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Plasmin Activity (plasmin + activity)
Selected AbstractsPost-transcriptional regulation of plasminogen activator inhibitor-1 by intracellular iron in cultured human lung fibroblasts,interaction of an 81-kDa nuclear protein with the 3,-UTRJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2005K. S. RADHA Summary., The proteinase inhibitor, type-1 plasminogen activator inhibitor (PAI-1), is a major regulator of the plasminogen activator system involved in plasmin formation and fibrinolysis. The present study explores the effects of intracellular iron on the expression of PAI-1 and associated cell-surface plasmin activity in human lung fibroblasts; and reports the presence of a novel iron-responsive protein. ELISA revealed a dose-dependent increase in PAI-1 antigen levels expressed in the conditioned medium of cells treated with deferoxamine, in the three cell lines studied. A concomitant increase in mRNA levels was also observed by Northern analyses. Presaturation with ferric citrate quenched the effect of deferoxamine. Experiments with transcription and translation inhibitors on TIG 3-20 cells demonstrated that intracellular iron modulated PAI-1 expression at the post-transcriptional level with the requirement of de-novo protein synthesis. Electrophoretic mobility shift assay and UV crosslinking assays revealed the presence of an ,,81-kDa nuclear protein that interacted with the 3,-UTR of PAI-1 mRNA in an iron-sensitive manner. Finally, we demonstrated that the increased PAI-1 is functional in suppressing cell-surface plasmin activity, a process that can affect wound healing and tissue remodeling. [source] Estrogen-induced uterine abnormalities in TIMP-1 deficient mice are associated with elevated plasmin activity and reduced expression of the novel uterine plasmin protease inhibitor serpinb7MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 2 2009Xuan Zhang Abstract Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a multifunctional protein capable of regulating a variety of biological processes in a wide array of tissue and cell types. We have previously demonstrated that TIMP-1 deficient mice exhibit alterations in normal uterine morphology and physiology. Most notably, absence of TIMP-1 is associated with an altered uterine phenotype characterized by profound branching of the uterine lumen and altered adenogenesis. To begin to assess the mechanism by which TIMP-1 may control these uterine events, we utilized steroid-treated ovariectomized wild-type and TIMP-1 null mice exposed to estrogen for 72 hr. Administration of estrogen to TIMP-1 deficient mice resulted in development of an abnormal uterine histo-architecture characterized by increased endometrial gland density, luminal epithelial cell height, and abnormal lumen structure. To determine the mediators which may contribute to the abnormal uterine morphology in the TIMP-1 deficient mice, cDNA microarray analysis was performed. Analysis revealed that expression of two plasmin inhibitors (serpbinb2 and serbinb7) was significantly reduced in the TIMP-1 null mice. Associated with the reduction in expression of these inhibitors was a significant increase in plasmin activity. Localization of the novel uterine serpinb7 revealed that expression was confined to the luminal and glandular epithelial cells. Further, expression of uterine serpinb7 was decreased by estrogen and showed an inverse relationship with plasmin activity. We conclude from these studies that in addition to controlling MMP activity, TIMP-1 may also control activity of serine proteases through modulation of serine protease inhibitors such as serpinb7. Mol. Reprod. Dev. 76: 160,172, 2009. © 2008 Wiley-Liss, Inc. [source] Plasmin immunization preferentially induces potentially prothrombotic IgG anticardiolipin antibodies in MRL/MpJ miceARTHRITIS & RHEUMATISM, Issue 10 2009Kaleo Ede Objective To test the hypothesis, utilizing 2 experimental mouse models, that plasmin is an important autoantigen that drives the production of certain IgG anticardiolipin (aCL) antibodies in patients with the antiphospholipid syndrome. Methods BALB/cJ and MRL/MpJ mice were immunized with Freund's complete adjuvant in the presence or absence of human plasmin. The mouse sera were analyzed for production of IgG antiplasmin, IgG aCL, and IgG anti,,2 -glycoprotein I (anti-,2GPI) antibodies. IgG monoclonal antibodies (mAb) were generated from the plasmin-immunized MRL/MpJ mice with high titers of aCL, and these 10 mAb were studied for their binding properties and functional activity in vitro. Results Plasmin-immunized BALB/cJ mice produced high titers of IgG antiplasmin only, while plasmin-immunized MRL/MpJ mice produced high titers of IgG antiplasmin, IgG aCL, and IgG anti-,2GPI. Both strains of mice immunized with the adjuvant alone did not develop IgG antiplasmin or IgG aCL. All 10 of the IgG mAb bound to human plasmin and cardiolipin, while 4 of 10 bound to ,2GPI, 3 of 10 bound to thrombin, and 4 of 10 bound to the activated coagulation factor X (FXa). Functionally, 4 of the 10 IgG mAb inhibited plasmin activity, 1 of 10 hindered inactivation of thrombin by antithrombin III, and 2 of 10 inhibited inactivation of FXa by antithrombin III. Conclusion Plasmin immunization leads to production of IgG antiplasmin, aCL, and anti-,2GPI in MRL/MpJ mice, but leads to production of only IgG antiplasmin in BALB/cJ mice. IgG mAb generated from plasmin-immunized MRL/MpJ mice bind to various antigens and exhibit procoagulant activity in vitro. These results suggest that plasmin may drive potentially prothrombotic aCL in genetically susceptible individuals. [source] | ||||||||||