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)

The present study was performed to elucidate the acute effect of insulin on levels of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor of endothelial cell type (PAI-1). Nine middle-aged, non-obese and non-smoking men were studied during a hyperinsulinemic, euglycemic glucose clamp for 2 h. Plasma insulin level during the clamp averaged 84 +/- 12 mU/l and euglycemia was maintained at 4.9 +/- 0.6 mmol/l. The t-PA activity gradually increased (75% mean increase after 2 h, p less than 0.001) and the PAI-1 activity decreased (49% mean decrease after 2 h, p less than 0.001) during the clamp. t-PA activity decreased and PAI-1 activity increased after the insulin infusion was ceased, but they were still 48% higher and 38% lower, respectively, after 60 min. PAI-1 and t-PA activities were not affected by saline infusion for 2 h. Thus, acute changes in the insulin levels lead to rapid alterations in the fibrinolytic system even when euglycemia is maintained. These effects may be induced by insulin itself or by the concomitant activation of the sympatho-adrenal system during the euglycemic clamp.
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PMID:The acute effect of insulin on tissue plasminogen activator and plasminogen activator inhibitor in man. 190 68

This study examined the effect of gliclazide on tissue-type plasminogen activator (t-PA)-related fibrinolysis in 23 Type I diabetic patients without residual beta-cell function and 17 Type II diabetic patients initially treated with tolbutamide. The Type I diabetic patients received gliclazide for a period of 6 months; the Type II diabetic patients were shifted from tolbutamide to gliclazide. In Type I diabetic patients, after 2-3 months of treatment with gliclazide, we observed a significant increase in plasma concentrations of total t-PA antigen that remained stable until discontinuation of the drug (p less than 0.0002), whereas the plasma concentrations of plasminogen activator inhibitor (PAI) did not change significantly during the study. Next, we investigated the possibility of gliclazide inducing t-PA-related fibrinolysis in a subset of Type II diabetics without detectable concentrations of t-PA during treatment with tolbutamide. The concentrations of active t-PA increased significantly 3 months after a change in treatment to gliclazide, and active t-PA again decreased in one patient to undetectable levels after 12 months with gliclazide. Moreover, the plasma concentrations of total t-PA antigen increased significantly (p less than 0.02) in this group of diabetic patients while PAI remained unchanged. The changes in t-PA-related fibrinolysis could not be related in either Type I or Type II diabetics to changes in metabolic state evaluated by blood glucose, HbA1c, cholesterol, triglycerides, or apolipoproteins A and B. We conclude that gliclazide has the potential to exert extrametabolic non-insulin-mediated effects on t-PA-related fibrinolysis in diabetic patients.
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PMID:Increased fibrinolytic potential induced by gliclazide in types I and II diabetic patients. 190 83

Aspergillus niger pectin lyases are encoded by a multigene family. The complete nucleotide sequence of the pectin lyase PLA-encoding gene pelA has been determined. Comparison of the deduced amino acid sequence with the deduced amino acid sequence of the other characterized pectin lyase, PLD, shows that the proteins share 69% amino acid identity. When grown on media with pectin as the sole carbon source, A. niger transformants containing multiple copies of the pelA gene show raised mRNA levels and overexpression of the gene product PLA compared with the wild-type strain. PLA was purified and characterized. In A. nidulans transformants PLA is also produced in medium containing a high concentration of glucose and no pectin.
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PMID:Structure of the Aspergillus niger pelA gene and its expression in Aspergillus niger and Aspergillus nidulans. 193 34

To investigate the coagulant and fibrinolytic potential of peritoneal macrophages, after short-term exposure to dialysis solutions intraperitoneal (IP) injection of these hyperosmolar glucose solutions was performed in rats. During the 72-hour postinjection period, the dialysis solutions and, as controls, Ringer's lactate and Ringer's lactate-glucose all induced a similar increase in the number of polymorphonuclear cells and macrophages within a maximum of 24 or 48 hours after their IP injection. These findings demonstrate that IP injection of any dialysis solution results in a moderate non-specific inflammatory cell harvesting. Compared with activity induced by the control solutions, no significant increase of procoagulant and fibrinolytic activities, identified respectively by the presence of thromboplastin and plasminogen activator, was observed in peritoneal macrophages obtained 48 hours after injection of the solution with the highest glucose concentration. However, the level of procoagulant activity could increase as a result of different manufacturers' processing of the solutions. That the basal level of macrophage functions may be modified suggests that this cell may initiate coagulolytic conditions in the peritoneal cavity, especially in the course of IP injection of dialysis solutions.
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PMID:Evaluation of macrophage procoagulant and fibrinolytic activities induced by peritoneal dialysis solutions. 200 76

An inadequate efficiency of the fibrinolytic system was revealed in 50-60% of subjects suffering young age from venous thrombosis or myocardial infarction. In a group of 27 patients with the history of deep venous thrombosis of the idiopathic type the authors revealed a significant relationship between the elevated body weight and inadequate fibrinolysis manifested by a reduced fibrinolytic capacity and excess inhibitor of plasminogen activator and its inadequate decline after desmopressin infusion (DDAVP). In a group of 29 patients, who had suffered a myocardial infarction when young, the authors revealed a significant association between reduced fibrinolytic capacity and elevated body weight, hypertriglyceridaemia and increased immunoreactive insulin secretion after a glucose load. In half the investigated subjects it proved possible to improve the reduced fibrinolytic capacity by a low energy diet.
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PMID:[Disorders of fibrinolysis and thrombophilic states, risk factors and possibilities of dietary effects]. 205 93

Cell lines established from the Lepidopteran insect Spodoptera frugiperda (e.g., Sf9) are used routinely as hosts for the expression of foreign proteins by baculovirus vectors. Previously, we showed that human tissue plasminogen activator (t-PA) was expressed, N-glycosylated, and secreted by Sf9 cells infected with a recombinant baculovirus (Jarvis DL, Summers MD: Mol Cell Biol 9:214-223, 1989). We also showed that t-PA secretion was blocked by tunicamycin (TM), an inhibitor of N-glycosylation, but not by castanospermine (CS) or N-methyldeoxynojirimycin, inhibitors of the initial steps in N-linked oligosaccharide processing. This suggested that the addition, but not the processing, of N-linked oligosaccharides is required for the secretion of recombinant t-PA from baculovirus-infected Sf9 cells. In this study, we present a more generalized evaluation of the role of N-glycosylation in the transport of recombinant glycoproteins through the Sf9 cell secretory pathway. Several different secretory or membrane-bound glycoproteins were expressed in control, TM-treated, or CS-treated Sf9 cells, and their appearance in the medium or on the cell surface was measured. The results showed that TM blocked the transport of some, but not all, of these proteins, whereas CS did not block the transport of any. This suggests that N-glycosylation is sometimes required for the transport of recombinant glycoproteins through the Sf9 secretory pathway, while processing of the oligosaccharides is not. At least two other proteins, p80 and p31, consistently coimmunoprecipitated with the nonglycosylated precursors of recombinant glycoproteins expressed in TM-treated Sf9 cells. Neither was antigenically related to any of the recombinant proteins. Relatively larger amounts of p80 and p31 were coprecipitated when transport was completely blocked by TM compared to when transport was only reduced or was unaffected. These results suggest that p80 and p31 block the transport of some nonglycosylated glycoprotein precursors in TM-treated Sf9 cells by binding to them and producing transport-incompetent heterooligomeric complexes. If this speculation is correct, then p80 and p31 are functionally analogous to the mammalian immunoglobulin heavy chain binding/glucose-regulated 78 kilodalton protein (BiP/GRP78).
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PMID:Role of glycosylation in the transport of recombinant glycoproteins through the secretory pathway of lepidopteran insect cells. 234 87

During treatment with tolbutamide 10 maturity onset diabetic patients had no detectable activity of tissue-type plasminogen activator (t-PA) determined on two occasions 3 months apart. All 10 patients responded on the change in treatment to gliclazide with an increase in activity of t-PA. However, after 12 months of treatment the t-PA activity in one of the 10 patients returned to the baseline level, whereas the remaining nine patients had a sustained increased t-PA activity compared to the period during treatment with tolbutamide. The concentration in plasma of t-PA antigen under basal conditions and after stimulation (venous occlusion) increased significantly during the period of treatment with gliclazide. The plasma concentrations of plasminogen activator inhibitor remained unchanged throughout the study. In contrast to these findings seven patients with marked activities of t-PA during treatment with tolbutamide retained unchanged levels of the variables reported above after a change in treatment to gliclazide. Serum glucose, HBA1c, apolipoproteins A and B, and triglycerides remained constant throughout the study, whereas serum cholesterol showed a decrease in both groups of patients after 3 months (P less than 0.05) as well as after 12 months (P less than 0.05) of treatment with gliclazide. There was no significant relationship between serum cholesterol concentrations and plasma concentrations of t-PA antigen indicating that the increase in t-PA antigen was independent of the metabolic state of the patients.
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PMID:Rise of plasma t-PA fibrinolytic activity in a group of maturity onset diabetic patients shifted from a first generation (tolbutamide) to a second generation sulphonylurea (gliclazide). 249 55

Treatment of the cells of the 311 cell line, a pluripotent mouse teratocarcinoma cell line, with 12-O-tetradecanoylphorbol-13-acetate (TPA) modulates c-mos expression. Transient suppression of 6.1 and 4.6 kilobases (kb) transcripts and activation of 1.8 transcript indicate that TPA mediates concurrently positive and negative regulation of c-mos transcription. The results show that the c-mos gene is a TPA-modulated gene. In addition, a TPA-responsive element (GTGACTCA), which exists in the 5'-flanking region of c-mos gene of Balb/c mice [1,2], is suggested to be involved in this response. However, these changes were not accompanied by early marker changes associated with endodermal cell differentiation, i.e., morphological change, induction of plasminogen activator and suppression of glucose transport activity.
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PMID:Changes of c-mos expression in response to 2-O-tetradecanoylphorbol-13-acetate in undifferentiated teratocarcinoma cells. 284 70

The treatment of 311 cells, a pluripotent mouse teratocarcinoma cell line, with a new type of inducer, 3,5-di-tert-butylchalcone 4'-carboxylic acid (Ch55), results in the suppression of the c-mos gene, accompanied by early marker changes associated with cell differentiation, i.e., the enhanced secretion of plasminogen activator and the decrease in peanut agglutinin receptors and glucose transport. This indicates that Ch55 is a potent inducer of teratocarcinoma cells and suppresses c-mos expression.
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PMID:Suppression of c-mos expression in teratocarcinoma cells with a new type of inducer of differentiation, 3,5-di-tert-butylchalcone 4'-carboxylic acid. 296 May 54

Functional abnormalities of tissue plasminogen activator (t-PA) (high Km in the presence of fibrin) and plasminogen (Pg) (substrate inhibition in the fibrin-stimulated system) from uncontrolled type I diabetics are reversible upon normalization of metabolic parameters. Therefore the effect of in vitro glucosylation of Pg was studied and similar but less pronounced substrate inhibition as with diabetic Pg was observed. However, the activation of the Pg fraction most likely containing bound cis-OH groups (e.g. glucose) was normal. These data suggest that either glucosylation in vitro is less stable than in vivo or that in diabetics protein modifications other than glucosylation occur. In this respect we can also show that acetone, a representative of ketone bodies and also elevated in poorly controlled diabetics, does not affect Pg activation in vitro.
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PMID:Plasminogen activation in diabetes mellitus. Kinetics of plasmin formation with tissue plasminogen activator and plasminogen from individual diabetic donors and with in vitro glucosylated plasminogen. 297 32


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