Search results for "Proteinase"
showing 10 items of 407 documents
Urokinase Plasminogen Activator and Gelatinases Are Associated with Membrane Vesicles Shed by Human HT1080 Fibrosarcoma Cells
1997
Membrane vesicles are shed by tumor cells both in vivo and in vitro. Although their functions are not well understood, it has been proposed that they may play multiple roles in tumor progression. We characterized membrane vesicles from human HT1080 fibrosarcoma cell cultures for the presence of proteinases involved in tumor invasion. By gelatin zymography and Western blotting, these vesicles showed major bands corresponding to the zymogen and active forms of gelatinase B (MMP-9) and gelatinase A (MMP-2) and to the MMP-9. tissue inhibitor of metalloproteinase 1 complex. Both gelatinases appeared to be associated with the vesicle membrane. HT1080 cell vesicles also showed a strong, plasminoge…
Liver-specific overexpression of matrix metalloproteinase 9 (MMP-9) in transgenic mice accelerates development of hepatocellular carcinoma.
2010
Matrix metalloproteinase-9 (MMP-9) plays a central role in tumor invasion and development of metastases. Expression of MMP-9 had been shown in human hepatocellular carcinomas (HCCs). However, it remained unclear whether MMP-9 could influence development of HCC. In order to address this issue, we generated transgenic mice overexpressing MMP-9 in the liver. In order to avoid embryonic lethality a Cre-lox system was utilized for conditional overexpression of MMP-9 under control of an albumin enhancer and promoter. Induction of MMP-9 overexpression in transgenic mice was achieved by i.v. injection of an adenovirus coding for the Cre recombinase. Initiation of liver carcinogenesis was achieved b…
Placental endogenous retrovirus (ERV): structural, functional, and evolutionary significance
1998
Summary That endogenous retrovirus (ERV) is present within the placenta of humans and other mammals has been known for the past 25 years, but the significance of this observation is still not fully understood. Much molecular biological data have emerged in recent years to support the earlier electron microscopic data on the presence of placental ERV. The evidence for ERV in animal and human placental tissue is presented, then integrated with data on the the presence of ERV in a range of other tissues, in particular teratocarcinoma cells. Placental invasiveness and maternal immunosuppression are then discussed in relation to metalloproteinase secretion, the immunosuppressive potential of ret…
Redox regulation of genome stability by effects on gene expression, epigenetic pathways and DNA damage/repair
2015
Reactive oxygen and nitrogen species (e.g. H2O2, nitric oxide) confer redox regulation of essential cellular signaling pathways such as cell differentiation, proliferation, migration and apoptosis. In addition, classical regulation of gene expression or activity, including gene transcription to RNA followed by translation to the protein level, by transcription factors (e.g. NF-κB, HIF-1α) and mRNA binding proteins (e.g. GAPDH, HuR) is subject to redox regulation. This review will give an update of recent discoveries in this field, and specifically highlight the impact of reactive oxygen and nitrogen species on DNA repair systems that contribute to genomic stability. Emphasis will be placed …
Role of the Netrin-like Domain of Procollagen C-Proteinase Enhancer-1 in the Control of Metalloproteinase Activity
2010
The netrin-like (NTR) domain is a feature of several extracellular proteins, most notably the N-terminal domain of tissue inhibitors of metalloproteinases (TIMPs), where it functions as a strong inhibitor of matrix metalloproteinases and some other members of the metzincin superfamily. The presence of a C-terminal NTR domain in procollagen C-proteinase enhancers (PCPEs), proteins that stimulate the activity of astacin-like tolloid proteinases, raises the possibility that this might also have inhibitory activity. Here we show that both long and short forms of the PCPE-1 NTR domain, the latter beginning at the N-terminal cysteine known to be critical for TIMP activity, show no inhibition, at …
Maturation of barley cysteine endopeptidase expressed in Trichoderma reesei is distorted by incomplete processing
2002
Maturation of barley cysteine endopeptidase B (EPB) in Trichoderma reesei was studied with metabolic inhibitors, Western blotting, and immuno microscopy. The inactive 42-kDa recombinant EPB proprotein, first detected in apical cells, was sequentially processed in a time-dependent manner to a secreted polypeptide of 38.5 kDa, and thereafter, to polypeptides of 37.5, 35.5, and 32 kDa exhibiting enzyme activity both in the hyphae and culture medium. The sizes of the different forms of recombinant EPB were in accordance with molecular masses calculated from the deduced amino acid sequence, assuming cleavage at four putative Kex2p sites present in the 42-kDa proprotein. Both the liquid and the z…
Activation of a caspase-3-independent mode of cell death associated with lysosomal destabilization in cultured human retinal pigment epithelial cells…
2008
International audience; Purpose: To characterize the possible cytotoxic effects of oxysterols (7-hydroxycholesterol (7-OH), 25-hydroxycholesterol (25-OH)) in human retinal pigment epithelial cells (ARPE-19) and to detail the relationships between some of these effects. Methods: ARPE-19 cells were treated with 7-OH and 25-OH. Cell viability was measured with the MTT assay. Membrane permeability, mitochondrial potential, and lysosomal integrity were measured by flow cytometry with propidium iodide, DiOC6(3), and acridine orange, respectively. Cell death was characterized by staining with Hoechst 33342, transmission electron microscopy, and analysis of the DNA fragmentation pattern. Caspase ac…
Fluorine Scan of Inhibitors of the Cysteine Protease Human Cathepsin L: Dipolar and Quadrupolar Effects in the π-Stacking of Fluorinated Phenyl Rings…
2016
The π-stacking of fluorinated benzene rings on protein backbone amide groups was investigated, using a dual approach comprising enzyme-ligand binding studies complemented by high-level quantum chemical calculations. In the experimental study, the phenyl substituent of triazine nitrile inhibitors of human cathepsin L (hCatL), which stacks onto the peptide amide bond Gly67-Gly68 at the entrance of the S3 pocket, was systematically fluorinated, and differences in inhibitory potency were measured in a fluorimetric assay. Binding affinity is influenced by lipophilicity (clog P), the dipole and quadrupole moments of the fluorinated rings, but also by additional interactions of the introduced fluo…
Stefin A and cathepsin B and L circulating serum levels in patients with malignant or non-malignant liver diseases: A preliminary report
1995
Experimental and clinical studies have recently shown a significant correlation between increased activity levels of lysosomal proteinases Cathepsin B, L in tumor tissues and malignant progression. On the basis of these findings we have undertaken some preliminary studies to evaluate the clinical impact of these enzymes and their intracellular inhibitor Stefin A in patients with malignant and non malignant liver diseases. The serum levels of Cathepsin B, L and Stefin A resulted significantly increased (mean 7 folds) in patients with liver diseases as compared to healthy subjects . these findings suggest that Cathepsin B, Cathepsin L, and Stefin A serum levels may be potentially useful as pr…
Macrophage MerTK promotes profibrogenic cross-talk with hepatic stellate cells via soluble mediators
2022
Background & aims: Activation of Kupffer cells and recruitment of monocytes are key events in fibrogenesis. These cells release soluble mediators which induce the activation of hepatic stellate cells (HSCs), the main fibrogenic cell type within the liver. Mer tyrosine kinase (MerTK) signaling regulates multiple processes in macrophages and has been implicated in the pathogenesis of non-alcoholic steatohepatitis-related fibrosis. In this study, we explored if MerTK activation in macrophages influences the profibrogenic phenotype of HSCs. Methods: Macrophages were derived from THP-1 cells or differentiated from peripheral blood monocytes towards MerTK+/CD206+/CD163+/CD209- macrophages. Th…