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norskBlar i forfatter Det helsevitenskapelige fakultet "Winberg, Jan-Olof"
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Biosynthesis of Promatrix Metalloproteinase-9/Chondroitin Sulphate Proteoglycan Heteromer Involves a Rottlerin-Sensitive Pathway
(Journal article; Tidsskriftartikkel; Peer reviewed, 2011)Background: Previously we have shown that a fraction of the matrix metalloproteinase-9 (MMP-9) synthesized by the macrophage cell line THP-1 was bound to a chondroitin sulphate proteoglycan (CSPG) core protein as a reduction sensitive heteromer. Several biochemical properties of the enzyme were changed when it was bound to the CSPG. <br>Methodology/Principal Findings: By use of affinity chromatography, ... -
Cancer-associated fibroblasts from human NSCLC survive ablative doses of radiation but their invasive capacity is reduced
(Journal article; Tidsskriftartikkel; Peer reviewed, 2012)BACKGROUND: Cancer-Associated Fibroblasts (CAFs) are significant components of solid malignancies and play central roles in cancer sustainability, invasion and metastasis. In this study we have investigated the invasive capacity and matrix remodelling properties of human lung CAFs after exposure to ablative doses of ionizing radiation (AIR), equivalent to single fractions delivered by stereotactic ... -
The catalytic reaction mechanism of drosophilid alcohol dehydrogenases
(Journal article; Tidsskriftartikkel; Peer reviewed, 2014-12-24)The present review describes the current knowledge about the reaction mechanism of drosophilid alcohol dehydrogenases (DADH), a member of the short chain dehydrogenase/reductase (SDR) superfamily. Included is the binding order of the substrates to the enzyme, rate limiting steps, stereochemistry of the reaction, active site topology, role of important amino acids and water molecules in the reaction ... -
Characterization and pro-inflammatory responses of spore and hyphae samples from various mold species
(Journal article; Tidsskriftartikkel; Manuskript; Peer reviewed; Preprint, 2017-09-18)Mold particles from <i>Aspergillus fumigatus, Penicillium chrysogenum, Aspergillus versicolor</i>, and <i>Stachybotrys chartarum</i> have been linked to respiratory‐related diseases. We characterized X‐ray‐inactivated spores and hyphae fragments from these species by number of particles, morphology, and mycotoxin, β‐glucan and protease content/activity. The pro‐inflammatory properties of mold particles ... -
Cleavage of the urokinase receptor (uPAR) on oral cancer cells: Regulation by transforming growth factor - beta1 (TGF-beta1) and potential effects on migration and invasion
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-05-19)Background: Urokinase plasminogen activator (uPA) receptor (uPAR) is up-regulated at the invasive tumour front of human oral squamous cell carcinoma (OSCC), indicating a role for uPAR in tumour progression. We previously observed elevated expression of uPAR at the tumour-stroma interface in a mouse model for OSCC, which was associated with increased proteolytic activity. The tumour microenvironment ... -
Inhibition of bacterial and human zinc-metalloproteases by bisphosphonate- and catechol-containing compounds
(Journal article; Tidsskriftartikkel; Peer reviewed, 2021-03-23)Compounds containg catechol or bisphosphonate were tested as inhibitors of the zinc metalloproteases, thermolysin (TLN), pseudolysin (PLN) and aureolysin (ALN) which are bacterial virulence factors, and the human matrix metalloproteases MMP-9 and −14. Inhibition of virulence is a putative strategy in the development of antibacterial drugs, but the inhibitors should not interfere with human enzymes. ... -
Inhibition of chemerin/CMKLR1 axis in neuroblastoma cells reduces clonogenicity and cell viability in vitro and impairs tumor growth in vivo
(Journal article; Tidsskriftartikkel; Peer reviewed, 2017-07-27)Pro-inflammatory cells, cytokines, and chemokines are essential in promoting a tumor supporting microenvironment. Chemerin is a chemotactic protein and a natural ligand for the receptors CMKLR1, GPR1, and CCRL2. The chemerin/CMKLR1 axis is involved in immunity and inflammation, and it has also been implicated in obesity and cancer.<p> In neuroblastoma, a childhood tumor of the peripheral nervous ... -
Intracellular MMP-2 Activity in Skeletal Muscle is Associated with Type II Fibers
(Journal article; Tidsskriftartikkel; Peer reviewed, 2014-09-29)Matrix metalloproteinase 2 (MMP-2) is a proteolytic enzyme implicated in motility, differentiation, and regeneration of skeletal muscle fibers through processing of extracellular substrates. Although MMP-2 has been found to be localized intracellularly in cardiomyocytes where the enzyme is thought to contribute to post-ischemic loss of contractility, little is known about intracellular MMP-2 activity ... -
Matrix metalloproteinases in subjects with type 1 diabetes
(Journal article; Tidsskriftartikkel; Peer reviewed, 2009-09-16)Background: Nephropathy is serious complication of diabetes. We have previously shown that level of the proteoglycan syndecan-1 in blood is associated with ultrastructural kidney changes in young persons with type 1 diabetes. Dysregulation of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) may contribute to the development of nephropathy. The aim of ... -
Method for Determining Gelatinolytic Activity in Tissue Extracts: Real-Time Gelatin Zymography
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019)To explore the physiological or pathological roles of proteases, it is important to be able to detect and precisely localize them in a tissue, to differentiate between inactive and active forms, as well as to quantify and determine the nature of the enzyme that degrades a given substrate. Here we present a protocol for real-time gelatin zymography that is very useful for the detection of gelatin-degrading ... -
Method for Determining Gelatinolytic Activity in Tissue: In Situ Gelatin Zymography
(Journal article; Tidsskriftartikkel; Peer reviewed, 2019)To explore the physiological or pathological roles of proteases, it is important to be able to detect and precisely localize them in a tissue, to differentiate between inactive and active forms, as well as to quantify and determine the nature of the enzyme that degrades a given substrate. Here we present an in situ gelatin zymography method that allows for a precise localization of active gelatin-degrading ... -
Molecular Interactions Stabilizing the Promatrix Metalloprotease-9·Serglycin Heteromer
(Journal article; Tidsskriftartikkel; Peer reviewed, 2020-06-12)Previous studies have shown that THP-1 cells produced an SDS-stable and reduction-sensitive complex between proMMP-9 and a chondroitin sulfate proteoglycan (CSPG) core protein. The complex could be reconstituted in vitro using purified serglycin (SG) and proMMP-9 and contained no inter-disulfide bridges. It was suggested that the complex involved both the FnII module and HPX domain of proMMP-9. The ... -
Proteases in plasma and kidney of db /db mice as markers of diabetes-induced nephropathy
(Journal article; Tidsskriftartikkel; Peer reviewed, 2011)Db/db mice are overweight, dyslipidemic and develop diabetic complications, relevant for similar complications in human type 2 diabetes. We have used db/db and db/+ control mice to investigate alterations in proteinase expression and activity in circulation and kidneys by SDS-PAGE zymography, electron microscopy, immunohistochemistry, Western blotting, and in situ zymography. Plasma from db/db mice ... -
The selectivity of galardin and an azasugar-based hydroxamate compound for human Matrix metalloproteases and bacterial metalloproteases
(Journal article; Tidsskriftartikkel; Peer reviewed, 2018-08-03)Inhibitors targeting bacterial enzymes should not interfere with enzymes of the host, and knowledge about structural determinants for selectivity is important for designing inhibitors with a therapeutic potential. We have determined the binding strengths of two hydroxamate compounds, galardin and compound 1b for the bacterial zinc metalloproteases, thermolysin, pseudolysin and auerolysin, known to ... -
Stromal impact on tumor growth and lymphangiogenesis in human carcinoma xenografts
(Journal article; Tidsskriftartikkel; Peer reviewed, 2010) -
Synthesis, experimental evaluation and molecular modelling of hydroxamate derivatives as zinc metalloproteinase inhibitors
(Journal article; Tidsskriftartikkel; Peer reviewed, 2015-11-28)Enzymes of the M4 family of zinc-metalloproteinases are virulence factors secreted from gram-positive or gram-negative bacteria, and putative drug targets in the treatment of bacterial infections. In order to have a therapeutic value such inhibitors should not interfere with endogenous zinc-metalloproteinases. In the present study we have synthesised a series of hydroxamate derivatives and validated ... -
Tumour Microenvironments Induce Expression of Urokinase Plasminogen Activator Receptor (uPAR) and Concomitant Activation of Gelatinolytic Enzymes
(Journal article; Tidsskriftartikkel; Peer reviewed, 2014) -
Zinc-Chelating Compounds as Inhibitors of Human and Bacterial Zinc Metalloproteases
(Journal article; Tidsskriftartikkel; Peer reviewed, 2021-12-22)Inhibition of bacterial virulence is believed to be a new treatment option for bacterial infections. In the present study, we tested dipicolylamine (DPA), tripicolylamine (TPA), tris pyridine ethylene diamine (TPED), pyridine and thiophene derivatives as putative inhibitors of the bacterial virulence factors thermolysin (TLN), pseudolysin (PLN) and aureolysin (ALN) and the human zinc metalloproteases, ...
