thrombin induces a rapid partial recovery of pH(i), which is completely abolished by the Na+/H+ exchanger inhibitor NHA. The effect is also evident in the presence of the PKC inhibitors GF 109203X or staurosporine and in the absence of both external (EGTA-chelated) and internal (BAPTA-chelated) Ca2+. This makes the thrombin-induced activation of the exchanger independent of the involvement of the hitherto described activators, namely PKC and the increase in [Ca2+]i, as well of the recently reported activator arachidonic acid [Cavallini, L., Coassin, M., Borean, A., and Alexandre, A. (1996) Biochem. J. 319, 567-574], whose production requires a high [Ca2+]i. The thrombin-dependent recovery of pH(i) is prevented by the phospholipase C inhibitor ET 18 O-CH3 and is mimicked by the addition of the permeable diglyceride dioctanoyl glycerol (DiC8) exogenously supplied. The effect of thrombin and DiC8 is unaffected by inhibition of diacylglycerol lipase and diacylglycerol kinase. These experiments identify diglyceride as a novel activator of the Na+/H+ exchanger in platelets.
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PMID:Diacylglycerol mediates the thrombin-induced, protein kinase C and Ca2+ independent activation of the Na+/H+ exchanger in platelets. 900 May 21

Tissue factor pathway inhibitor (TFPI) is a primary regulator of the initiation of blood coagulation. TFPI is internalized and degraded by HepG2 cells through the low-density-lipoprotein receptor-related protein (LRP) but also binds another molecule present on the cell surface at approx. 10-fold the abundance of LRP [Warshawsky, Broze and Schwartz (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 6664-6668]. When HepG2 cells are washed with heparin or dextran sulphate, a substance that binds TFPI is removed from the cell surface and can be detected in a slot-blot assay. Preincubation with trypsin destroys the reactivity of the TFPI-binding component in the slot-blot assay, suggesting that it is a protein. In addition, when the sulphation of glycosaminoglycans (GAGs) is prevented by growing the HepG2 cells in the presence of 30 mM sodium chlorate, TFPI binding is unaffected, whereas the binding of bovine lipoprotein lipase, a protein known to associate with cell-surface GAGs, falls to 50% of control levels. Dextran sulphate washes of HepG2 cells grown in sodium chlorate have an equal reactivity in slot-blot experiments to that of non-treated cells, suggesting that GAGs are not totally responsible for the binding activity observed. By using the slot blot to follow binding activity and conventional protein purification techniques, a protein species that migrates at 40 kDa after reduction was identified in the HepG2 cell wash. The binding of this protein to TFPI was confirmed with immobilized TFPI. Amino acid sequence analysis identified this protein species as a proteolytic fragment of glypican-3 (also called OCI-5), a member of the glypican family of glycosylphosphatidylinositol-anchored proteoglycans.
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PMID:Glypican-3 is a binding protein on the HepG2 cell surface for tissue factor pathway inhibitor. 935 32

In previous studies, we have shown that mouse RAW 264.7 macrophages possess pyrimidinoceptors, coupled to a phosphoinositide-specific phospholipase C, with a higher specificity for UTP than for ATP. In the current study, we explored the mechanism involved in the UTP-induced intracellular acidification seen in this cell line. UTP (30 microM) caused a reversible pHi decrease of 0.16 +/- 0.01 unit; this effect was not influenced by the removal of extracellular Cl- or Na+ ions or by pretreatment with 5-(N-ethyl-N-isopropyl)-amiloride (10 microM), 5-nitro-2-(3-phenylpropylamino)benzoic acid (100 microM), staurosporine (1 microM), or Ro 31-8220 (1 microM) but was completely abolished by the removal of extracellular Ca2+. UTP (30 microM), thapsigargin (1 microM), and ionomycin (1 microM) each induced a similar extent of external Ca2+-dependent acidification with a similar time-dependency, but the effects were nonadditive. To further investigate the Ca2+-dependent mechanism, we studied the involvement of arachidonic acid (AA) and eicosanoid metabolites. The addition of AA (10 microM) but not arachidic acid (100 microM) produced a reduction in pHi. UTP, thapsigargin, and ionomycin induced Ca2+-dependent AA release. Furthermore, 4-bromo-phenacyl bromide [30 microM, a phospholipase A2 (PLA2) inhibitor-, nordihydroguaiaretic acid (50 microM, a lipoxygenase inhibitor), and MK-886 (10 microM, a 5-lipoxygenase-activating protein inhibitor) abolished the UTP- or ionomycin-induced responses, whereas indomethacin (30 microM, a cyclooxygenase inhibitor) and baicalein (10 microM, a selective 12-lipoxygenase inhibitor) had no effect. MAFP (a cPLA2 inhibitor) and REV 5901 (a 5-lipoxygenase inhibitor as well as a competitive antagonist of peptide leukotrienes), but not RHC 80267 (a diacylglycerol lipase inhibitor), also inhibited the UTP-induced response. In contrast, the pHi response to AA was unaffected by the presence of 4-bromo-phenacyl bromide or the removal of extracellular Ca2+ ions but abolished by addition of NDGA. Exogenous 5-hydroperoxyeicosatetraenoic acid (2 microM) also produced marked acidification, and UTP and ionomycin both induced peptide leukotriene formation. In conclusion, this is the first report indicating that lipoxygenase metabolites act as mediators of the Ca2+-dependent acidification seen in macrophages in response to UTP or ionomycin via activation of cPLA2 and AA release.
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PMID:Lipoxygenase metabolites as mediators of UTP-induced intracellular acidification in mouse RAW 264.7 macrophages. 946 90

Cortisol is known to increase whole body lipolysis, yet chronic hypercortisolemia results in increased fat mass. The main aim of the study was to explain these two apparently opposed observations by examining the acute effects of hypercortisolemia on lipolysis in subcutaneous adipose tissue and in the whole body. Six healthy subjects were studied on two occasions. On one occasion hydrocortisone sodium succinate was infused i.v. to induce hypercortisolemia (mean plasma cortisol concentrations, 1500 +/- 100 vs. 335 +/- 25 nmol/L; P < 0.001); on the other occasion (control study) no intervention was made. Lipolysis in the s.c. adipose tissue of the anterior abdominal wall was studied by measurement of arterio-venous differences, and lipolysis in the whole body was studied by constant infusion of [1,2,3-2H5]glycerol for measurement of the systemic glycerol appearance rate. Hypercortisolemia led to significantly increased arterialized plasma nonesterified fatty acid (NEFA; P < 0.01) and blood glycerol concentrations (P < 0.05), with an increase in systemic glycerol appearance (P < 0.05). However, in s.c. abdominal adipose tissue, hypercortisolemia decreased veno-arterialized differences for NEFA (P < 0.05) and reduced NEFA efflux (P < 0.05). This reduction was attributable to decreased intracellular lipolysis (P < 0.05), reflecting decreased hormone-sensitive lipase action in this adipose depot. Hypercortisolemia caused a reduction in arterialized plasma TAG concentrations (P < 0.05), but without a significant change in the local extraction of TAG (presumed to reflect the action of adipose tissue lipoprotein lipase). There was no significant difference in plasma insulin concentrations between the control and hypercortisolemia study. Site-specific regulation of the enzymes of intracellular lipolysis (hormone-sensitive lipase) and intravascular lipolysis (lipoprotein lipase) may explain the ability of acute cortisol treatment to increase systemic glycerol and NEFA appearance rates while chronically promoting net central fat deposition.
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PMID:Effects of physiological hypercortisolemia on the regulation of lipolysis in subcutaneous adipose tissue. 946 84

Many unknown genetic factors are involved in the pathogenesis of hypertension. Recently, the reverse genetic approach revealed that some genetic variants, such as angiotensinogen, lipoprotein lipase, and alpha-adducin gene polymorphisms, increase the risk for hypertension. Both in rat and human, the genetic predisposition to hypertension was confirmed only for angiotensinogen and alpha-adducin genes. Adducin is a membrane cytoskeletal protein, which is thought to regulate sodium transport. Abnormalities of membrane sodium transport in the kidney play an important role in hypertension. A recent report by Cusi et al showed that the Trp allele of alpha-adducin polymorphism (Gly 460 Trp) is associated with an increased risk of hypertension in whites, which led us to carry out a case-control study to examine whether the same association is observed in the Japanese population. We recruited 170 hypertensive and 194 normotensive Japanese subjects and compared the genotype distribution of alpha-adducin 460 polymorphism between cases and controls and between whites and Japanese. Trp allele frequency of controls in the Japanese subjects was twice as high as in the whites. However, no association was observed between alpha-adducin polymorphism and hypertension. Furthermore, alpha-adducin 460 polymorphism was not associated with any clinical characteristics. Accordingly, we concluded that alpha-adducin 460 polymorphism is not a major genetic risk for hypertension in Japanese people.
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PMID:No association between alpha-adducin 460 polymorphism and essential hypertension in a Japanese population. 960 91

Endothelial function is closely related to development of atherosclerosis and is impaired with aging. The novel compound NO-1886, 4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl)benzamid e, is a lipoprotein lipase activator and its long term administration protects against the development of experimental atherosclerosis in animals. The aim of this study was to ascertain whether NO-1886 ameliorates the impaired endothelium-dependent relaxation of rat aorta associated with aging. NO-1886 (50 mg/kg p.o.) was administered to 7-month old rats for 3 months. Plasma lipid, glucose and insulin levels in old control rats (10 months of age) were significantly higher than those of young rats (2 months of age). NO- 1886 decreased plasma triglyceride levels (old rats, 233+/-10 mg/dl; old rats + NO-1886, 172+/-16 mg/dl, P < 0.01) and increased plasma high density lipoprotein (HDL) cholesterol level (old rats, 72+/-6 mg/dl; old rats + NO-1886, 142+/-6 mg/dl, P < 0.001) in old rats, but had no effects on plasma glucose or insulin. The endothelium-dependent relaxation of the thoracic aorta caused by histamine was significantly impaired in old rats (% relaxation at 10(-5.5) M histamine: young rats 25.4+/-3.1%; old rats 14.1+/-1.9%, P < 0.01), an effect completely prevented by NO-1886 (old rats + NO-1886; 22.8+/-2.8%, P < 0.05 vs. old rats). In contrast, NO-1886 showed no effect on the endothelium-independent relaxation by sodium nitroprusside. These results indicate that NO-1886 improves impaired endothelium-dependent relaxation of rat aorta associated with aging, possibly by correcting lipid metabolism.
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PMID:A lipoprotein lipase activator, NO-1886, improves endothelium-dependent relaxation of rat aorta associated with aging. 968 17

We have shown previously that apolipoprotein A (apoA)-I-containing high-density lipoprotein (HDL) particles are formed by the conjugation of lipid-free apoA-I with lipids derived from other lipoprotein fractions in a process dependent on non-esterified fatty acids, generated by the lipolysis of very-low-density lipoprotein (VLDL) or provided exogenously. In the present study, we show that this process is also able to generate HDL particles containing apoA-II (A-II HDL) and both apoA-I and apoA-II (A-I/A-II HDL). When lipid-free apoA-II was incubated with either VLDLs and lipoprotein lipase or LDLs and sodium oleate, a significant proportion of the apoA-II was recovered in the HDL density fraction. This was associated with the formation of several populations of HDL-sized particles with pre-beta2 electrophoretic mobility, which contained phospholipids and unesterified cholesterol as their main lipid constituents. When both lipid-free apoA-I and lipid-free apoA-II were incubated with LDL and sodium oleate, both apolipoproteins were recovered in HDLs that contained phospholipids and unesterified cholesterol as their main lipids. Two populations of particles had diameters of 7.4 and 10.8 nm and pre-beta2-migration; there was also a population of pre-beta1-migrating particles of diameter 4.7 nm. ApoA-I and apoA-II were both present in the larger HDLs, whereas only apoA-I was present in the smaller particles. Immunoaffinity chromatography on an anti-(apoA-I)-Sepharose column revealed that 10-20% of the apoA-II resided in particles that also contained apoA-I. The majority of the A-I/A-II HDL were present in a population of pre-beta2 particles of 10.8 nm diameter. These results in vitro illustrate a potential mechanism for the formation of HDLs containing both apoA-I and apoA-II.
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PMID:Formation of apolipoprotein-specific high-density lipoprotein particles from lipid-free apolipoproteins A-I and A-II. 989 87


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