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 authors examined the effect of insulin-like growth factor 1 (IGF 1), epidermal growth factor (EGF), and acidic fibroblast growth factor (AFGF) on the synthesis by human retinal endothelial cell (HREC) of plasminogen activators (PA; tissue-type [t-PA] and urokinase-type [u-PA]) and plasminogen activator inhibitor (PAI). Immunologic and functional assays for t-PA, u-PA, and PA1 were conducted with cell lines derived from three diabetics and three nondiabetic controls. Confluent HREC of nondiabetic origin did not respond to IGF I (100 ng/ml) with any change of t-PA antigen in the medium (10.7 +/- 1.1 ng/ml unstimulated versus 10.1 +/- 0.8 ng/ml) stimulated, P = not significant). Likewise AFGF and EGF caused no significant change of t-PA levels. Both IGF I and EGF caused a significant increase of t-PA from HREC of diabetic origin (9.6 +/- 0.8 ng/ml unstimulated versus 16.6 +/- 1.9 ng/ml IGF I-stimulated, P less than 0.001, and 14.6 +/- 2.7 ng/ml EGF-stimulated P less than 0.005). Supplementation of AFGF had no effect on HREC of diabetic origin. In confluent cultures, only small quantities of u-PA were detected. After wounding confluent cultures, u-PA activity was associated with cells migrating from the wound edges. Functional PA activity was also measured by chromogenic assay. Results further supported a predominance of t-PA activity being produced by confluent HREC in culture. These results suggest that modulation of PA production by HREC is influenced by exposure to growth factors, by the state of confluency, and the origin of the cells (diabetic vesus nondiabetic).
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PMID:Plasminogen activator production by human retinal endothelial cells of nondiabetic and diabetic origin. 170 73

Human rTNF/Cachectin was shown to stimulate gene transcription of plasminogen activator inhibitor (PA1)-1 and PAI-2, and simultaneously suppress constitutive gene expression of tissue-type plasminogen activator (t-PA) in human fibrosarcoma cells. We propose that a TNF-mediated reprogramming of gene transcription induces, in appropriate target cells, an anti-fibrinolytic state, which may cooperate with the induction of procoagulant activity (tissue factor) to stabilize the fibrin deposits commonly found in inflamed tissue. PAI genes also provide a model system for a study of the molecular pathways underlying TNF-mediated signal transduction.
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PMID:Plasminogen activator inhibitor 1 and 2 are tumor necrosis factor/cachectin-responsive genes. 313 5

Because recent information suggests that the localized deposition of protease inhibitors is one mechanism by which cells regulate pericellular proteolysis during tissue invasion, the distribution of type 1 plasminogen activator inhibitor (PA1-1) associated with the invasive human glioma cell line U-251 was investigated. Direct and reverse fibrin zymography indicated the presence of urokinase-like plasminogen activator (u-PA) and PAI-1 in U-251 conditioned media and cell lysates. PA1-1 antigen was detected immunologically in cytoplasmic granules present within cellular processes of U-251 cells and these organelles could be isolated on Percoll density gradients in a high density band. In contrast, u-PA activity and another secreted protein, amyloid beta-protein precursor, were only present in the low density region of the gradients. Functional analysis of PAI-1 in the granules contained within the high density fractions revealed the presence of active PAI-1. Incubation of U-251 cells with the secretagogue, 8-bromoadenosine 3':5'-cyclic monophosphate, resulted in a 3-fold increase in the release of PAI-1 in the media conditioned by these cells. These data suggest that the human glioma cell line U-251 contains PAI-1 in a rapidly releasable form, which may provide another mechanism by which these tumors could regulate proteolytic activity in a localized manner.
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PMID:Human glioma U-251 cells contain type 1 plasminogen activator inhibitor in a rapidly releasable form. 881 93

We studied the influence of age on mortality and severity of clotting abnormalities in 79 children (median age: 3.1 years) with meningococcal sepsis. Parameters of coagulation and fibrinolysis and plasma levels of cytokines were prospectively measured on admission. The mortality rate was 27%. The age of survivors was significantly different from that of non-survivors (p = 0.013). With the exception of FVII, vWF and t-PA, parameters of coagulation and fibrinolysis, as well as plasma cytokine levels were related to outcome. Patients were divided in two groups: younger and older than median age. The mortality in children < or = 3.1 years was 40% versus 13% in children > 3.1 years (p = 0.006). In contrast to cytokine levels, which were not different between the two age groups, fibrinogen, prothrombin, factors V, VII, VIII, vWF, protein C, antithrombin, FDP, and the ratio PA1-1/t-PA were related to age, indicating a more severe coagulopathy in children < or = 3.1 years despite a similar degree of inflammatory response. A relative deficiency of coagulation factors due to an immature state of the clotting system, as well as an inadequate fibrinolytic response, both related to age may have caused this more severe coagulative response in younger children, and may have contributed to the higher mortality rate.
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PMID:Age-related differences in outcome and severity of DIC in children with septic shock and purpura. 897 13

We report here that human astrocytoma cell line U373-MG is able to express genes of the following components of plasminogen activation system: PA1-1, PN-1, u-PA and t-PA. Treatment of these cells with IL-1beta results in accumulation of PA1-1, PN-1 and u-PA mRNAs, whereas t-PA mRNA remains unaffected. IFNy preferentially enhances PN-1 and PA1-1, EGF enhances PA1-1, u-PA and t-PA expression. Simultaneous addition of anti-inflammatory cytokines IL-4, IL-13 and IL-10 has little effect on the tested components, except induction of u-PA mRNA wich was further enhanced by IL-4. We have confirmed interesting time-dependent regulation of plasminogen activation system by EGF/IFNgamma. Cells stimulated with EGF/IFNgamma show at first increased proteolytic activity but after 24 h inhibition of proteolysis with PA1-1 would prevail. To understand the cooperative effect of EGF and IFNgamma in PA1-1 induction the kinetics of activation of STAT1 was studied. It was found that although EGF alone does not activate STAT1, the STAT1 binding activity in the cells treated with the mixture of EGF/IFNgamma was considerably prolonged. Our results indicate the importance of inflammatory cytokines and EGF in gene regulation of plasminogen activation system in astrocytoma cells.
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PMID:Cytokines regulate plasminogen activation system in astrocytoma cells. 1193 22