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

Eleven healthy subjects volunteered to participate in a fiber supplement study and were instructed to consume oat husk tablets in addition to their regular diets. During a 2-week experimental period the subjects consumed 10 g oat husk per day. Blood samples were collected before breakfast between 8:00 and 9:00. As compared to baseline, 10 g oat husk supplementation per day resulted in a reduction of plasma plasminogen activator inhibitor type 1 (PAI-1) activity (p < 0.05). Except for an increase in glucose, no other statistically significant deviation from baseline was observed in measured blood parameters; tissue plasminogen activator activity, prourinary plasminogen activator, coagulation factor VII, total cholesterol, HDL cholesterol, LDL cholesterol, lipoprotein (a), triglycerides and insulin. A 6-week washout period returned the PAI-1 activity level to baseline.
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PMID:Oat husk fiber decreases plasminogen activator inhibitor type 1 activity. 838 89

Elevated plasma levels of fibrinogen, factor VII coagulant activity (F VIIc), and plasminogen activator inhibitor (PAI-1) have been reported to be strictly associated with thrombotic events and are considered to be important risk markers of atherothrombotic cardiovascular disease. Therefore, we evaluated in 15 patients on continuous ambulatory peritoneal dialysis (CAPD) the plasma levels of these coagulation factors, basal insulin values, and the lipid pattern in comparison with 33 hemodialysis (HD) patients and 59 healthy subjects. In CAPD the total cholesterol and triglyceride results were significantly increased, but no difference was found in HDL cholesterol. Fibrinogen and F VIIc results were significantly higher in CAPD and HD than in the control group, probably due to an increased hepatic synthesis as a nonspecific response to the peritoneal protein loss. Elevated F VIIc activity may be caused by the presence of large negatively charged lipoproteins, in vivo thrombin formation, or reduced hepatic clearance. Both PAI 1 and t-PA results were higher in CAPD, probably due to an increased synthesis by endothelial cells activated by glucose peritoneal absorption and hypertonic dialysis solutions. The contemporary elevation of fibrinogen, F VIIc, PAI-1, and t-PA suggests that CAPD patients present a hypercoagulability and hypofibrinolysis condition, which may promote the development of atherothrombotic events.
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PMID:Risk factors of ischemic cardiac disease in patients on continuous ambulatory peritoneal dialysis. 839 23

Since plant-pathogenic fungi must penetrate through pectinaceous layers of the host cell wall, pectin-degrading enzymes are thought to be important for pathogenesis. Antibodies prepared against a pectin-inducible pectate lyase (pectate lyase A [PLA]) produced by a phytopathogenic fungus, Fusarium solani f. sp. pisi (Nectria haematococca, mating type VI), was previously found to protect the host from infection. The gene (pelA) and its cDNA were cloned and sequenced. Here we report the isolation of a new pectate lyase gene, pelB, from a genomic library of F. solani f. sp. pisi with the pelA cDNA as the probe. A 2.6-kb DNA fragment containing pelB and its flanking regions was sequenced. The coding region of pelB was amplified by reverse transcription-mediated PCR, using total RNA isolated from F. solani pisi culture grown in the presence of glucose as the sole carbon source. The predicted open reading frame of pelB would encode a 25.6-kDa protein of 244 amino acids which has 65% amino acid sequence identity with PLA from F. solani f. sp. pisi but no significant homology with other pectinolytic enzymes. The first 16 amino acid residues at the N terminus appeared to be a signal peptide. The pelB cDNA was expressed in Pichia pastoris, yielding a pectate lyase B (PLB) which was found to be a glycoprotein of 29 kDa. PLB was purified to homogeneity by using a two-step procedure involving ammonium sulfate precipitation followed by Superdex G75 gel filtration chromatography. Purified PLB showed optimal lyase activity at pH 10.0. A rapid drop in the viscosity of the substrate and Mono Q anion-exchange chromatography of the products generated by the lyase showed that PLB cleaved polygalacturonate chains in an endo fashion. Western blotting (immunoblotting) with antibodies raised against PLA showed that PLB and PLA are immunologically related to each other. The 5' flanking regions of both pelA and pelB were translationally fused to the beta-glucuronidase gene and introduced into F. solani f. sp. pisi, and beta-glucuronidase activities of the transformants were measured. Expression of the marker gene by the transformants showed that pelA expression is induced by pectin and repressed by glucose, whereas expression of pelB is constitutive and is not subject to glucose repression. Reverse transcription-mediated PCR showed that both pelA and pelB are expressed when F. solani f. sp. pisi infects pea epicotyl.
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PMID:Cloning of a novel constitutively expressed pectate lyase gene pelB from Fusarium solani f. sp. pisi (Nectria haematococca, mating type VI) and characterization of the gene product expressed in Pichia pastoris. 852 11

The authors tested in vitro the effect of glucose-based and amino acid-based dialysate effluent on the function of human peritoneal mesothelial cells. After 9 days of exposure to the tested effluents with medium (1:1 v/v) or to a medium supplemented with 10% fetal calf serum (FCS) (control), several functional properties of the cells were studied. The synthesis of DNA measured by incorporation of 3H-methyl-thymidine was higher in mesothelial-cell monolayers exposed to the dialysates than in the controls. Synthesis of hyaluronic acid was similar in all three groups, but after stimulation with Il-1 the cells exposed to the dialysates produced more hyaluronic acid. Synthesis of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) was higher in the control cells. However, after stimulation with IL-1, the cells exposed to the dialysate showed greater synthesis of PAI-1 than of t-PA. Also, procoagulant activity of the control cells was higher than that of the cells exposed to the dialysates. We have concluded that the functional properties of the mesothelial cells may be altered in vitro during prolonged exposure to the dialysate, something that may also occur in vivo.
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PMID:Functional properties of mesothelial cells after prolonged exposure to dialysate effluent. 853 91

An increased risk of ischemic heart disease in men with the Lewis blood group phenotype Le(a-b-) has been reported. It has been suggested that the Le(a-b-) phenotype is a genetic marker of the insulin resistance syndrome. To examine whether Le(a-b-) confers the insulin resistance syndrome, we studied a random sample of unrelated healthy young white men and women living in Copenhagen (n = 380, 18 to 32 years). All individuals had their insulin sensitivity estimated using Bergman's minimal model (intravenous glucose in combination with tolbutamide) and systolic blood pressure (SBP) was measured with a London School of Hygiene Sphygmomanometer. A number of anthropometric measurements including body mass index (BMI, kilograms/meters squared) and biochemical characteristics were performed. The Lewis blood group typing was carried out on erythrocytes. Twenty-one men had the Le(a-b-) phenotype. Compared to all other men (N = 165), the Le(a-b-) men had a significantly higher SBP (6 mm Hg, P = .0024). They also had higher values of BMI (8%, P = .016), total body fat mass (25%, P = .015), fasting values of serum insulin (32%, P = .006), serum C-peptide (20%, P = .029), and plasma glucose (8%, P = .003). The fasting values of serum lipids, plasminogen activator inhibitor (PAI-1) activity, tissue plasminogen activator (t-PA) antigen, and insulin sensitivity did not differ between Le(a-b-) men and men with other Lewis phenotypes. Altogether 194 women participated in the study of which 21 women had the Le(a-b-) phenotype. Except for a lower PAI-1 activity (45%, P = .044), no values differed between Le(a-b-) women and women with other Lewis phenotypes. The women were also stratified according to use of oral contraceptives. Le(a-b-) women using oral contraceptives (N = 8) had a significantly lower plasma level of fasting PAI-1 activity (P = .029) and t-PA antigen (P = .004) compared to women using oral contraceptives without the Le(a-b-) phenotype (N = 42). Our data support the hypothesis that Le(a-b-) men exhibit features of the insulin resistance syndrome, including higher levels of BMI, SBP, and fasting levels of serum insulin and plasma glucose. In young women no signs of the insulin resistance syndrome were found in subjects with the Le(a-b-) phenotype.
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PMID:Lewis phenotypes and the insulin resistance syndrome in young healthy white men and women. 855 28

Previous studies have shown that high glucose levels and diabetes induce an elevation in protein kinase C (PKC) activity in vascular cells and tissues susceptible to diabetic complications. In addition, PKC activation has been shown to modulate vascular cell growth, permeability, and gene expression, processes thought to be involved in the development of vascular complications. Using two in vivo model systems, we have identified a novel inhibitor of diabetic vascular dysfunction, LY290181. LY290181 prevented glucose-induced increases in blood flow and permeability in rat granulation tissue and corresponding vascular changes in the retina, sciatic nerve, and aorta of diabetic rats. Tested for its ability to inhibit PKC-regulated processes, LY290181 inhibited phorbol ester-stimulated plasminogen activator activity in a dose-dependent manner in bovine retinal endothelial cells and in human dermal fibroblasts. In addition, LY290181 inhibited phorbol ester-stimulated activation of the porcine urokinase plasminogen activator (uPA) promoter (-4600/+398) linked to the chloramphenicol acetyltransferase (CAT) reporter gene (p4660CAT). More detailed analysis of the uPA promoter revealed that LY290181 inhibited phorbol ester-stimulated activation of the uPA phorbol response element (-2458/-2349) located upstream of the thymidine kinase promoter (puPATKCAT). LY290181 appears to inhibit uPA promoter activation by blocking phorbol ester-stimulated binding of nuclear proteins to the uPA PEA3/12-0-tetradecanoylphorbol 13-acetate responsive element (TRE). These results suggest that LY290181 may inhibit diabetes-induced vascular dysfunction by inhibiting transcription factor binding to specific PKC-regulated genes involved in vascular function.
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PMID:LY290181, an inhibitor of diabetes-induced vascular dysfunction, blocks protein kinase C-stimulated transcriptional activation through inhibition of transcription factor binding to a phorbol response element. 862 Oct 17

The associations between abdominal visceral fat and the plasma hemostatic system were examined in 38-year-old healthy men (n=52) with a wide range of fatness and fat distribution. Plasma hemostatic factors and metabolic parameters, including glucose tolerance, were measured, and body fatness and adipose tissue distribution were assessed by using computed tomography. The men with more visceral fat (ie, higher than the median value [n=26]) had a less favorable metabolic profile than the men with less visceral fat (n=26). They also had significantly (P<.05) higher plasma fibrinogen, factor VIII clotting activity, tissue-type plasminogen activator antigen, and plasminogen activator inhibitor-1 (PAI-1) activity (19.2+/-2.4 versus 8.5+/-1.6 AU/mL, P<.001) and lower basal tissue-type plasminogen activator activity. After adjustment for plasma insulin, the men with larger abdominal visceral fat area still had significantly higher plasma PAI-1 activity, but no difference was found in any of the other hemostatic factors. In multiple linear regression analysis, abdominal visceral fat area was a positive predictor of plasma PAI-1 activity, but it failed to show any significant association with other hemostatic factors after controlling for plasma insulin. These results suggest the presence of relationships between abdominal visceral fat and several plasma hemostatic factors that are largely mediated by concomitant alterations in plasma insulin concentration. In addition, our results suggest that abdominal accumulation of visceral fat is an independent predictor of plasma PAI-1 activity.
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PMID:Visceral fat accumulation and its relation to plasma hemostatic factors in healthy men. 863 Jun 61

This study assessed the short- and long-term effects of an energy-restrictive diet with or without exercise on plasminogen activator inhibitor-1 antigen (PAI-1 Ag) and PAI-1 activity, tissue-type plasminogen activator antigen (TPA Ag), and fibrinogen serum levels. Healthy, overweight postmenopausal women (age, 53.8+/-2.5 years; body mass index, 25 to 42 kg/m2; n=121) were randomly assigned to one of three groups: control, 4200-kJ/d diet, or 4200-kJ/d diet with combined aerobic and anaerobic exercise. PAI-1 activity and PAI-1 Ag, TPA Ag, and fibrinogen levels were measured at baseline, after a 12-week intervention, and after a further 6-month follow-up. PAI-1 Ag and activity and TPA Ag were positively correlated with serum triglyceride levels, the abdominal-to-total-body fat ratio (as assessed by total-body dual-energy x-ray absorptiometry), fasting blood glucose, and systolic BP and negatively with HDL cholesterol and sex hormone-binding globulin. The diet led to profound decreases and normalization of PAI-1 activity (approximately 50%), PAI-1 Ag (approximately 30%) and TPA Ag (approximately (29%), but exercise conferred no additional effect. Fibrinogen did not change. At follow-up there were no longer any significant changes (P>.05). In conclusion, PAI-1 Ag and activity as well as TPA Ag seem to be part of the metabolic syndrome X. The diet made the blood less thrombogenic in the short term with no effect of the added exercise.
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PMID:Plasminogen activator inhibitor-1, tissue-type plasminogen activator, and fibrinogen: Effect of dieting with or without exercise in overweight postmenopausal women. 863 Jun 63

In Denmark, clinicians conducted clinical and metabolic evaluations on 17 healthy women, 21-26 years old, within the last 10 days of their menstrual cycle preceding intake with a triphasic oral contraceptive (OC) (ethinyl estradiol + norgestimate) and during the last 7 days of the sixth period of OC treatment. They aimed to examine the effect of proinsulin and insulin on fasting secretion of plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (t-PA). OCs have a well-defined effect on plasma levels of PAI-1 and t-PA. The clinical researchers also studied the antigen concentrations of PAI-1 and t-PA during slow and fast changes in proinsulin and insulin levels induced by oral and intravenous glucose tolerance tests. They did not find consistent correlations between fasting values of proinsulin, insulin, PAI-1, and t-PA either before or during OC treatment. During the glucose tolerance test induced hyperproinsulinemia and hyperinsulinemia and before OC treatment, PAI-1 and t-PA antigen levels fell (p 0.05). After 6 months of OC treatment, t-PA levels fell only during the oral glucose tolerance test (p 0.05) even though proinsulin and insulin responded similarly to the glucose loads. These findings suggest that neither proinsulin nor insulin regulate plasma levels of PAI-1 and t-PA in young healthy women regardless of OC use status.
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PMID:No influence of proinsulin and insulin on plasma levels of plasminogen activator inhibitor type 1 and tissue plasminogen activator in young women before and during intake of contraceptive steroids. 869 17

Defibrotide, a polydeoxyribonucleotide, has been found to modulate endothelial cell function, causing an increase in tissue plasminogen activator (t-PA) levels, a decrease in plasminogen activator inhibitor (PAI) levels, and an increase in prostaglandin I2 (PGI2) formation in humans. Defibrotide has no direct anticoagulant effect but has a synergistic action with heparin. A strong antithrombotic effect has been observed in animal models. Thus, defibrotide has a beneficial effect in cases of deep venous thrombosis (DVT), peripheral obliterative vascular disorder (POVD), stroke, vasculitis, and thromboembolism. Defibrotide also inhibits platelet function and activation. A significant decrease in platelet aggregate formation on the suture line in microarterial anastomosis in rats is one way defibrotide can inhibit platelet function and activation. In humans, a slight prolongation' of the lag period in collagen-induced aggregation has been observed. In addition, a slight decrease in the maximum amplitude of the secondary wave of ADP and adrenalin-induced aggregations was also found. Platelet adhesion is diminished, the platelet differential count on formvar membrane is altered, and platelet aggregate formation is significantly inhibited. With an increase in platelet cyclic AMP (cAMP) content and a decrease in malonyl dialdehyde (MDA) and thromboxane B2 (TXB2) formation, the levels of platelet secretion products such as PF-4 and beta-thromboglobulin (beta-TG) in plasma decreased progressively. It was also demonstrated that the 14C-glucose transport defect of the platelet membrane of atherosclerotic patients was partially corrected with defibrotide treatment.
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PMID:Effect of defibrotide on platelet function. 880 24


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