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)

Phospholipases A(2) (PLA(2)s), of molecular mass 13-15kDa, are commonly isolated from snake venom. Two myotoxins with PLA(2) activity, BaPLA(2)I and BaPLA(2)III, with estimated molecular masses of 15kDa were isolated from the venom of Bothrops atrox using Sephacryl S-100-HR and reverse-phase chromatography. BaPLA(2)I was basic, with a pI of 9.1, while BaPLA(2)III was neutral with a pI of 6.9. On a molecular basis, BaPLA(2)III exhibited higher catalytic activity on synthetic substrates than BaPLA(2)I. Comparison of the N-terminal residues of BaPLA(2)I with other PLA(2) proteins from snake venoms showed that it has the highest homology (94%) with B. asper myotoxin II and homology with a PLA(2) Lys(49) from B. atrox (89%). In contrast, BaPLA(2)III demonstrated 75, 72, and 71% homology with PLA(2) from Vipera ammodytes meridionalis, B. jararacussu, and B. jararaca, respectively. BaPLA(2)I and BaPLA(2)III were capable, in vitro, of inducing mast cell degranulation and, in vivo, of causing creatine kinase release, edema, and myonecrosis typical of PLA(2)s from snake venoms, characterized by rapid disruption of the plasma membrane as indicated by clumping of myofilaments and necrosis of affected skeletal muscle cells. BaPLA(2)I- and BaPLA(2)III-specific monoclonal and polyclonal antibodies, although incapable of neutralizing PLA(2) edematogenic activity, blocked myonecrosis efficiently in an in vivo neutralization assay. The results presented herein suggest that the biological active site responsible for edema induction by these two PLA(2) enzymes is distinct from the myonecrosis active site and is not dependent upon the catalytic activity of the PLA(2) enzyme.
 ...
PMID:Biochemical and biological properties of phospholipases A(2) from Bothrops atrox snake venom. 1223 22

Mechanical valve thrombosis is a life-threatening event. Pregnancy is associated with a hypercoagulable state that further emphasizes the importance of adequate anticoagulation. This is associated with a therapeutic dilemma. Continued anticoagulation with warfarin throughout the first trimester can result in fetopathic effects, while replacement of warfarin by heparin between 6 and 12 weeks of gestation does not completely prevent the risk of valve thrombosis. There are a small number of reported cases of pregnant women with prosthetic heart valve thrombosis under low molecular weight heparin and consecutive lytic therapy. The authors report a 33-year-old pregnant woman with a St. Jude Medical aortic prosthesis, anticoagulated with a therapeutic dosage of low molecular weight heparin from 6 weeks of gestation, who developed prosthetic heart valve thrombosis at 17 weeks of gestation. A thrombolysis with recombinant tissue-type plasminogen activator (50 mg for 2 hours) was performed. Under thrombolysis, ST-segment elevation in leads II, III, aVF, V5, and V6 developed electrocardiographically with a maximal creatine kinase (CK) of 349 U/L (CK-MB isoenzyme of 48 U/L). Echocardiography revealed normal function of the St. Jude Medical aortic prosthesis 2 hours after thrombolysis and normal wall motions. Short-course thrombolytic therapy appears to be an effective alternative to surgical intervention for the treatment of thrombotic dysfunction of valve prostheses in pregnancy.
 ...
PMID:Successful thrombolysis of st. Jude medical aortic prosthesis with tissue-type plasminogen activator in a pregnant woman: a case report. 1239 Jun 90

In a previous report we showed that Lachesis muta crude venom displays potent indirect hemolytic activity and myotoxicity when injected into mice. Then, a phospholipase A(2) (PLA(2)) (LM-PLA(2)-I) responsible for these activities was isolated. More recently, a catalytically active isoenzyme (LM-PLA(2)-II) with molecular mass of 18 kDa and isoeletric point at pH 5.4 was isolated from the same snake venom. LM-PLA(2)-II inhibited ADP- and collagen-induced platelet aggregation as well as induced a potent paw edema reaction in rats. Here we show that LM-PLA(2)-II induced myotoxic effects both in vitro characterized by an increase on the rate of creatine kinase (CK) release from isolated mice extensor digitorum longus (EDL) muscles and in vivo by increasing plasma CK activity of injected mice. Histological analysis showed an intense damage in muscle cells injected with LM-PLA(2)-II. It was also shown that exogenous lysophosphatidylcholine (lyso-pc) behaved as a typical myotoxin damaging muscle cells, producing myonecrosis characterized by local infiltration of inflammatory cells similarly to that observed for LM-PLA(2)-II. Hemorrhage and lethal effects were not observed neither with LM-PLA(2)-II nor lyso-pc. As previously observed for other biological activities, pretreatment of LM-PLA(2)-II with p-bromophenacyl bromide (p-BPB) or acetic anhydride abolished all the enzyme's actions. The data confirms that biological activities displayed by LM-PLA(2)-II, including the myotoxic effects reported here, are all dependent on its enzymatic activity where the product formed (lyso-pc) may play an important function on such myotoxicity.
 ...
PMID:Myotoxicity induced by an acidic Asp-49 phospholipase A(2) isolated from Lachesis muta snake venom. Comparison with lysophosphatidylcholine. 1281 42

To determine whether tenecteplase (TNK-t-PA), a bioengineered variant of tissue-type plasminogen activator (t-PA) designed to accelerate thrombolysis, exhibits favorable properties compared with those of alteplase, 266 men were studied </=6 hours after the onset of symptoms and signs of acute myocardial infarction. The primary end point was the rapidity of recanalization as judged from analysis of serial changes in the concentrations in blood of isoforms of creatine kinase-MM in serially obtained blood samples. Additional end points included enzymatically estimated infarct size and mortality. Patients were treated quite promptly after the onset of symptoms. The interval from the onset of chest pain to recanalization seen with TNK-t-PA was 208 +/- 10 (SE) minutes compared with 237 +/- 9 minutes seen with alteplase (p = 0.04). Thirty-day mortality was low with the use of the 2 agents (2%). TNK-t-PA appears to induce recanalization more rapidly than alteplase, and thrombolysis initiated early after the onset of symptoms is associated with remarkably low mortality.
 ...
PMID:Comparison of rapidity of coronary recanalization in men with tenecteplase versus alteplase in acute myocardial infarction. 1519 14

The whole venom of Lachesis muta muta is preponderantly neurotoxic but moderately myotoxic on the chick biventer cervicis preparation (BCp). We have now examined these toxic activities of a basic phospholipase A(2), LmTX-I, isolated from the whole venom. LmTX-I caused a significant concentration-dependent neuromuscular blockade in the BCp. The time to produce 50% neuromuscular blockade was 14.7+/-0.75 min (30 microg/ml), 23.6+/-0.9 min (10 microg/ml), 34+/-1.7 min (2.5 microg/ml) and 39.2+/-3.6 min (1 microg/ml), (n=5/concentration; p<0.05). Complete blockade with all tested concentrations was not accompanied by inhibition of the response to ACh. At the highest concentration, LmTX-I (30 microg/ml) significantly reduced contractures elicited by exogenous KCl (20mM), increased the release of creatine kinase (1542.5+/-183.9 IU/L vs 442.7+/-39.8 IU/L for controls after 120 min, p<0.05), and induced the appearance of degenerating muscle fibers ( approximately 15%). Quantification of myonecrosis indicated 14.8+/-0.8 and 2.0+/-0.4%, with 30 and 10 microg/mlvenom concentration, respectively, against 1.07+/-0.4% for control preparations. The findings indicate that the basic PLA(2) present on venom from L. m. muta (LmTX-I) possesses a dominant neurotoxic action on isolated chick nerve-muscle preparations, whereas myotoxicity was mainly observed at the highest concentration used (30 microg/ml). These effects of LmTX-I closely reproduce the effects of the whole venom of L. m. muta in chick neuromuscular preparations.
 ...
PMID:Functional characterization of a basic D49 phospholipase A2 (LmTX-I) from the venom of the snake Lachesis muta muta (bushmaster). 1662 76

Prolonged physical exercise is associated with multiple changes in blood hemostasis. Eccentric muscle activation induces microtrauma of skeletal muscles, inducing an inflammatory response. Since there is a link between inflammation and coagulation we speculated that downhill running strongly activates the coagulation system. Thirteen volunteers participated in the Tyrolean Speed Marathon (42,195 m downhill race, 795 m vertical distance). Venous blood was collected 3 days (T1) and 3 h (T2) before the run, within 30 min after finishing (T3) and 1 day thereafter (T4). We measured the following key parameters: creatine kinase, myoglobin, thrombin-antithrombin complex, prothrombin fragment F1 + 2, D-dimer, plasmin-alpha(2)-antiplasmin complexes, tissue-type plasminogen activator antigen, plasminogen-activator-inhibitor-1 antigen and thrombelastography with ROTEM [intrinsic pathway (InTEM) clotting time, clot formation time, maximum clot firmness, alpha angle]. Thrombin generation was evaluated by the Thrombin Dynamic Test and the Technothrombin TGA test. Creatine kinase and myoglobin were elevated at T3 and further increased at T4. Thrombin-antithrombin complex, prothrombin fragment F1 + 2, D-dimer, plasmin-alpha(2)-antiplasmin complexes, tissue-type plasminogen activator antigen and plasminogen-activator-inhibitor-1 antigen were significantly increased at T3. ROTEM analysis exhibited a shortening of InTEM clotting time and clot formation time after the marathon, and an increase in InTEM maximum clot firmness and alpha angle. Changes in TGA were indicative for thrombin generation after the marathon. We demonstrated that a downhill marathon induces an activation of coagulation, as measured by specific parameters for coagulation, ROTEM and thrombin generation assays. These changes were paralleled by an activation of fibrinolysis indicating a preserved hemostatic balance.
 ...
PMID:Blood coagulation activation and fibrinolysis during a downhill marathon run. 1758 17

Scatophagus argus of the family Scatophagidae inflicts painful wounds in fishermen during handling. The clinical picture is characterized by excruciating and persistent local pain disproportionate to the size of injury, redness, swelling and a throbbing sensation that extends to the limbs, followed by dizziness. The biological properties of the S. argus venom were studied to assess its risk and lethal factors with regard to human welfare. In contrast to other fish venoms, S. argus showed relatively low LD50 (9.8 mg/kg via i.p.). Haemolytic activity in human erythrocytes was recorded. Platelet lysis expressed as LDH activity of lysed cells was dose dependent. S. argus venom failed to induce any clot in human plasma. No PLA(2) activity was found in S. argus venom. Mild proteolytic activity was observed. The injection of venom in mice produced lesions and nociception, which were not inhibited by antihistamine pheniramine maleate, suggesting that histamine was not involved in the inflammatory process. The increase in serum creatine kinase activity indicated myotoxicity. Cytotoxicity on HeLa cells was observed. The spectrum of activity in experimental animals of S. argus crude venom resembles those of other fish venoms previously studied and well correlated to the systemic manifestations that are described for S. argus envenomation.
 ...
PMID:Biological and biochemical properties of Scatophagus argus venom. 1759 79

The patterns of myotoxicity induced in mice by crotoxin, crotoxin B and a Lys49 phospholipase A(2) (PLA(2)) homologue were compared. Lys49 PLA(2)-induced local myotoxicity is reflected by creatine kinase (CK) loss in injected gastrocnemius muscle, and by a profile of CK increase in plasma characterized by a rapid increment and drop after intramuscular injection, and by a lack of CK increase in plasma after intravenous injection. In contrast, crotoxin and crotoxin B, which induce local and systemic myotoxicity, provoked a more prolonged increment in plasma CK activity upon intramuscular injection, and induced increments in plasma CK after intravenous injection. The three toxins promoted a similar extent of local myotoxicity, assessed by the loss of CK in injected gastrocnemius. A method for the quantitative assessment of the ability of toxins to induce systemic myotoxicity is proposed, based on the estimation of the ratio between the area under the curve in the plasma CK activity (total myotoxicity) to the loss of CK in injected gastrocnemius (local myotoxicity). The highest ratio corresponded to crotoxin, and the lowest corresponded to Lys49 PLA(2), the former being a systemic myotoxin and the latter a local myotoxin. Neutralization by antivenoms also differed between the toxins: a drastic reduction in plasma CK, with very poor neutralization of local CK loss, was achieved in the case of crotoxin B when antivenom was injected intravenously, whereas no neutralization was achieved in the case of Lys49 PLA(2). When tested in undifferentiated myoblasts in culture, Lys49 PLA(2) induced cytotoxicity, whereas crotoxin and crotoxin B did not, evidencing that the latter are devoid of widespread cytolytic activity. Molecular modeling analysis showed that Lys49 PLA(2) has a conspicuous cationic face, which is likely to interact with diverse membranes. In contrast, crotoxin B, despite its overall basic pI, has a lower density of positively charged residues at this molecular region. It is suggested that Lys49 PLA(2)s homologues interact, through this cationic face, with many different cell types, thus lacking specificity for muscle cells. In contrast, crotoxin B has a more selective interaction with targets in the muscle cell membrane. This selectivity might be the basis for the ability of crotoxin and crotoxin B to induce systemic myotoxicity.
 ...
PMID:Systemic and local myotoxicity induced by snake venom group II phospholipases A2: comparison between crotoxin, crotoxin B and a Lys49 PLA2 homologue. 1791 77

We have investigated the cardiotoxic effect of Bothrops jararacussu crude venom and the ability of suramin to antagonize this effect in the heart of rats, as well as the proteolytic and phospholipase A(2) (PLA(2)) venom activities. Continuous perfusion in an isolated heart of a rat on a Langendorff preparation with a Ringer's solution with B. jararacussu crude venom (2.5-10.0 microg/mL) induces stoppage and a decrease in the cardiac tension, which were time- and concentration dependent. The analysis of the heart perfusate solution showed an increase in the rate of creatine kinase induced by the venom. Pre-incubation with suramin (1.0-30.0 microM) protected against the venom cardiotoxic effect in a concentration-dependent way, reaching up to 90% with 30.0 microM, and prevent the heart stoppage and decrease the tension. These protective effects were increased by the association with polyvalent antibothropic antivenom, suggesting a synergic effect. The PLA(2) and proteolytic activities of B. jararacussu crude venom were also inhibited in a concentration-dependent way by suramin, showing that this polyanion antivenom activity has therapeutic potential to be used as an antivenom.
 ...
PMID:Ability of suramin to antagonize the cardiotoxic and some enzymatic activities of Bothrops jararacussu venom. 1802 64

This study is to investigate the long-term effects of nanodimension PEG-PLA artificial red blood cells containing hemoglobin and red blood cell enzymes on the liver and spleen after 1/3 blood volume top loading in rats. The experimental rats received one of the following infusions: Nano artificial red blood cells in Ringer lactate, Ringer lactate, stroma-free hemoglobin, polyhemoglobin, and autologous rat whole blood. Blood samples were taken before infusions and on days 1, 7, and 21 after infusions for analysis. Nano artificial red blood cells, polyhemoglobin, Ringer lactate and rat red blood cells did not have any significant adverse effects on alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatine kinase, amylase and creatine kinase. On the other hand, stroma-free hemoglobin induced significant adverse effects on liver as shown by elevation in alanine aminotransferase and aspartate aminotransferase throughout the 21 days. On day 21 after infusions rats were sacrificed and livers and spleens were excised for histological examination. Nano artificial red blood cells, polyhemoglobin, Ringer lactate and rat red blood cells did not cause any abnormalities in the microscopic histology of the livers and spleens. In the stroma-free hemoglobin group the livers showed accumulation of hemoglobin in central veins and sinusoids, and hepatic steatosis. In conclusion, injected nano artificial red blood cells can be efficiently metabolized and removed by the reticuloendothelial system, and do not have any biochemical or histological adverse effects on the livers or the spleens.
 ...
PMID:Long-term effects on the histology and function of livers and spleens in rats after 33% toploading of PEG-PLA-nano artificial red blood cells. 1904 18


<< Previous 1 2 3 4 5 6 Next >>