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

Phospholipase activation with resulting phospholipid breakdown and lipid byproduct accumulation may play a critical role in hypoxic cell injury. To explore this role, mildly hypoxic rabbit renal proximal tubules (PT) in suspension were treated in vitro with exogenous phospholipase A2 (PLA2). This treatment produced severe tubule cell injury measured by alterations in tubule cation homeostasis, respiratory rates, and adenosine nucleotide metabolism. This injury was associated with loss of the major membrane phospholipids, phosphatidylcholine (PC) and phosphatidylethanolamine (PE), with accumulation of lipid byproducts, lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), and free fatty acids (FFA). Addition of fatty acid-free bovine serum albumin (BSA) to PTs reduced markedly FFA levels and improved significantly derangements in metabolic parameters of hypoxic PTs treated with exogenous PLA2, suggesting that FFA accumulation was a critical factor in this injury process. Effects of increasing durations of hypoxia (30, 45, and 60 min) with or without reoxygenation recovery demonstrated increased FFA levels, especially polyunsaturated FFA, which correlated better with the degree of hypoxic injury than alterations in membrane phospholipid and lysophospholipid levels. PTs undergoing hypoxia and reoxygenation recovery exposed to BSA were not protected. Although 60 min of hypoxia with 60 min reoxygenation produced accumulation of FFA to levels nearly identical to those seen in hypoxic PTs treated with exogenous PLA2 and BSA, with a similar distribution of various FFA species, hypoxia/reoxygenation produced a more severe degree of cell injury than that observed with hypoxia plus exogenous PLA and BSA.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The role of free fatty acids in hypoxia-induced injury to renal proximal tubule cells. 270 39

Retinal S-antigen mixed with complete Freund's adjuvant was used to induce experimental autoimmune uveitis (EAU) in guinea-pigs. Guinea-pigs receiving no treatment, was compared with test animals which received topically and systemically administered KLM-583B, a phospholipase A2 (PLA2) inhibitor, or subcutaneous (sub. cut) and topical corticosteroid treatment, as well as a test group which received cyclosporin A suc. cut. The best clinical suppression of EAU was obtained in the group treated suc. cut with KLM-538B. Steroids also suppressed the inflammation in the eyes but was not as effective as KLM-583B or cyclosporine A. PLA 2 activity in the aqueous humour and the myeloperoxidase (MPO) levels measured from iris-ciliary body were significantly lower in the groups treated suc. cut. with KLM-583B or cyclosporin A. Guinea-pigs treated suc. cut. with KLM-583B and cyclosporin A had the lowest antiserum titres to retinal S-antigen.
 ...
PMID:Suppression of experimental autoimmune uveitis in guinea-pigs by inhibition of phospholipase A2. 283 53

In isotonic saline-buffered conditions, phospholipase A2 from bee venom cleaves up to 65% of the phosphatidylcholine of the rabbit RBC membrane without causing significant hemolysis; however, the volume and the osmotic fragility of the treated RBC is modified. The osmotic behaviour of PLA-treated RBC after reincubation in autologous plasma suggests an heterogeneity in the enzymatic attack among the RBC population. In vivo RBC survival is strongly impaired by PLA treatment.
 ...
PMID:Properties of rabbit erythrocytes treated with phospholipase A2 from bee venom. 287 Aug 63

Serum from 48 patients with acute pancreatitis (21 with interstitial-edematous and 27 with necrotizing pancreatitis) was monitored for immunoreactive (IR) phospholipase A2 (PLA2) protein concentration and PLA catalytic activity. In both groups within 48 h after start of acute pancreatitis an up to tenfold increase of IR-PLA2 was demonstrable. Determination of IR-PLA2 revealed no differences between the groups. In contrast, determination of PLA catalytic activity allowed us to differentiate between patients with interstitial-edematous and necrotizing pancreatitis.
 ...
PMID:Prognostic value of serum phospholipase A in acute pancreatitis. 292 55

In this review emphasis is put on the mechanisms for the antiinflammatory and immunoregulatory role of glucocorticoids in man. Glucocorticoids have numerous effects some of which are permissive; steroids are thus important not only for what they do, but also for what they permit or enable other hormones and signal molecules to do. Some important effects are the result of altered protein synthesis due to steroidreceptor complex formation. One such protein is macrocortin which is induced by glucocorticoids. Macrocortin inhibits the enzyme phospholipase A2, thereby reducing the formation of prostaglandins and leukotriens. Steroids also reduce the release or synthesis of plasminogen activator and certain cytokines such as interleukin 1 and macrophage migration inhibitory factor. Glucocorticoids inhibit the release of histamin and lysosomal constituents of possible importance for the inflammatory response. In addition, steroids have profound effects on the circulation and distribution of white blood cells.
 ...
PMID:Antiinflammatory and immunoregulatory effects of glucocorticoids: mode of action. 307 81

Interleukin-1 (IL-1) treatment of synovial cells from rheumatoid arthritis and osteoarthritis patients resulted in a dose-dependent secretion of phospholipase A2 (PLA2). IL-1 also stimulated prostaglandin E2 and plasminogen activator synthesis, in parallel with PLA2 activation; all 3 were detectable within 6 hours of IL-1 treatment and peaked by 24 hours. Synovial cell PLA2 required calcium (5 mM) and a neutral pH (7.5) for maximal activity and appears similar to the PLA2 in synovial fluid, which has been described previously. We conclude that PLA2 can be induced by IL-1, and its secretion may contribute significantly to the inflammatory actions of IL-1.
 ...
PMID:Interleukin-1 activates phospholipase A2 in human synovial cells. 325 70

It was shown that anti-bee venom phospholipase A2 antibodies (anti-PLA) of bee keepers belong mainly to the IgG4 class. Furthermore anti-PLA of different individuals are idiotypically related to each other. This was shown by the binding of heterologous antiidiotypic antibodies, produced against anti-PLA IgG from single donors, to anti-PLA F(ab')2 of different individuals. Therefore, the anti-PLA response provides a human model to study the idiotypic regulation of isotypes in a defined system.
 ...
PMID:Isotypic and idiotypic characterization of anti-bee venom phospholipase A2 antibodies. 400 74

Although studies with interleukin-1 receptor antagonist (IL-1ra) in animal models have shown that IL-1 contributes to mortality in sepsis, the mechanisms whereby IL-1 mediates lethal effects are not well established. A possible mechanism is that IL-1 enhances the activation and release of other inflammatory mediator systems such as coagulation, fibrinolysis, neutrophils, and secretory-type phospholipase A2 (sPLA2). We investigated this possibility by assessing the effect of intravenously injected recombinant human IL-1 alpha (rhIL-1 alpha) on these plasma parameters in baboons. In addition, we examined the course of these inflammatory parameters in baboons after a challenge with a lethal dose of Escherichia coli and while receiving a 24-hour constant infusion of IL-1ra or placebo. Intravenous administration of IL-1 alpha (10 micrograms/kg) induced the formation of thrombin, as evidenced by the appearance of thrombin-antithrombin III (TAT) complexes into the circulation (peak levels, 188 +/- 92 ng/mL at 2 hours), as well as the activation of fibrinolysis, assessed by circulating plasmin-alpha 2-antiplasmin complexes (PAP complexes; peak levels, 0.4% +/- 0.03% of fully activated plasma at 1 hour), the release of tissue-type plasminogen activator (t-PA; peak levels, 6 +/- 2 ng/mL at 2 hours), and its inhibitor, plasminogen activator inhibitor (PAI; peak levels, 724 +/- 246 ng/mL at 4 hours). Il-1 alpha administration also induced the release of sPLA2 (maximal levels, 336 +/- 185 ng/mL at 8 hours), but not degranulation of neutrophils. In the septic baboons, a significant reduction of the formation of thrombin (peak TAT levels decreased from 582 +/- 78 ng/mL to 219 +/- 106 ng/mL; P < .005), the release of t-PA (peak levels decreased from 37 +/- 11 ng/mL to 17 +/- 2 ng/mL; P < .001), and its inhibitor, PAI (peak levels decreased from 2,639 +/- 974 ng/mL to 1,110 +/- 153 ng/mL; P <.001), was observed in the group receiving IL-1ra compared to that receiving placebo. The release of neutrophilic elastase was also significantly attenuated in IL-1a-treated animals (peak levels, 1,024 +/- 393 and 655 +/- 104 ng/mL in control and treatment groups, respectively; P < .05). The difference between sPLA2 levels in both groups, although higher in the controls (maximal levels, 3,140 +/- 1,435 ng/mL in control v 2,217 +/- 1,375 ng/mL in IL-1ra-treated group), was not significant. Thus, IL-1 contributes to activation of various other mediator systems in severe sepsis in nonhuman primates. We propose that these effects may explain the lethal actions of IL-1 in this sepsis model and suggest a similar role for IL-1 in severe human sepsis.
 ...
PMID:Contribution of interleukin-1 to activation of coagulation and fibrinolysis, neutrophil degranulation, and the release of secretory-type phospholipase A2 in sepsis: studies in nonhuman primates after interleukin-1 alpha administration and during lethal bacteremia. 762 Jan 56

We measured serum levels of endotoxin, cytokines, and eicosanoids and investigated their relationship to serum complement levels in patients with sepsis. Serum endotoxin (Et) levels (5.3 +/- 2.4 pg/ml) were within the normal range, but levels of tumor necrosis factor-alpha (TNF-alpha, 114 +/- 104.94 pg/ml), interleukin 6 (IL-6, 86.7 +/- 50.9 pg/ml), interleukin 8 (IL-8, 86.8 +/- 49.7 pg/ml), type-II phospholipase A2 (type II PLA2, 211.3 +/- 193.9 ng/ml), leukotriene B4 (LTB4, 88.7 +/- 27.2 pg/ml), thromboxane B2 (TXB2, 58.7 +/- 50.9 pg/ml) and 6-keto-prostaglandin F1 alpha (PGF1 alpha, 21.0 +/- 11.0 pg/ml) levels were above normal. Levels of C3a (1088.4 +/- 83.8.7 ng/ml) and C4a (1951.5 +/- 1697.8 ng/ml) were also above normal; C3 (66.0 +/- 25.6 mg/dl) and C4 (23.6 +/- 5.3 mg/dl) were within the normal range, and C5a was lower than the detectable limit in all but one of the subjects. Serum TNF-alpha was significantly correlated with C3a (p < 0.001). Serum IL-6 had a significant negative correlation with C3 (p = 0.002) and C4 (p = 0.010). Type II PLA2 was significantly correlated with C3a (p < 0.001). There were no significant correlations between serum Et or IL-8 and serum C3, C4, C3a or C4a. Our findings suggest that increased levels of TNF-alpha, IL-6, and Type II PLA/ in patients with sepsis contribute to activation of the complement system.
 ...
PMID:Blood cytokine and complement levels in patients with sepsis. 793 3

By means of gel filtration, ionic exchange chromatography and DEAE-column HPLC, an acidic phospholipase A2 (PLA2) was purified from beaded lizard (Heloderma horridum) venom. The purified PLA is a single-chain polypeptide, consisting of about 163 amino acid residues with a molecular mass of 19,000 Da as calculated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and amino acid analysis. HHV-PLA showed a rather specific inhibitory effect on platelet aggregation induced by U46619 and epinephrine in human platelet-rich plasma in a dose- and time-dependent manner, whereas it had little effect on collagen- and ADP-induced aggregation. ATP-release reaction induced by various agonists were dose- and time-dependently inhibited by HHV-PLA, even though platelet aggregation was apparently not affected in human washed platelets. When HHV-PLA was chemically modified with p-bromophenacyl bromide, both of its enzymatic activity and antiplatelet activity were lost. Furthermore, exogenous lysophosphatidylcholine and HHV-PLA treated phosphatidylcholine inhibited platelet aggregation induced by U46619 in human washed platelets. In conclusion, PLA enzyme from H. horridum venom inhibits exclusively U46619- or thromboxane-induced platelet aggregation of human platelet-rich plasma probably by virtue of their PLA enzymatic activity on plasma phospholipids, converting phospholipids (e.g., phosphatidylcholine) into lysophospholipids, which in turn interfere with the coupling of TXA2 receptor and its signalling transduction system.
 ...
PMID:Effect on human platelet aggregation of phospholipase A2 purified from Heloderma horridum (beaded lizard) venom. 812 83


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