Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trypsin, phospholipase A2, lysolecithin or non-ionic detergent polyoxyethylene p-t-octyl phenol solutions were injected into the rat biliopancreatic duct. Histological and ultrastructural changes in the gland were studied 15 min and 3 h after the injections. The rough surfaced endoplasmic reticulum disintegrated in two ways: (1) the endoplasmic reticulum in the cell periphery was vesiculated but ribosomes were well preserved at 15 min, and (2) large, round membranous structures appeared in apical cytoplasm at 3 h. Zymogen granules disintegrated in the second type, which possibly represents autodigestion. Both types of injury lead ultimately to structureless necrosis. Lesions induced by phospholipase A2 and lysolecithin were identical. Trypsin-induced damage developed slowly and the two phases of endoplasmic reticulum disintegration were not sharply separable. Lesions caused by polyoxyethylene p-t-octyl phenol were variable at 15 min, but at 3 h the type 2 injury described above was observed. It was concluded that although the initial damage in pancreatic acinar cells may vary, necrotic changes are similar despite the injected material at the later time interval. During acute pancreatitis, the acinar cell necrosis is most probably due to the action of lysolecithin produced by the activation of phospholipase A2.
Virchows Arch B Cell Pathol Incl Mol Pathol 1982
PMID:Experimental pancreatitis in the rat. Light and electron microscopical observations on early pancreatic lesions induced by intraductal injection of trypsin, phospholipase A2, lysolecithin and non-ionic detergent. 612 35

A number of compounds have been found to inhibit the internalization of alpha 2-macroglobulin and/or epidermal growth factor into fibroblasts. Using the same inhibitor we tried to block the down-regulation of prolactin receptors, supposed to mirror internalization of PRL receptors, in order to investigate the possible role of internalization in the mechanism of prolactin action. In rabbit mammary cells it appeared that bacitracin and ethylamine completely block prolactin receptor down-regulation, but dansylcadaverine, the most potent inhibitor of transglutaminase, was without effect. The blockage of phospholipase A2 by chlorpromazine or bromophenacyl bromide (BPB) was without effect on the down-regulation of prolactin receptor. Subcellular distribution of [125I]oPRL has been studied after incubation with or without these various inhibitors after fractionation of mammary gland homogenate on sucrose gradient. Any of these compounds was able to increase the labelling of prolactin receptors located in plasma membrane fractions, suggesting that the rate of internalization of prolactin was not modified. In addition, none of these compounds inhibited the stimulation of beta-casein and DNA synthesis by prolactin. These results suggest that both transglutaminase and phospholipase A2 are not involved in the mechanism of prolactin-induced down-regulation of prolactin receptors, although bacitracin and ethylamine are able to block this phenomenon probably by different mechanism. In all cases, inductions of mitogenesis and beta-casein synthesis by prolactin in the rabbit mammary cells were not modified by the various compounds utilized. We conclude that neither transglutaminase nor phospholipase A2 are involved in the internalization of prolactin-receptor complexes, although bacitracin, ethylamine and quinacrine are able to block the down regulation of prolactin receptors by other means.
Mol Cell Endocrinol 1983 Aug
PMID:Effects of transglutaminase or phospholipase A2 inhibitors on down-regulation of prolactin receptors and stimulation of casein and DNA synthesis in mammary gland explants. 613 86

We investigated whether the mitogenic response induced by local mast-cell secretion in the rat mesentery was affected by suppression of phospholipase A2, lipoxygenase, or cyclooxygenase in arachidonic acid metabolism. Enzyme inhibitor was given in a single intravenous dose 5 min before intraperitoneal injection of the mast-cell secretagogue 48/80. Mepacrine, a phospholipase A2 inhibitor, suppressed the generation of both leukotrienes (SRS) and prostaglandins (PG), whereas the lipoxygenase inhibitor BW 755C reduced the generation of SRS, and the cyclooxygenase inhibitor indomethacin significantly suppressed the generation of PG. None of the enzyme inhibitors affected the basal mesenteric histamine content or histamine release in the mesentery after exposure to 48/80, and none of them affected mast-cell-mediated mitogenesis in the mesentery as judged by specific DNA activity and mitosis counting. The stimulation of DNA synthesis and mitosis initiated by secreting mast cells is apparently not mediated or modulated by synthesis of leukotrienes, prostaglandins, or other known arachidonic acid metabolites.
Virchows Arch B Cell Pathol Incl Mol Pathol 1984
PMID:On the role of arachidonic acid metabolites in mast-cell mediated mitogenesis in the rat. 614 31

By measuring the permeability across the lipid bilayer in the presence and absence of membrane-bound protein or glycoprotein it should be possible to get an impression concerning their ability to penetrate into the membrane bilayer. Proteins such as phospholipase A2 and acetylcholinesterase markedly increase the permeability in contrast to glycoproteins (ovomucoid and orosomucoid) and cytochrome C. The results may serve as an indication of the type of interaction between lipids and membrane components.
Mol Biol Rep 1982 Apr 16
PMID:Glycoprotein and protein induced changes in liposome permeability. 628 80

The effects of endogenous phospholipase A2 activation by melittin on components of the beta adrenoceptor linked adenylate cyclase system were examined in cultured cardiac cells. Exposure of cardiac cells for one hour to melittin concentrations ranging from 0.125 microgram/ml to 5.0 micrograms/ml induced a concentration dependent hydrolysis of radioactively labelled phospholipids and loss of lysophospholipids from the cell membrane. Melittin concentrations of 2.5 micrograms/ml or greater markedly attenuated the isoprenaline induced rise in cyclic AMP. In vitro studies using cell homogenates suggest that phospholipase A2 activation by the higher concentration of melittin (5 micrograms/ml) partially uncoupled the beta adrenoceptor from adenylate cyclase. Beta adrenoceptor number estimated by 125I-iodohydroxybenzylpindolol specific binding as well as the affinity of isoprenaline for these binding sites were unaffected by melittin pre-exposure. The percentage stimulation of adenylate cyclase by sodium fluoride or guanylylimidodi-phosphate was not significantly affected by activation of endogenous phospholipase A2. Phosphodiesterase activity in the soluble fraction of cell homogenates increased marginally (9%, P = 0.05) in cells exposed to melittin. These results suggest that activation of endogenous phospholipase A2 within the sarcolemma can modulate the activity of the beta adrenoceptor linked adenylate cyclase system of intact cardiac cells. The reduced beta adrenoceptor responsiveness of the cells appears to be primarily due to an alteration in coupling between the beta adrenoceptor and the guanine nucleotide binding protein components of the adenylate cyclase system and not between the latter and the catalytic subunit.
J Mol Cell Cardiol 1983 Nov
PMID:The effects of endogenous phospholipase A2 activation on beta adrenoceptor function in cardiac cells. 631 71

A NADPH-dependent H2O2 generating system associated with a thyroid particular fraction is described. H2O2 is measured by two different methods: iodination of NADPH itself when the system is supplemented with lactoperoxidase and [125I]iodide, and by the scopoletin method. It is shown that: H2O2 generation is inhibited by catalase and is dependent on NADPH or particulate protein concentration; radical scavengers of OH and of singlet oxygen have no effect while superoxide dismutase has only a marginal effect; disruption of the particular fraction by phospholipase A2 or digitonin treatment completely abolished H2O2 generation activity while thyroid peroxidase activity appears, suggesting different sites for the two activities in the membrane vesicles.
Mol Cell Endocrinol 1984 Jun
PMID:NADPH-dependent H2O2 generation and peroxidase activity in thyroid particular fraction. 643 Jul 33

Previous studies have suggested a membrane phospholipid requirement for Rho(D) antigen activity. Isolated erythrocyte membranes incubated with phospholipase A2 from both bee venom and porcine pancreas undergo loss of Rh antigen activity. The mode of attenuation of this antigen activity as indicated by double-reciprocal binding plots suggests substantial loss of sites accompanied by an apparently increased association constant. In the presence of anti-Rho(D), but not anti-A, bound to group A Rho(D)-positive membranes prior to hydrolysis, there is marked protection: almost complete preservation of sites at the expense of a decreased association constant. This pattern of protection is not seen with phospholipase C, which cleaves the polar headgroup in contrast to the A2-enzymes, which hydrolyze the fatty acid in the 2-position. Analysis of the products of digestion shows a trend to protection of bulk phospholipids of all major classes in the presence of bound specific antibody. The hydrophobic fatty acid chain may be the site with which the bound anti-Rho(D) antibody is in closest proximity.
Mol Immunol 1984 Jun
PMID:The phospholipid requirement for Rho(D) antigen activity: mode of inactivation by phospholipases and of protection by anti-Rh0(D) antibody. 643 Dec 64

In primary cultures of bovine chromaffin cells, commercially available preparations of alpha-bungarotoxin inhibit the acetylcholine (ACh)- or nicotine-evoked release of endogenous catecholamines. The potency of different lots of alpha-bungarotoxin is not related to the alpha-bungarotoxin peptide content but to that of another peptide (termed P-4 bungarotoxin) present as an impurity in the alpha-bungarotoxin preparations. P-4 Bungarotoxin was isolated and purified to homogeneity by high-pressure liquid chromatography (HPLC). Homogeneity was established by a variety of means, including polyacrylamide gel electrophoresis, HPLC, end carboxy group analysis and NH2-terminal amino acid sequence. Purified P-4 bungarotoxin contains approximately 121 amino acid residues, and it is different in its amino composition, molecular weight, and amino acid sequence from alpha-bungarotoxin and beta-bungarotoxin. P-4 Bungarotoxin (IC50 congruent to 1 nM) blocked the ACh-induced release of endogenous catecholamines but failed to block the KCl-induced catecholamine release. Although P-4 bungarotoxin is endowed with phospholipase A2 activity, its effect on ACh-evoked catecholamine release persists when the phospholipase activity is blocked (99.9%) by treatment of the toxin with p-bromophenacyl bromide. P-4 Bungarotoxin may represent a useful tool with which to study nicotinic receptor function in sympathetic and central nervous system neurons.
Mol Pharmacol 1984 Mar
PMID:Purification and characterization of a bungarotoxin polypeptide which blocks nicotinic receptor function in primary culture of adrenal chromaffin cells. 670 May 79

Phospholipase A2 is a calcium-dependent enzyme which produces membrane fusogens. The possibility that it may be involved in exocytosis of catecholamine from primary dissociated cultures of bovine adrenal medullary cells was investigated by studying the effects on catecholamine secretion and 44Ca2+ uptake of three phospholipase A2 inhibitors: p-bromophenacyl bromide (BPB), Upjohn Compound 1002, and mepacrine. The three compounds completely inhibited catecholamine secretion induced by the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP), elevated K+, and Ba2+. The inhibition of nicotinic agonist-induced secretion by mepacrine may have been caused by direct nicotinic antagonist activity of the drug. The phospholipase inhibitors also inhibited 45Ca2+ uptake into the cells stimulated by DMPP and elevated K+. Inhibition of 45Ca2+ uptake and catecholamine secretion exhibited identical dose-response curves. Other effects of the inhibitors were also investigated. Compound 1002 had no effect on 45Ca2+ efflux from the cells in the presence of either normal or reduced Na+ concentrations. BPB inhibited DMPP-stimulated phosphorylation of tyrosine hydroxylase which, like exocytosis, is dependent on a rise in cytosolic Ca2+. The data suggest that phospholipase A2 inhibitors block catecholamine secretion from intact chromaffin cells by blocking Ca2+ influx.
Mol Pharmacol 1983 May
PMID:Phospholipase A2 inhibitors block catecholamine secretion and calcium uptake in cultured bovine adrenal medullary cells. 686 4

The previously published three-dimensional structure of porcine pancreatic prophospholipase A2 at 3 A resolution was found to be incompatible with the structures of bovine phospholipase A2 and bovine prophospholipase A2. This was unexpected because of the very homologous amino acid sequences of these enzymes. Therefore, the crystal structure of the porcine enzyme was redetermined using molecular replacement methods with bovine phospholipase as the parent model. The structure was crystallographically refined at 2.6 A resolution by fast Fourier transform and restrained least-squares procedures to an R-factor of 0.241. The crystals appeared to contain phospholipase A2 and not prophospholipase A2. Apparently the protein is slowly converted under the crystallization conditions employed. Our investigation shows that, in contrast to the previous report, the three-dimensional structure of porcine phospholipase A2 is very similar to that of bovine phospholipase A2, including the active site. Smaller differences were observed in some residues involved in the binding of aggregated substrates. However, an appreciable conformational difference is in the loop 59 to 70, where a single substitution at position 63 (bovine Val leads to porcine Phe) causes a complete rearrangement of the peptide chain. In addition to the calcium ion in the active site, a second calcium ion is present in the crystals; this is located on a crystallographic 2-fold axis and stabilizes the interaction between two neighbouring molecules.
J Mol Biol 1983 Jul 25
PMID:Structure of porcine pancreatic phospholipase A2 at 2.6 A resolution and comparison with bovine phospholipase A2. 687 74


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>