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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Native Con A and two chemical derivatives, divalent dimeric Con A and monovalent dimeric Con A. induced a transient increase of phospholipid methylation, Ca2+ influx, and also increased DNA synthesis in murine lymphocytes. For each of the individual mitogens, the dose-response curves for these three activities were very similar. However, there were major differences between the dose-response curves for Con A and each of its two chemical derivatives. On the other hand, the time course of phospholipid methylation for each lectin reached a maximum at about 10 min after the addition of lectin, and then gradually decreased to control levels. In like manner, Ca2+ influx reached its maximum at approximately 5 min. The lectin-stimulated increase in phospholipid methylation occurred in calcium-free medium, while the inhibitor of phospholipid methylation, 3-deaza-SIBA, also suppressed the increased calcium influx. This suggests that the Ca2+ influx might be regulated by early phospholipid methylation. Further, in the absence of calcium, the methylated phospholipids do not undergo Con A-accelerated breakdown by phospholipase A2. This suggests that the increased influx of calcium is necessary for the activation of phospholipase A2, an enzyme that hydrolyses methylated phospholipids to yield arachidonic acid and lysolecithin. Blocking any of these biochemical steps also blocked subsequent DNA synthesis, suggesting that the pathway may be required for the activation of lymphocytes.
Mol Immunol 1982 Feb
PMID:The relationship between phospholipid methylation and calcium influx in murine lymphocytes stimulated with native and modified Con A. 689 55

Using a primitive Earth evaporating pond model, the synthesis of phosphatidylcholine was accomplished when a reaction mixture of choline chloride and disodium phosphatidate, in the presence of cyanamide and traces of acid, was evaporated and heated at temperatures ranging from 25 degrees to 100 degrees C for 7 hours. Optimum yields of about 15% were obtained at 80 degrees C. Phosphatidylcholine was identified by chromatographic, chemical and enzymatic degradation methods. On enzymatic hydrolysis with phospholipase A2 and phospholipase C, lysophosphatidylcholine and phosphorylcholine were formed, respectively. Alkaline hydrolysis gave glycerophosphorylcholine. The synthesis of phosphatidylcholine as the major compound was accompanied by the formation of lysophosphatidylcholine in smaller amounts. Cyanamide was found to be essential for the formation of phosphatidylcholine, and only traces of HCl, of the order of that required to convert the disodium phosphatidate to free phosphatidic acid were found necessary for the synthesis. This work suggests that phosphatidylcholine, which is an essential component of most biological membranes, could have been synthesized on the primitive Earth.
J Mol Evol 1982
PMID:Synthesis of phosphatidylcholine under possible primitive earth conditions. 709 79

This review focuses on the mechanism of action of phospholipase A2 from cobra venom (Naja naja naja) toward the lipid/water interface. Particular points of interest include dramatic changes in the enzyme activity if the physical state of its substrate is altered and the activation of the enzyme by phosphorylcholine containing lipids. The experimental findings include the following: Micellar substrates are hydrolyzed faster by the enzyme than various bilayer forms of substrate aggregation. The activity of the enzyme toward short chain phospholipids increases suddenly above their critical micelle concentrations. An abrupt change in susceptibility to the enzyme is observed at the thermotropic phase transition of phospholipid vesicles. The enzyme shows the kinetic phenomena of surface dilution and activation by certain lipids, which suggest a two-step mechanism of action. A model is discussed which accommodates the present data both for the action of this enzyme at various lipid/water interfaces as well as its interaction with synthetic monomeric ligands and substrates.
Mol Cell Biochem 1981 Apr 13
PMID:Cobra venom phospholipase A2: a review of its action toward lipid/water interfaces. 724 29

The crystal structure of the dimeric (alpha 2) phospholipase A2 from Crotalus atrox has been determined by multiple isomorphous replacement to 2.5 A resolution. A skeletal model was fit to the electron density, and the stereochemistry of the backbone was idealized. The dimeric molecule is a well defined oblate ellipsoid composed of two covalently identical subunits related by a local dyad axis which is essentially "exact" except for deviations at the periphery induced by ionic lattice contacts with neighboring dimers. As expected, the basic architecture of the individual protomers is similar to the structure of the homologous monomeric bovine enzyme (Dijkstra, B. W., Drenth, J., Kalk, K., and Vandermaalen, P. J. (1978) J. Mol. Biol. 124, 53-60). The intramolecular contact surface between the protomers is extensive and involves the catalytic and calcium-binding sites. Access to an internal cavity formed by the enclosed and abutting active center regions is quite restricted. The putative interfacial recognition surfaces of each protomer are exposed to the solvent but are on opposing surfaces of the ellipsoid, suggesting that both of these regions cannot interact with the same membrane surface simultaneously unless the membrane is distorted from planarity and/or the dimer is significantly modified.
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PMID:The 2.5 A crystal structure of a dimeric phospholipase A2 from the venom of Crotalus atrox. 726 73

Phospholipase A2 interactions with phospholipid liposomes and vesicles were studied by using unhydrolysed spin-labeling 2-alkyl phosphatidylcholine. These interactions have polar nature. Phospholipase A2 hydrolyses only the neighbouring phospholipid monolayer. The hydrophobic layer of liposomes is not permeable for the enzyme. Phospholipase A2 are attached to lysophosphatidylcholine after hydrolysis and it stabilizes the structure of vesicles. The stabilizing effect of the enzyme makes the vesicles unpermeable for Na+, Cl-ions and protons. Moreover, the phospholipase A2 prevents the phospholipid exchange between the vesicles and their fusion.
Mol Biol (Mosk)
PMID:[Spin-labeling studies on interaction of phospholipase A2 from cobra poison with phospholipid membranes]. 733 72

Enzyme-substrate interaction of phospholipase A2 (Naja naja oxiana) with phospholipids has been studied. Spin-labeled palmitic and stearic acids, 1-O-spin-labeled acyl-, 2-O-spin-labeled acylphosphatidyl choline and spin-labeled phosphatidyl-myo-inositol were used for this purpose. This method did not reveal hydrofobic fat-protein interaction. Phospholipase interacts only with the near lipid monolayer of liposomes and vesicles. Being formed lysophosphatidyl choline and fat acids lead to destruction of vesicles, but phospholipase renders stabilization effect.
Mol Biol (Mosk)
PMID:[Phospholipase spin-labeled phospholipids interactions]. 740 3

The expression of different isoforms of phospholipase A2 in human and rat islets of Langerhans and in the clonal B-cell lines, HIT-T15 and RINm5F has been investigated, using polyclonal antisera specific to human cytosolic (cPLA2) or human Groups I and II secretory (sPLA2) isoforms. Abundant levels of a 100-kDa protein corresponding to cPLA2 were detected in cytosolic extracts of human islets. A 100-kDa cPLA2 was not detectable in rat islets, RINm5F or HIT-T15 cells using an anti-cPLA2 serum raised against cloned human cPLA2 cDNA, despite the antiserum being cross-reactive with cPLA2 from rat kidney. Human and rat islets were found to express a 21-kDa protein immunoreactive with Group I sPLA2 antiserum. Group II sPLA2 was not detected in human or rat islets. RIN cells did not express detectable levels of either Group I or Group II sPLA2, but HIT cells expressed variable quantities of Group II sPLA2. These differences in PLA2 expression suggest that caution should be exercised when extrapolating conclusions about lipid-derived signalling molecules from insulin-secreting cell lines to normal islets of Langerhans.
Mol Cell Endocrinol 1995 Aug 11
PMID:Phospholipase A2 expression in human and rodent insulin-secreting cells. 748 21

The cDNA sequence encoding phospholipase A2 (PLA2) was determined by analysis of polymerase-chain-reaction (PCR) product amplified from total cDNA mixture which had been constructed from the poly(A)+RNA of venom glands obtained from Taiwan cobras. Two oligonucleotide segments corresponding to the 5'- and 3'-noncoding regions of sea-snake PLA2 gene were used as primers for PCR-amplified reaction. Plasmids of transformed E. coli strain JM109 containing amplified PLA2 cDNA were purified and prepared for nucleotide sequencing by dideoxynucleotide chain-termination method. Sequencing more than five clones containing about 0.5 kb DNA inserts revealed two isoforms with complete reading frames of 468 base pairs each covering a precursor for phospholipase A2 with a deduced mature protein sequence of 119 amino acids and a 27 amino-acid signal peptide. These two enzymes of Group I PLA2 differ in six nucleotide residues at the gene level and three amino acids along the whole polypeptide chain, each consisting of 14 cysteine residues similar to all reported PLA2 of different snake venoms. The signal peptides and hydropathy profiles of Group I PLA2 reported here are distinctly different from those of Group II PLA2 in viperid snakes.
Biochem Mol Biol Int 1994 May
PMID:cDNA and protein sequences coding for the precursor of phospholipase A2 from Taiwan cobra, Naja naja atra. 752 2

Airway wall remodeling, including hyperplasia of airway smooth muscle, is regarded as an important contributor to airway hyperresponsiveness in asthmatic patients. The effects of the proinflammatory cytokine, tumor necrosis factor alpha (TNF alpha) on the mitogenic responses of human cultured airway smooth muscle have been investigated. Lower concentrations of TNF alpha (0.3 to 30 pM) had a small, delayed (48-h incubation), stimulatory effect on DNA synthesis that was blocked by dexamethasone (1 microM), aspirin (100 microM), or primaquine (30 microM) pretreatment, indicating that this effect was secondary to the release of cyclooxygenase products. TNF alpha (300 pM; 24- to 48-h incubation) alone had no effect on cell number or DNA or protein synthesis, but markedly reduced the stimulatory effects of thrombin (0.3 U/ml). TNF alpha (300 pM) also inhibited mitogenic responses to fetal calf serum (10%), epidermal growth factor (300 pM), and the thromboxane A2 mimetic U46619 (100 nM), indicating a nonselective effect. The inhibitory effects of TNF alpha (300 pM) were not blocked by pretreating the cells with the cyclooxygenase inhibitor aspirin (100 microM), the 5-lipoxygenase inhibitor CGS 8515 (3 microM), or the nitric oxide synthase inhibitor nitro-iminoethyl-L-ornithine (100 microM), suggesting that neither arachidonic acid metabolites nor nitric oxide were mediators of the inhibitory effect. The phospholipase A2 inhibitor primaquine (30 microM) had no effect on the inhibitory responses to TNF alpha, whereas the anti-inflammatory steroid dexamethasone (1 microM) prevented TNF alpha inhibition of mitogenic responses. Thus, concentrations of TNF alpha, within the range detected in bronchoalveolar lavage fluid from asthmatics, suppress mitogenic responses by a mechanism that is sensitive to inhibition by anti-inflammatory steroids, but does not appear to involve established targets for modulation by steroids, including arachidonic acid metabolism or induction of nitric oxide synthase.
Am J Respir Cell Mol Biol 1995 Jan
PMID:Tumor necrosis factor alpha modulates mitogenic responses of human cultured airway smooth muscle. 752 28

The dynamics and mechanisms of extracellular release of hydrogen peroxide (H2O2) from bovine pulmonary artery endothelial cells (EC) subjected to anoxia, hypoxia, and hypoxia followed by reoxygenation were examined using various inhibitors of enzymatic systems in intact cells and by direct measurement of H2O2 production from isolated EC plasma membranes. Extracellular H2O2 was measured with a fluorometric assay. EC exposed to hypoxia (3% O2) and anoxia (0% O2) released less H2O2 (29.6 +/- 1.3% and 4.2 +/- 0.7%, respectively) compared with EC exposed to normoxia (20% O2). The extracellular release of H2O2 from EC previously exposed to hypoxia for 24 h increased immediately after reoxygenation (20% O2) to 272 +/- 48%, as compared with EC exposed continuously to normoxia (100% release). Inhibition of xanthine oxidase (XO) by allopurinol did not reduce the release of H2O2 from cells exposed to normoxia or hypoxia followed by reoxygenation. Furthermore, inhibitors of cyclooxygenase (indomethacin), phospholipase A2 (quinacrine and chlorpromazine), nitric oxide synthase (L-arginine analogs), the mitochondrial electron transport chain (rotenone and cyanide), and cytochrome P-450 (methoxypsoralen) had no or minimal effect on this release. On the other hand, inhibitors of protein kinase C (calphostin and staurosporine) and NADPH oxidase (diphenyliodonium) reduced the release of H2O2 from EC in a dose-dependent manner in both exposure groups. In separate experiments, plasma membranes isolated from EC were found to produce H2O2 in the presence of NADH or NADPH as electron donors. This was inhibited by diphenyliodonium but not by allopurinol.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1995 Jan
PMID:Release of hydrogen peroxide in response to hypoxia-reoxygenation: role of an NAD(P)H oxidase-like enzyme in endothelial cell plasma membrane. 752 30


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