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)

The effects of progestogens on hemostatic function seems to be minimal, however, in this longterm surveillance study of the effects of Norplant among 100 healthy, nonsmoking, nonalcohol drinking, and nonlactating Singaporean women indicates the possibility of an increased predisposition of thrombosis. Clinical assessment and blood sampling were taken prior to insertion and at 6, 12, 24, 36, and 48 months. Laboratory tests included prothrombin time (PT), activated partial thromboplastic time (APTT), hematocrit and platelet count as hemostatic measures. Also measured were fibrinogen, coagulation factor II, a 1-stage assay for factors V and VII, factor VII, factor X, antithrombin III, plasminogen activator activity on the fibrin plate and FDP, platelet aggregation, factor VIIIR. 20 normal controls not on any medication were used and international standards were applied in most cases. The coefficients of variation of the various tests with reference control plasma or sera are summarized. The paired t test was used to assess statistical differences. Skewed results were analyzed with the Wilcoxon signed rank test. % changes between pre- and postinsertion levels were also utilized. The results were that the hemoglobin concentration increased from 12.1 gm/dl to 13.4 gm/dl in the 1st year, and then decreased to preinsertion levels within 3 years, and increased to 13.3 gm/dl in the 4th year. The 4th year also reflected no menstrual disorder. PT and APTT appeared significantly shortened in year 1. PT continued to shorten in 3 more years, while APTT increased to the preinsertion mean. Vitamin K dependent factors II and VII decreased significantly in year 1, while factors V and X increased significantly. Factor II increased minimally within 2 more years, but decreased again in year 4. Factor VII continued to decrease over the 4 years. The concentration of factors II and VII were significantly lower after 4 years. Factor V increased 14.4% in year 1, but decreased below preinsertion levels in the next 3 years, and then decreased to preinsertion levels in year 4. No significant changes in fibrinolytic activity occurred in 4 years. Major changes occurred in mean platelet count, which rose significantly in year 1 and increased concentration in year 4. In 4 years, platelet aggregation using ADP or equine collagen rose significantly. Serious thought must be given to the risk of thrombosis and potential for hypercoagulation.
 ...
PMID:Haemostatic function changes in Singapore women using Norplant implants: a four year review. 1228 17

Phospholipase D (PLD) is present in human placental tissue. Since purinergic receptor agonists activate PLD in many different cell types, we evaluated the purinergic activation of the enzyme in cultured trophoblasts from the placenta. We found that P(2) receptor agonists stimulate PLD. The preferred ligand for P(2X7) (P(2Z)) receptor subtype, BzBz-ATP (10(-3)M ), induced the enzyme more than ten times over basal (unstimulated) activity, while ATP caused a much smaller increase. ATPgammaS, ADP and UTP were even less effective, compared to BzBz-ATP or ATP. AMP and alpha,beta-methyl-ATP, a P(2X) agonist that is uniquely inactive on the P(2X7) subtype, had no effect. This represents the first suggestion of the presence of the P(2X7) type of receptor in human trophoblasts that was directly confirmed by immunoblot detection. The action of BzBz-ATP was dependent upon the presence of calcium in the culture medium and was inhibited by high (5m M ) Mg(++) concentration. P(2X7) receptor subtype specific antagonists, ATP-2',3'-dialdehyde (o-ATP), CBB and the broad specificity P(2) inhibitor PPADS inhibited the effect of BzBz-ATP. Pertussis toxin treatment did not inhibit the effect. Down-regulation of cPKC/nPKC isoforms by prolonged PMA treatment (36 h, 10(-7)M ) prevented the stimulation of PLD by P(2) agonists or the calcium ionophore A-23187. PLA(2) inhibitors did not block the effect of BzBz-ATP. The possibility for a calcium influx related interdependence of PLC and PLD was evaluated. For PLC activation, UTP and ATP surpassed BzBz-ATP, while ionophore did not elevate PLC (assessed by IP(3) measurements). This suggested the predominance of a P(2Y2) receptor in the whole cell in gross activation of PLC. PLD was affected with a reversed order of potency. These results and the dependence of PLD on PKC activity implies that a restricted, membrane localized calcium flux activates PKC and in turn, mediates the P(2X7) dependent stimulation of PLD. This may have implications for physiologic regulation of trophoblast function.
 ...
PMID:Regulation of phospholipase D in human placental trophoblasts by the P(2) purinergic receptor. 1236 78

P2 receptors mediate the actions of the extracellular nucleotides ATP, ADP, UTP, and UDP, regulating several physiologic responses including cardiac function, vascular tone, smooth muscle cell (SMC) proliferation, platelet aggregation, and the release of endothelial factors. P2 receptor characterization has been hampered by the lack of selective antagonists. The aim of the current study was to investigate the mRNA and protein expression of P2X and P2Y receptors in human SMC and in endothelial cells (EC). Smooth muscle cells were obtained from human mammary artery and EC from human umbilical vein. Using real-time PCR, the authors established quantitative mRNA assays. Protein expression was studied using Western blotting with recently developed antibodies. The P2X1 receptor was highly specific for human SMC, while the P2X4 was the highest expressed receptor in EC. The P2Y2 receptor was present in both SMC and EC. UTP-mediated effects in these cells are likely to be mediated by P2Y2 and not P2Y4 receptors since the latter had considerably lower expression. The P2Y6 receptor was expressed in both SMC and EC. The P2Y1 and surprisingly the P2Y11 receptors were the most abundantly expressed P2Y receptors in the endothelium. Overall, Western blotting confirmed the mRNA findings in most aspects, and most interestingly, indicated oligomerization of the P2Y1 receptor that may be important for its function. In conclusion, P2X1, P2Y2, and P2Y6 are the most expressed P2 receptors in SMC and are thus probably mediating the contractile and mitogenic actions of extracellular nucleotides. The P2X4, P2Y11, P2Y1, and P2Y2 are the most expressed P2 receptors in EC, and are most likely mediating release of nitric oxide, endothelium-dependent hyperpolarizing factor (EDHF), and t-PA induced by extracellular nucleotides. These findings will help to direct future cardiovascular drug development against the large P2 receptor family.
 ...
PMID:P2 receptor expression profiles in human vascular smooth muscle and endothelial cells. 1245 17

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

We examined the antithrombotic and thrombolytic effects of the G(q/11) inhibitor YM-254890 in an electrically-induced carotid artery thrombosis model in rats. YM-254890 dose-dependently inhibited ex vivo ADP-induced platelet aggregation after i.v. bolus injection. In the thrombosis study, YM-254890 dosedependently prolonged time to occlusion at doses of 3 and 10 g/kg i.v. and decreased occlusion rate at 10 g/kg i.v. In the thrombolysis study, YM-254890 at 30 micro g/kg i.v. shortened the time to reperfusion and prevented reocclusion after thrombolysis with a modified tissue-type plasminogen activator. YM-254890, at 10 micro g/kg and more, significantly improved carotid patency status after thrombolysis. However, at 30 micro g/kg and more, YM-254890 decreased systemic blood pressure. These results suggest that YM-254890 may be effective for treating G(q)-mediated diseases, and that YM-254890 is a useful tool for investigating the biological roles of G(q/11).
 ...
PMID:Antithrombotic and thrombolytic efficacy of YM-254890, a G q/11 inhibitor, in a rat model of arterial thrombosis. 1295 8

The aim of the present study was to compare the response of a range of atherogenic and thrombogenic risk markers to two dietary levels of saturated fatty acid (SFA) substitution with monounsaturated fatty acids (MUFA) in students living in a university hall of residence. Although the benefits of such diets have been reported for plasma lipoproteins in high-risk groups, more needs to be known about effects of more modest SFA-MUFA substitutions over the long term and in young healthy adults. In a parallel design over 16 weeks, fifty-one healthy young subjects were randomised to one of two diets: (1) a moderate-MUFA diet in which 16 g dietary SFA/100 g total fatty acids were substituted with MUFA (n 25); (2) a high-MUFA diet in which 33 g dietary SFA/100 g total fatty acids were substituted with MUFA (n 26). All subjects followed an 8-week run-in diet (reference diet), with a fatty acid composition close to the UK average values. There were no differences in plasma lipid responses between the two diets over 16 weeks of the study with similar reductions in total cholesterol (P<0.001) and LDL-cholesterol (P<0.01) in both groups; a small but significant reduction in HDL-cholesterol was also observed in both groups (P<0.01). Platelet responses to ADP (P<0.01) and arachidonic acid (P<0.05) differed with time on the two diets; at 16 weeks, platelet aggregatory response to ADP was significantly lower on the high-MUFA than the moderate-MUFA (P<0.01) diet; ADP responses were also significantly lower within this group at 8 (P<0.05) and 16 (P<0.01) weeks compared with baseline. There were no differences in fasting factor VII activity (factors VIIc and VIIag), fibrinogen concentration or tissue-type plasminogen activator activity between the diets. There were no differences in postprandial factor VIIc responses to a standard meal (area under the curve) between the diets after 16 weeks, but postprandial factor VIIc response was lower than on the high-MUFA diet compared with baseline (P<0.01). In conclusion, a high-MUFA diet sustains potentially beneficial effects on platelet aggregation and postprandial activation of factor VII. Moderate or high substitution of MUFA for SFA achieves similar reductions in fasting blood lipids in young healthy subjects.
 ...
PMID:Long-term monounsaturated fatty acid diets reduce platelet aggregation in healthy young subjects. 1312 66

We investigated the effect of highly purified eicosapentaenoic acid ethyl ester (EPA-E) on blood coagulation abnormalities and dysfunction of vascular endothelial cells in spontaneously diabetic Otsuka Long-Evans Tokushima Fatty rats. The animals were treated with either EPA-E or lard at a daily dose of 0.3 g/kg/day for 52 weeks by gavage, and their coagulation/fibrinolytic parameters, platelet aggregation, and functions of the vascular endothelial cells were examined. EPA-E significantly improved coagulation-related parameters including prothrombin time, activated partial thromboplastin time, fibrinogen level, and activities of factor II, V, VII, VIII, IX, X, XI, and XII, and antithrombin III, and fibrinolysis-related parameters including plasminogen, tissue-type plasminogen activator, alpha(2)-plasmin inhibitor, and plasminogen activator inhibitor. It also suppressed ADP- or collagen-induced platelet aggregation and the cholesterol/phospholipid molar ratio in platelet membranes at a dose of 0.3 g/kg. In addition, it significantly increased the migration activity of vascular endothelial cells, and decreased the binding of vascular endothelial cells to vascular endothelial growth factor. In contrast, lard had no effect on hypercoagulation, hypofibrinolysis, and platelet hyperaggregation but significantly aggravated the dysfunction of vascular endothelial cells. These data demonstrate that EPA-E beneficially altered certain factors known to promote thrombosis and atherosclerosis in this animal model.
 ...
PMID:Long-term administration of highly purified eicosapentaenoic acid ethyl ester improves blood coagulation abnormalities and dysfunction of vascular endothelial cells in Otsuka Long-Evans Tokushima fatty rats. 1461 17

In this study, Charlton's and Tomihisa's methods were modified to investigate the thrombolytic effect of corilagin from the Chinese herbal plant Phyllanthus urinaria L., as well as its effect on carotid artery patency status. The activity of type 1 plasminogen activator inhibitor (PAI-1) in rat plasma or platelet-released substances and tissue-type plasminogen activator (tPA) in rat plasma was assayed by use of a chromogenic substrate. The results showed that corilagin had a dose-dependent thrombolytic effect in rats. 5 mg/kg of corilagin produced a nearly similar reperfusion rate to that of 20000 U/kg of urokinase, whereas it produced a lower reocclusion rate than urokinase. Corilagin significantly inhibited PAI-1 activity in rat plasma or platelet-released substances while it elevated plasma tPA activity, in a concentration-dependent manner. Corilagin, however, had no influence on rabbit platelet aggregation. It is indicated that corilagin inhibited PAI-1 activity and increased tPA activity, and this property of corilagin is assumed to be responsible for the thrombolytic effect. Abbreviations. PO:persistent occlusion CR:cyclic reflow PP:persistent patency PAI-1:type 1 plasminogen activator inhibitor tPA:tissue-type plasminogen activator PBS:phosphate buffer solution IC (50):50 % of inhibitory concentration PRP:platelet-rich plasma ADP:adenosine diphosphate AA:arachidonic acid PAF:platelet-activating factor
 ...
PMID:Modulation of PAI-1 and tPA activity and thrombolytic effects of corilagin. 1475 26

A platelet aggregation inhibitor phospholipase A(2) (NND-IV-PLA(2)) was isolated from Naja naja (Eastern India) venom by a combination of cation and anion exchange chromatography. NND-IV-PLA(2) is the most catalytically active enzyme isolated from the Indian cobra venom. The acidic PLA(2) profile of Eastern regional Indian cobra venom is distinctly different from that of the western regional venom. However the acidic PLA(2)s from both the regions follow the pattern of increasing catalytic activity with increase in acidic nature of the PLA(2) isoform. NND-IV-PLA(2) is a Class B1 platelet aggregation inhibitor and inhibits platelet aggregation induced by ADP, collagen and epinephrine. Modification of active site histidine abolishes both catalytic activity and platelet aggregation inhibition activities while aristolochic acid, a phospholipase A(2) inhibitor has only partial effect on the two activities.
 ...
PMID:Purification of a Class B1 platelet aggregation inhibitor phospholipase A2 from Indian cobra (Naja Naja) venom. 1513 35

Activation of brain mitochondrial phospholipase(s) A(2) (PLA(2)) might contribute to cell damage and be involved in neurodegeneration. Despite the potential importance of the phenomenon, the number, identities, and properties of these enzymes are still unknown. Here, we demonstrate that isolated mitochondria from rat brain cortex, incubated in the absence of respiratory substrates, release a Ca(2+)-dependent PLA(2) having biochemical properties characteristic to secreted PLA(2) (sPLA(2)) and immunoreacting with the antibody raised against recombinant type IIA sPLA(2) (sPLA(2)-IIA). Under identical conditions, no release of fumarase in the extramitochondrial medium was observed. The release of sPLA(2) from mitochondria decreases when mitochondria are incubated in the presence of respiratory substrates such as ADP, malate, and pyruvate, which causes an increase of transmembrane potential determined by cytofluorimetric analysis using DiOC(6)(3) as a probe. The treatment of mitochondria with the uncoupler carbonyl cyanide 3-chlorophenylhydrazone slightly enhances sPLA(2) release. The increase of sPLA(2) specific activity after removal of mitochondrial outer membrane indicates that the enzyme is associated with mitoplasts. The mitochondrial localization of the enzyme has been confirmed by electron microscopy in U-251 astrocytoma cells and by confocal laser microscopy in the same cells and in PC-12 cells, where the structurally similar isoform type V-sPLA(2) has mainly nuclear localization. In addition to sPLA(2), mitochondria contain another phospholipase A(2) that is Ca(2+)-independent and sensitive to bromoenol lactone, associated with the outer mitochondrial membrane. We hypothesize that, under reduced respiratory rate, brain mitochondria release sPLA(2)-IIA that might contribute to cell damage.
 ...
PMID:Rat brain cortex mitochondria release group II secretory phospholipase A(2) under reduced membrane potential. 1523 25


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