Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We compared the diagnostic and prognostic utility of phospholipase A (PLA; EC 3.1.1.4) for acute pancreatitis with that of amylase and lipase by analysis of sera from 151 consecutive patients presenting with abdominal pain in whom assays of serum amylase and (or) lipase had been ordered. We determined the diagnostic accuracy for both the initial and the peak enzyme activities. Maximal diagnostic accuracy obtained for the initial activities of amylase, lipase, and PLA was 0.83, 0.83, and 0.76 at cutoff values of 650, 650, and 41 U/L, respectively. Use of peak enzyme activities showed maximal diagnostic accuracy of 0.85, 0.86, and 0.73 at cutoff values of 650, 1050, and 42 U/L, respectively. Receiver-operator characteristic curve analysis revealed the diagnostic performance of amylase and lipase to be similar, whereas that of PLA was almost random and not incremental. As with amylase and lipase, PLA activities in sera showed no relation to patients' survival; three patients who died after an attack of acute pancreatitis failed to demonstrate the dramatic increases in PLA activity previously described. We conclude that assessing the severity of acute pancreatitis by using enzyme activities still remains problematical. Measurements of amylase or lipase activities provide similar diagnostic discrimination when appropriate cutoff values are used and remain the methods of choice for diagnosis of acute pancreatitis.
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PMID:Diagnostic and prognostic utility of phospholipase A activity in patients with acute pancreatitis: comparison with amylase and lipase. 191 91

Several problems have frustrated the isolation of lamellar bodies (LB) from mammalian epidermis. We obtained pellets enriched in intact LB by utilizing the staphylococcal epidermolytic toxin to provide intact, outer epidermal sheets, by controlled homogenization in a cell disrupter, and by passage of homogenates through a graded series of nuclepore filters (Science 221:962, 1983). Such preparations contained more intact LB than did fractions prepared by a variety of differential or sucrose/metrizamide discontinuous centrifugation methods. Initial characterization of the enzymatic content of this fraction revealed it to be enriched in certain hydrolytic enzymes (acid phosphatase, carboxypeptidase, cathepsin B, acid lipase, sphingomyelinase, and phospholipase A), but strikingly depleted in all sulfatases, beta-glucuronidase, and the non-lysosomal protease, plasminogen activator. Thus, LB show some properties of lysosomes, although certain characteristic lysosomal enzymes are strikingly absent. Lamellar body fractions contained 2-3 times more lipid per unit weight than did homogenates, and were enriched in phospholipids, free sterols, and glycosphingolipids, but not in other neutral lipids or ceramides. In summary, whereas some of the enzymes in LB could participate in the metabolism of LB lipid precursors to hydrophobic barrier constituents, others may attack intercellular constituents, ultimately resulting in desquamation. The lipid profile of these organelles suggests that they deliver precursors of permeability barrier lipids to intercellular domains.
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PMID:Lamellar body-enriched fractions from neonatal mice: preparative techniques and partial characterization. 404 17

The genes coding for glucose regulated protein, 78kDal (GRP78), hormone-sensitive lipase (LIPE), plasminogen activator or urokinase (PLAU), and D-amino acid oxidase (DAO) were localized in the pig by radioactive in situ hybridization. GRP78 was mapped to 1q2.10-->q2.13 and LIPE was localized to chromosome 6cen-->q1.2. The genes for PLAU and DAO were both assigned to chromosome 14, in the region q2.4-->q2.6 and q2.1-->q2.3, respectively. The results are compared to mapping data in other mammalian species.
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PMID:Localization of four new markers to pig chromosomes 1, 6, and 14 by radioactive in situ hybridization. 810 65

Male WBN/Kob rats derived from the Wistar strain spontaneously develop chronic pancreatitis as late as 3 months old. To assess the degree of disease severity, we compared the lipolytic enzyme levels in pancreas of 2-, 4-, and 6-month-old WBN/Kob rats fed isocaloric no fat (NF) and high fat (HF, 57% of total calories) diets and its pathology. Diet treatment did not significantly affect lipase and group Ib phospholipase A(2) (PLA(2)) levels in the pancreas at all ages. Development of chronic pancreatitis at the age of 4 and 6 months was consistent with the tendency of decreasing group Ib PLA(2) specific content determined by enzyme immunoassay and lipase activity, and the decreased number of group Ib PLA(2)-positive acinar cells. Pancreatic lipase and group Ib PLA(2) levels of 4-month-old WBN/Kob rats were significantly lower than those of control Wistar rats at age 4 months irrespective of diet. This allowed us to adopt 4-month-old WBN/Kob rats as a model of pancreatic insufficiency, which could be a useful tool to examine the role of gastrointestinal enzymes in lipid digestion. Ca(2+)-independent PLA(2) activity of brush border membrane-associated phospholipase B/lipase (PLB/LIP) in ileal mucosa increased significantly in 4-month-old WBN/Kob rats while its content and transcript levels remained constant, suggesting its activation at the enzyme level. In WBN/Kob rats fed the HF diet at age 4 months, PLA(2) activity catalyzed by PLB/LIP in the proximal ileal mucosa was four times the total PLA(2) activity in the intestinal lumen. These results indicate that PLB/LIP compensates for the depletion of pancreatic lipolytic enzymes in WBN/Kob rats with pancreas insufficiency.
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PMID:Increased intestinal phospholipase A(2) activity catalyzed by phospholipase B/lipase in WBN/Kob rats with pancreatic insufficiency. 1101 77

The classical Ca(2+)-independent phospholipase A(2) enzyme, now known as Group VIA PLA(2), was initially purified and characterized from the P388D(1) macrophage-like cell line. The corresponding cDNA was subsequently cloned from a variety of sources, and it is now known that multiple splice variants of the enzyme are expressed, some of which may act as negative regulators of the active enzyme. Group VIA PLA(2) has a consensus lipase motif (GTSTG) containing the catalytic serine, is 85-88 kDa, and exists in an aggregated form. The enzyme contains multiple ankyrin repeats, which may play a role in oligomerization. The Group VIA enzyme exhibits lysophospholipase activity as well as phospholipase A(2) activity, and it is capable of hydrolyzing a wide variety of phospholipid substrates. A major function of Group VIA PLA(2) is to mediate phospholipid remodeling, but the enzyme may play other roles as well. Other Ca(2+)-independent PLA(2) enzymes have more recently been identified, and it may be possible to discriminate between the various Ca(2+)-independent PLA(2) enzymes based on sequence or inhibitor-sensitivity. However, the physiological functions of the newly identified enzymes have yet to be elucidated.
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PMID:Calcium-independent phospholipase A(2): structure and function. 1108 Jun 74

We previously showed that arachidonic acid and related unsaturated free fatty acids (U-FFAs) inhibit the activity of adenylylcyclase in brain membranes of mice. The level of U-FFAs elevates when the hydrolysis of triacylglycerols (TAGs) and phospholipids is promoted. In this study, we examined whether activation of triacylglycerol lipase (TAG lipase) and phospholipase A(2) (PLA(2)) results in the inhibition of adenylylcyclase activity in cerebellum membranes of mice. Incubation of Intralipos with TAG lipase in the presence of membranes mainly released oleic acid and linoleic acid and caused > or =95% inhibition of adenylylcyclase activity. In contrast, PLA(2), though releasing substantial amounts of U-FFAs, increased the enzymatic activity. To account for this difference, we examined how by-products formed in U-FFA release by TAG lipase and PLA(2) operated on the arachidonic acid-induced inhibition. Lysophosphatidylcholne and some other lysophospholipids, produced by PLA(2), enhanced the adenylylcyclase activity and attenuated the inhibitory effect of arachidonic acid. On the other hand, no such effects were found with by-products of TAG lipase-mediated lipolysis. Rather, monoacylglycerols having U-FFAs, possibly formed by TAG lipase, potentiated the arachidonic acid-induced inhibition of adenylylcyclase. Bovine serum albumin, added into the mixture for the pretreatment of membranes with TAG lipase, prevented the inhibition of adenylylcyclase. These results indicate that by-products formed in U-FFA release have a crucial role for the U-FFA's action on adenylylcyclase and that U-FFAs released from TAG are an inhibitor of adenylylcyclase. It may be that albumin in plasma, and thus FFA-binding proteins within cells, are of importance in protecting adenylylcyclase upon U-FFA release.
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PMID:Inhibition of adenylylcyclase activity in mouse cerebellum membranes upon hydrolysis of triacylglycerols by triacylglycerol lipase, but not phospholipids by phospholipase A(2). 1151 69

In several neuronal systems, nerve growth factor (NGF) and platelet-derived growth factor (PDGF) act as neurogenic agents, whereas epidermal growth factor (EGF) acts as a mitogenic agent. Hippocampal stem cell lines (HiB5) immortalized by the expression of a temperature-sensitive SV40 large T antigen also respond differentially to EGF and PDGF. While EGF treatment at the permissive temperature induces proliferation, the addition of PDGF induces differentiation at the non-permissive temperature. However, the mechanism responsible for these different cellular fates has not been clearly elucidated. In order to clarify possible critical signaling events leading to these distinct cellular outcomes, we examined whether either EGF or PDGF differentially induces the activation of phospholipases, such as phospholipase A(2) (PLA(2)), C (PLC), or D (PLD). Although EGF stimulation did not induce phospholipases, PDGF caused a rapid and transient activation of PLC and PLD, but not PLA(2). When the activation of PLC or PLD was blocked, the neurite outgrowth induced by PDGF was significantly inhibited. Although the activation of PLD occurred faster than PLC, blocking of PLD activity by transient expression of lipase-inactive mutants did not inhibit the induction of PLC activity by PDGF. These results suggest that the differential activation of phospholipases may play an important role in signal transduction by mitogenic EGF and neurotrophic PDGF in HiB5 neuronal hippocampal stem cells. In particular, the activation of phospholipase C and D may contribute to neuronal differentiation by neurogenic PDGF in the HiB5 cells.
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PMID:Differential activation of phospholipases by mitogenic EGF and neurogenic PDGF in immortalized hippocampal stem cell lines. 1155 78

The effects of recombinant mouse stem cell factor (rmSCF) on paired-pulse facilitation (PPF) and long-term potentiation (LTP) in the mossy fiber (MF)-CA3 pathway were examined in mouse hippocampal slices by recording field EPSPs. When PPF was measured before and 30 min after tetanic stimulation, the initial PPF positively correlated with the amplitude of LTP and negatively correlated with changes in PPF (PPF after LTP minus initial PPF), indicating a presynaptic component in MF-CA3 LTP. Bath application of rmSCF for 30 min also produced negative correlation between initial PPF and changes in PPF after rmSCF, suggesting common mechanisms of the LTP- and rmSCF-induced modulation of PPF. The rmSCF-induced negative correlation was abolished by simultaneous perfusion with K252a, a receptor tyrosine kinase inhibitor, and by wortmannin, a phosphatidylinositol-3'-kinase inhibitor. Although SCF activates phospholipase A(2) (PLA(2)) and diacylglycerol (DAG) lipase to produce arachidonic acid (AA) in mast cells, mepacrine, a PLA(2) inhibitor, but not RHC80267, a DAG lipase inhibitor, abolished the negative correlation. The induction of LTP was prevented by perfusion with rmSCF started 30 min before tetanus, while preincubation of slices with antibody for SCF receptor, c-kit, blocked LTP, suggesting that the intrinsic SCF is involved in the induction of LTP and the blockade of LTP by rmSCF might be due to an occlusion of SCF/c-kit signaling. In addition, since c-kit is expressed on the postsynaptic CA3 neurons but not on the MF terminals in mice, effects of rmSCF on PPF may be mediated by the PLA(2)-induced AA acting as a retrograde messenger.
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PMID:Stem cell factor modulates paired-pulse facilitation and long-term potentiation in the hippocampal mossy fiber-CA3 pathway in mice. 1213 20

Phospholipase A(2) (PLA(2)) was purified to homogeneity from the supernatant fraction of rat testis homogenate. The purified 63-kDa enzyme did not require Ca(2+) ions for activity and exhibited both phosphatidic acid-preferring PLA(2) and monoacylglycerol lipase activities with a modest specificity toward unsaturated acyl chains. Anionic detergents enhanced these activities. Serine-modifying irreversible inhibitors, (p-amidinophenyl) methanesulfonyl fluoride and methylarachidonyl fluorophosphonate, inhibited both activities to a similar extent, indicating a single active site is involved in PLA(2) and lipase activities. The sequence of NH(2)-terminal 12 amino acids of purified enzyme was identical to that of a carboxylesterase from rat liver. The optimal pH for PLA(2) activity (around 5.5) differed from that for lipase activity (around 8.0). At pH 5.5 the enzyme also hydrolyzed bis(monoacylglycerol) phosphate, or lysobisphosphatidic acid (LBPA), that has been hitherto known as a secretory PLA(2)-resistant phospholipid and a late endosome marker. LBPA-enriched fractions were prepared from liver lysosome fractions of chloroquine-treated rats, treated with excess of pancreatic PLA(2), and then used for assaying LBPA-hydrolyzing activity. LBPA and the reaction products were identified by microbore normal phase high performance liquid chromatography/electrospray ionization ion-trap mass spectrometry. These enzymatic properties suggest that the enzyme can metabolize phosphatidic and lysobisphosphatidic acids in cellular acidic compartments.
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PMID:Purification and properties of a phospholipase A2/lipase preferring phosphatidic acid, bis(monoacylglycerol) phosphate, and monoacylglycerol from rat testis. 1222 68

Guinea pig gallbladder muscle strips were used to investigate the contribution of different sources of diacylglicerol (DAG) in the cholecystokinin (CCK)-induced contraction. The involvement of arachidonic acid (AA) in this response was also investigated. Three distinct pathways for DAG production were investigated with specific phospholipase (PL) inhibitors. U-73122 (10 microM) was used for inhibition of phosphoinositide-specific-PLC (PI-PLC), D-609 (100 microM) for phosphatidylcholine specific-PLC (PC-PLC), and propranolol (100 microM) for phospholipase D (PLD). Separate or combined inhibition of each of these enzymes showed that the CCK-induced output of DAG involves the parallel activation of each of these phospholipases. Thus, after inhibition of a PL subtype, the remaining subtypes were able to functionally compensate in mediating CCK-induced contraction. Inhibition of AA production via DAG-lipase or phospholipase A(2) (PLA(2)) was accomplished using RHC-80267 (40 microM), mepacrine (100 microM) and 4-BPB (100 microM). These inhibitors diminished contractile response, indicating that AA is an important modulator of CCK-induced contraction. Indomethacin (10 microM) and nordihydroguaiaretic acid (NDGA, 100 microM), which inhibit subsequent steps in AA metabolism through the cyclooxygenase and 5-lipooxygenase pathways, also inhibited contractions. Taken together, these results show that CCK redundantly activates PC-PLC, PI-PLC and PLD, to produce DAG, which in turn stimulates PKC and provides a substrate for the generation of AA. sPLA(2) is also a source of AA, whose metabolites are, in part, responsible for determining the magnitude of the CCK-evoked contraction.
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PMID:Contribution of different phospholipases and arachidonic acid metabolites in the response of gallbladder smooth muscle to cholecystokinin. 1223 20


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