Search results for "plasminogen"

Urokinase activates macrophage PON2 gene transcription via the PI3K/ROS/MEK/SREBP-2 signalling cascade mediated by the PDGFR-β

2009

Aims We have recently shown that urokinase plasminogen activator (uPA) increases oxidative stress (OS), cholesterol biosynthesis, and paraoxonase 2 (PON2) expression in macrophages via binding to its receptor, the uPAR. Since PON2 is regulated by both OS and cholesterol content, we hypothesized that uPA elicits a cascade of signal transduction events shared by NADPH oxidase and cholesterol biosynthesis that culminates in PON2 gene expression. Here, we investigated the signalling pathway that leads to the expression of PON2 in macrophages in response to uPA. Methods and results The increase in macrophage PON2 mRNA levels in response to uPA was shown to depend on PON2 gene promoter activation…

Nonradical oxidants of the phagocyte type induce the activation of plasmatic single chain- urokinase

1991

Single chain- urokinase (scu-PA) is the proenzyme of the plasminogen activator urokinase (tcu-PA). In human blood scu-PA is of great stability. Activated phagocytes generate large amounts of single chain- urokinase and of reactive oxidants (chloramines and HOCl). Since these cells participate in physiologic fibrinolysis, we were interested in the interaction between plasmatic scu-PA and chloramines. The oxidants dose dependently induce the activation of plasmatic scu-PA. Optimal activation of scu-PA occurs at about 3-5 mmol/l of chloramine-T. The findings suggest a control mechanism of scu-PA stability/activity by oxidatively modifiable plasma proteins, such as alpha-2-antiplasmin. The oxid…

Ligneous Cervicitis in a Woman With Plasminogen Deficiency Associated With an Atypical Form of Microglandular Hyperplasia

2013

A 19-yr-old woman with previously diagnosed clear cell adenocarcinoma was referred to the Charité for further treatment. Biopsies were taken from the cervix, the endometrium, pseudomembranes in the peritoneum, and sentinel lymph nodes. The morphologic picture of pseudomembranes and inflammation together with the provided information about plasminogen deficiency of the patients led to the hypothesis of ligneous cervicitis. The previously taken biopsies of the adenocarcinoma were reevaluated and showed a clear cell lesion. Further immunohistochemical examination with antibodies against p16, Ki67, CEA, and p53 could not prove its malignant character. As a result we diagnosed an atypical form o…

Anti-ETAR and suPAR as markers of disease activity in renal ANCA-associated vasculitis.

2020

Purpose In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), there is a lack of reliable biomarkers of disease activity. The aim of the study was to evaluate soluble urokinase plasminogen activator receptor (suPAR) and anti-endothelin-1 type A receptor (anti-ETAR) antibodies levels in active phase and remission of AAV. Patients and methods We enrolled 60 patients (median age 63.0 years) with renal AAV into this study. Plasma suPAR, urine suPAR (expressed as urine suPAR/creatinine ratio) and serum anti-ETAR antibodies were assayed by ELISA. Disease activity was assessed using Birmingham Vasculitis Activity Score (BVAS) and patients were divided into 2 subgroups based o…

Kondrat'eva ligation: Diels-Alder-based irreversible reaction for bioconjugation.

2014

International audience; Diversification of existing chemoselective ligations is required to efficiently access complex and well-defined biomolecular assemblies with unique and valuable properties. The development and bioconjugation applications of a novel Diels-Alder-based irreversible site-specific ligation are reported. The strategy is based on a Kondrat'eva cycloaddition between bioinert and readily functionalizable 5-alkoxyoxazoles and maleimides that readily react together under mild and easily tunable reaction conditions to afford a fully stable pyridine scaffold. The potential of this novel bioconjugation is demonstrated through the preparation of fluorescent conjugates of biomolecul…

Cytotoxicity of the Urokinase-Plasminogen Activator Inhibitor Carbamimidothioic Acid (4-Boronophenyl) Methyl Ester Hydrobromide (BC-11) on Triple-Neg…

2015

BC-11 is an easily synthesized simple thiouronium-substituted phenylboronic acid, which has been shown to be cytotoxic on triple negative MDA-MB231 breast cancer cells by inducing a perturbation of cell cycle when administered at a concentration equal to its ED50 at 72 h (117 μM). Exposure of cells to BC-11, either pre-absorbed with a soluble preparation of the N-terminal fragment of urokinase-plasminogen activator (uPa), or in co-treatment with two different EGFR inhibitors, indicated that: (i) BC-11 acts via binding to the N-terminus of the enzyme where uPa- and EGF receptor-recognizing sites are present, thereby abrogating the growth-sustaining effect resulting from receptor binding

Treatment of Hereditary Angioedema with the Mutation c.988A>G (p.K330E) in the Plasminogen Gene

2020

Cross-over study on effects of Mediterranean diet in two randomly selected population samples

2003

Abstract Two randomly selected population samples in Western Sicily, one rural (n = 40) and one urban (n = 40), were studied to evaluate the impact of dietary intervention on lipid, coagulative and fibrinolytic parameters. The two groups received the diets in a cross-over design with the following sequences: (a) baseline period; (b) 8-week dietary intervention period; (c) 8-week return to the original diet. During (a) and (c) all subjects consumed their usual diet. During the dietary intervention period (b), the rural sample consumed the urban sample's diet, while the urban sample consumed the rural sample's diet (the so-called “Mediterranean diet”). At baseline, after 8 weeks' dietary inte…

Evaluation of PAI-1 in endometriosis using a homologous immunocompetent mouse model

2018

To analyze the role of PAI-1 (plasminogen activator inhibitor 1) in endometriotic lesion growth, we studied the effect of PAI-1 inhibition by PAI-039 using a homologous mouse model of endometriosis that allows noninvasive monitoring. Endometrial tissue from donor mice was collected, labeled with mCherry adenovirus, and implanted into a subcutaneous pocket on the ventral abdomen of recipient mice. Seven days after transplantation, mice were randomly allocated in two groups and treated once daily for 2 weeks with either vehicle (control group) or PAI-1 inhibitor (PAI-039 group). Endometriotic lesion size generated in recipient mice was monitored by mCherry signal. Animals were euthanized 21 d…

Advancing stem cells: New therapeutic strategies for treating central nervous system disorders

2018

In this special issue, we explore new methods and knowledge to improve stem cell transplantation in diseases and conditions such as stroke, PD, and depression. Advancing the conventional idea regarding cell replacement in stem cell therapy, stem cells may also transfer healthy mitochondria to diseased ischemic neurons in stroke and improve the therapeutic time window of tissue plasminogen activator (tPA) in a conjunctive therapy for stroke, and human Wharton’s Jelly-derived mesenchymal stromal cells (hWJ-MSCs) may rely mainly on trophic factor secretion to induce neuroprotective effects. In addition, trophic factors such as neurotrophin-4/5 (NT-4/5) and glial cell line-derived neurotrophic …