Gelatin in situ zymography on fixed, paraffin-embedded tissue: zinc and ethanol fixation preserve enzyme activity.
AuthorsHadler-Olsen E, Kanapathippillai P, Berg E, Svineng G, Winberg JO, Uhlin-Hansen L,
JournalJ Histochem Cytochem
PubMed ID19755718
In situ zymography is a method for the detection and localization of enzymatic activity in tissue sections. This method is used with frozen sections because routine fixation of tissue in neutral-buffered formalin inhibits enzyme activity. However, frozen sections present with poor tissue morphology, making precise localization of enzymatic activity difficult ... More
Chlorotoxin inhibits glioma cell invasion via matrix metalloproteinase-2.
AuthorsDeshane J, Garner CC, Sontheimer H
JournalJ Biol Chem
PubMed ID12454020
'Primary brain tumors (gliomas) have the unusual ability to diffusely infiltrate the normal brain thereby evading surgical treatment. Chlorotoxin is a scorpion toxin that specifically binds to the surface of glioma cells and impairs their ability to invade. Using a recombinant His-Cltx we isolated and identified the principal Cltx receptor ... More
Authentic matrix vesicles contain active metalloproteases (MMP). a role for matrix vesicle-associated MMP-13 in activation of transforming growth factor-beta.
AuthorsD'Angelo M, Billings PC, Pacifici M, Leboy PS, Kirsch T
JournalJ Biol Chem
PubMed ID11145962
'Matrix vesicles (MV) play a key role in the initiation of cartilage mineralization. Although many components in these microstructures have been identified, the specific function of each component is still poorly understood. In this study, we show that metalloproteases (MMP), MMP-2, -9, and -13 are associated with MV isolated from ... More
Effective antiprotease-antibiotic treatment of experimental anthrax.
'BACKGROUND: Inhalation anthrax is characterized by a systemic spread of the challenge agent, Bacillus anthracis. It causes severe damage, including multiple hemorrhagic lesions, to host tissues and organs. It is widely believed that anthrax lethal toxin secreted by proliferating bacteria is a major cause of death, however, the pathology of ... More
Molecular proximity of seprase and the urokinase-type plasminogen activator receptor on malignant melanoma cell membranes: dependence on beta1 integrins and the cytoskeleton.
'Previous studies have shown that several proteolytic enzymes are associated with membrane protrusions at the leading edge of migrating tumor cells. In this study we demonstrate that seprase and the urokinase plasminogen activator receptor (uPAR), co-localize in the plasma membrane of LOX malignant melanoma cells. Cells were labeled with fluorochrome-conjugated ... More
Pancreatic trypsin increases matrix metalloproteinase-9 accumulation and activation during acute intestinal ischemia-reperfusion in the rat.
AuthorsRosário HS, Waldo SW, Becker SA, Schmid-Schönbein GW
JournalAm J Pathol
PubMed ID15111317
'Ischemia-reperfusion of the intestine produces a set of inflammatory mediators, the origin of which has recently been shown to involve pancreatic digestive enzymes. Matrix metalloproteinase-9 (MMP-9) participates in a variety of inflammatory processes including myocardial, hepatic, and pancreatic ischemia-reperfusion. In the present study, we explore the role of neutrophil-derived MMP-9 ... More
Transthyretin, a new cryptic protease.
AuthorsLiz MA, Faro CJ, Saraiva MJ, Sousa MM
JournalJ Biol Chem
PubMed ID15033978
'Transthyretin (TTR) is a plasma homotetrameric protein that acts physiologically as a transporter of thyroxine (T(4)) and retinol, in the latter case through binding to retinol-binding protein (RBP). A fraction of plasma TTR is carried in high density lipoproteins by binding to apolipoprotein AI (apoA-I). We further investigated the nature ... More
Recombinant equine interleukin-1beta induces putative mediators of articular cartilage degradation in equine chondrocytes.
AuthorsTung JT, Fenton JI, Arnold C, Alexander L, Yuzbasiyan-Gurkan V, Venta PJ, Peters TL, Orth MW, Richardson DW, Caron JP,
JournalCan J Vet Res
PubMed ID11858644
'Interleukin-1 is considered a central mediator of cartilage loss in osteoarthritis in several species, however an equine recombinant form of this cytokine is not readily available for in vitro use in equine osteoarthritis research. Equine recombinant interleukin-1beta was cloned and expressed and its effects on the expression and activity of ... More
Role of exopolysaccharide, the rugose phenotype and VpsR in the pathogenesis of epidemic Vibrio cholerae.
AuthorsRashid MH, Rajanna C, Zhang D, Pasquale V, Magder LS, Ali A, Dumontet S, Karaolis DK
JournalFEMS Microbiol Lett
PubMed ID14734172
'Vibrio cholerae, the causative agent of cholera can produce an exopolysaccharide (EPS). Some strains can also phenotypically switch from a smooth to a ''rugose'' phenotype characterized by small wrinkled colonies, overproduction of EPS, increased biofilm formation in vitro and increased resistance to various stressful conditions. High frequency switching to the ... More
Transmembrane collagen XVII, an epithelial adhesion protein, is shed from the cell surface by ADAMs.
'Collagen XVII, a type II transmembrane protein and epithelial adhesion molecule, can be proteolytically shed from the cell surface to generate a soluble collagen. Here we investigated the release of the ectodomain and identified the enzymes involved. After surface biotinylation of keratinocytes, the ectodomain was detectable in the medium within ... More
S-nitrosylation of matrix metalloproteinases: signaling pathway to neuronal cell death.
AuthorsGu Z, Kaul M, Yan B, Kridel SJ, Cui J, Strongin A, Smith JW, Liddington RC, Lipton SA
JournalScience
PubMed ID12183632
'Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of neurodegenerative diseases and stroke. However, the mechanism of MMP activation remains unclear. We report that MMP activation involves S-nitrosylation. During cerebral ischemia in vivo, MMP-9 colocalized with neuronal nitric oxide synthase. S-Nitrosylation activated MMP-9 in vitro and induced neuronal apoptosis. Mass ... More
Metabolic mapping of proteinase activity with emphasis on in situ zymography of gelatinases: review and protocols.
AuthorsFrederiks WM, Mook OR
JournalJ Histochem Cytochem
PubMed ID15150280
'Proteases are essential for protein catabolism, regulation of a wide range of biological processes, and in the pathogenesis of many diseases. Several techniques are available to localize activity of proteases in tissue sections or cell preparations. For localization of the activity of matrix metalloproteinases, in situ zymography was introduced some ... More
Increased medial degradation with pseudo-aneurysm formation in apolipoprotein E-knockout mice deficient in tissue inhibitor of metalloproteinases-1.
AuthorsLemaître V, Soloway PD, D'Armiento J
JournalCirculation
PubMed ID12538437
'BACKGROUND: The tissue inhibitor of metalloproteinases-1 (TIMP-1) is expressed in atherosclerotic lesions, where it may play a critical role in regulating the activity of matrix metalloproteinases (MMPs). Several MMPs are overexpressed in the atherosclerotic plaque, and they are believed to contribute to the expansion and rupture of the lesion. METHODS ... More
In situ zymography and immunolabeling in fixed and decalcified craniofacial tissues.
AuthorsPorto IM, Rocha LB, Rossi MA, Gerlach RF,
JournalJ Histochem Cytochem
PubMed ID19188488
'In situ zymography is a very important technique that shows the proteolytic activity in sections and allows researchers to observe the specific sites of proteolysis in tissues or cells. It is normally performed in non-fixed frozen sections and is not routinely performed in calcified tissues. In this study, we describe ... More
EF domains are sufficient for nongenomic mineralocorticoid receptor actions.
AuthorsGrossmann C, Freudinger R, Mildenberger S, Husse B, Gekle M,
JournalJ Biol Chem
PubMed ID18184651
'The mineralocorticoid receptor (MR) is important for salt homeostasis and reno-cardiovascular pathophysiology. Signaling mechanisms include, besides classical genomic pathways, nongenomic pathways with putative pathophysiological relevance involving the mitogen-activated protein kinases ERK1/2. We determined the MR domains required for nongenomic signaling and their potential to elicit pathophysiological effects in cultured cells ... More
'Tissue inhibitors of metalloproteinases (TIMPs) are a family of multifunctional proteins known to possess a broad range of biological activities, including inhibition of metalloproteinase activity, regulation of proliferation and apoptosis of a variety of cell types, and, depending on the context, differential regulation of angiogenic and inflammatory responses. Elevated mRNA ... More
Requirement of matrix metalloproteinase-9 for the transformation of human mammary epithelial cells by Stat3-C.
AuthorsDechow TN, Pedranzini L, Leitch A, Leslie K, Gerald WL, Linkov I, Bromberg JF
JournalProc Natl Acad Sci U S A
PubMed ID15249664
Persistently activated Stat3 is found in many different cancers, including approximately 60% of breast tumors. Here, we demonstrate that a constitutively activated Stat3 transforms immortalized human mammary epithelial cells and that this oncogenic event requires the activity of matrix metalloproteinase-9 (MMP-9). By immunohistochemical analysis, we observe a positive correlation between ... More
Tyrosine kinase activity of discoidin domain receptor 1 is necessary for smooth muscle cell migration and matrix metalloproteinase expression.
AuthorsHou G, Vogel WF, Bendeck MP
JournalCirc Res
PubMed ID12065315
Smooth muscle cell (SMC) interactions with collagen mediate cell migration during the pathogenesis of atherosclerosis and restenosis. Discoidin domain receptors (DDRs) have been identified as novel collagen receptors. We used aortic SMCs from wild-type and DDR1(-/-) mice to evaluate the function of the DDR1 in regulating migration. DDR1(-/-) SMCs exhibited ... More
Activation of the Trk signaling pathway by extracellular zinc. Role of metalloproteinases.
AuthorsHwang JJ, Park MH, Choi SY, Koh JY
JournalJ Biol Chem
PubMed ID15659400
In certain brain regions, extracellular zinc concentrations can rise precipitously as intense neuronal activity releases large amounts of zinc from the nerve terminals. Although zinc release has been suggested to play a pathological role, its precise physiological effect is poorly understood. Here, we report that exposure to micromolar quantities of ... More
Matrix metalloproteinase-9 modulates intestinal injury in rats with transmural colitis.
AuthorsMedina C, Santana A, Paz MC, Díaz-Gonzalez F, Farre E, Salas A, Radomski MW, Quintero E,
JournalJ Leukoc Biol
PubMed ID16478919
Proteolysis and degradation of extracellular matrix by metalloproteinases (MMPs) may contribute to intestinal injury in inflammatory bowel disease. In the present study, we investigated the pathogenic role of gelatinases (MMP-9 and MMP-2) on transmural colonic injury in a rat model of chronic colitis, which was induced by intracolonic instillation of ... More
Selective modulation of matrix metalloproteinase 9 (MMP-9) functions via exosite inhibition.
Unregulated activities of the matrix metalloproteinase (MMP) family have been implicated in primary and metastatic tumor growth, angiogenesis, and pathological degradation of extracellular matrix components, such as collagen and laminin. However, clinical trials with small molecule MMP inhibitors have been largely unsuccessful, with a lack of selectivity considered particularly problematic. ... More
In vivo roles for matrix metalloproteinase-9 in mature hippocampal synaptic physiology and plasticity.
AuthorsBozdagi O, Nagy V, Kwei KT, Huntley GW,
JournalJ Neurophysiol
PubMed ID17493927
Extracellular proteolysis is an important regulatory nexus for coordinating synaptic functional and structural plasticity, but the identity of such proteases is incompletely understood. Matrix metalloproteinases (MMPs) have well-known, mostly deleterious roles in remodeling after injury or stroke, but their role in nonpathological synaptic plasticity and function in intact adult brains ... More
Gelatinolytic activity in atherosclerotic plaques is highly localized and is associated with both macrophages and smooth muscle cells in vivo.
AuthorsSegers D, Helderman F, Cheng C, van Damme LC, Tempel D, Boersma E, Serruys PW, de Crom R, van der Steen AF, Holvoet P, Krams R,
JournalCirculation
PubMed ID17242283
BACKGROUND: Atherosclerosis is considered an inflammatory disease. Recent studies provided evidence for a predominant upstream location of plaque inflammation. The present study introduces a novel technique that evaluates the underlying mechanism of this spatial organization. METHODS AND RESULTS: In hypercholesterolemic rabbits, atherosclerosis of the infrarenal aorta was induced by a ... More
Important role of matrix metalloproteinase 9 in epileptogenesis.
AuthorsWilczynski GM, Konopacki FA, Wilczek E, Lasiecka Z, Gorlewicz A, Michaluk P, Wawrzyniak M, Malinowska M, Okulski P, Kolodziej LR, Konopka W, Duniec K, Mioduszewska B, Nikolaev E, Walczak A, Owczarek D, Gorecki DC, Zuschratter W, Ottersen OP, Kaczmarek L,
JournalJ Cell Biol
PubMed ID18332222
Temporal lobe epilepsy (TLE) is a devastating disease in which aberrant synaptic plasticity plays a major role. We identify matrix metalloproteinase (MMP) 9 as a novel synaptic enzyme and a key pathogenic factor in two animal models of TLE: kainate-evoked epilepsy and pentylenetetrazole (PTZ) kindling-induced epilepsy. Notably, we show that ... More
Live-cell imaging demonstrates extracellular matrix degradation in association with active cathepsin B in caveolae of endothelial cells during tube formation.
Localization of proteases to the surface of endothelial cells and remodeling of the extracellular matrix (ECM) are essential to endothelial cell tube formation and angiogenesis. Here, we partially localized active cathepsin B and its cell surface binding partners, S100A/p11 (p11) of the annexin II heterotetramer (AIIt), to caveolae of human ... More
The biodegradability of electrospun Dextran/PLGA scaffold in a fibroblast/macrophage co-culture.
AuthorsPan H, Jiang H, Chen W,
JournalBiomaterials
PubMed ID18192003
Fibroblast and macrophage are 2 dominant cell types respond cooperatively to degrade implanted biomaterials. Using an electrospun Dextran/Poly-lactide-co-glycolide (PLGA) scaffold as a model, an in vitro fibroblast/macrophage co-culture system was developed to investigate the degradability of implantable biodegradable materials. SEM showed that both fibroblasts and macrophages were able to degrade ... More
Embolus extravasation is an alternative mechanism for cerebral microvascular recanalization.
AuthorsLam CK, Yoo T, Hiner B, Liu Z, Grutzendler J,
JournalNature
PubMed ID20505729
Cerebral microvascular occlusion is a common phenomenon throughout life that might require greater recognition as a mechanism of brain pathology. Failure to recanalize microvessels promptly may lead to the disruption of brain circuits and significant functional deficits. Haemodynamic forces and the fibrinolytic system are considered to be the principal mechanisms ... More
The membrane-anchored metalloproteinase regulator RECK stabilizes focal adhesions and anterior-posterior polarity in fibroblasts.
AuthorsMorioka Y, Monypenny J, Matsuzaki T, Shi S, Alexander DB, Kitayama H, Noda M,
JournalOncogene
PubMed ID19169281
Accumulating evidence indicates that Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a membrane-anchored matrix metalloproteinase regulator, plays crucial roles in mammalian development and tumor suppression. Its mechanisms of action at the single cell level, however, remain largely unknown. In mouse fibroblasts, RECK is abundant around the perinuclear region, membrane ruffles ... More
Cathepsin L is required for endothelial progenitor cell-induced neovascularization.
AuthorsUrbich C, Heeschen C, Aicher A, Sasaki K, Bruhl T, Farhadi MR, Vajkoczy P, Hofmann WK, Peters C, Pennacchio LA, Abolmaali ND, Chavakis E, Reinheckel T, Zeiher AM, Dimmeler S
JournalNat Med
PubMed ID15665831
Infusion of endothelial progenitor cells (EPC), but not of mature endothelial cells, promotes neovascularization after ischemia. We performed gene expression profiling of EPC and endothelial cells to identify genes that might be important for the neovascularization capacity of EPC. Notably, the protease cathepsin L (CathL) was highly expressed in EPC ... More
Matrix metalloproteinase-9/gelatinase B is required for process outgrowth by oligodendrocytes.
Oligodendrocytes (OLs) extend processes to contact axons as a prerequisite step in myelin formation. As the OL processes migrate toward their axonal targets, they modify adhesion to their substrate, an event that may be regulated by matrix metalloproteinases (MMPs). In the mouse optic nerve, MMP-9/gelatinase B increases during myelin formation. ... More
Thrombospondin-1 suppresses spontaneous tumor growth and inhibits activation of matrix metalloproteinase-9 and mobilization of vascular endothelial growth factor.
AuthorsRodriguez-Manzaneque JC, Lane TF, Ortega MA, Hynes RO, Lawler J, Iruela-Arispe ML
JournalProc Natl Acad Sci U S A
PubMed ID11606713
Growth of tumors and metastasis are processes known to require neovascularization. To ascertain the participation of the endogenous angiogenic inhibitor thrombospondin-1 (TSP1) in tumor progression, we generated mammary tumor-prone mice that either lack, or specifically overexpress, TSP1 in the mammary gland. Tumor burden and vasculature were significantly increased in TSP1-deficient ... More
Deficiency in matrix metalloproteinase gelatinase B (MMP-9) protects against retinal ganglion cell death after optic nerve ligation.
AuthorsChintala SK, Zhang X, Austin JS, Fini ME
JournalJ Biol Chem
PubMed ID12354772
Loss of retinal ganglion cells is the final end point in blinding diseases of the optic nerve such as glaucoma. To enable the use of mouse genetics to investigate mechanisms underlying ganglion cell loss, we adapted an experimental model of optic nerve ligation to the mouse and further characterized post-surgical ... More
In situ localization of gelatinolytic activity in the extracellular matrix of metastases of colon cancer in rat liver using quenched fluorogenic DQ-gelatin.
AuthorsMook OR, Van Overbeek C, Ackema EG, Van Maldegem F, Frederiks WM
JournalJ Histochem Cytochem
PubMed ID12754293
Matrix metalloproteinases (MMPs) such as gelatinases are believed to play an important role in invasion and metastasis of cancer. In this study we investigated the possible role of MMP-2 and MMP-9 in an experimental model of colon cancer metastasis in rat liver. We demonstrated with gelatin zymography that the tumors ... More
Secreted MMP9 promotes angiogenesis more efficiently than constitutive active MMP9 bound to the tumor cell surface.
AuthorsMira E, Lacalle RA, Buesa JM, de Buitrago GG, Jiménez-Baranda S, Gómez-Moutón C, Martínez-A C, Mañes S
JournalJ Cell Sci
PubMed ID15075244
Association of matrix metalloprotease 9 (MMP9) to the cell membrane is considered important in tumor growth and angiogenesis. To dissect this regulatory mechanism, we generated raft and non-raft MMP9 chimeras to force membrane expression in the MCF-7 human breast carcinoma cell line. MMP9 targeting to non-raft cell surface domains rendered ... More
Cortical spreading depression activates and upregulates MMP-9.
AuthorsGursoy-Ozdemir Y, Qiu J, Matsuoka N, Bolay H, Bermpohl D, Jin H, Wang X, Rosenberg GA, Lo EH, Moskowitz MA
JournalJ Clin Invest
PubMed ID15146242
Cortical spreading depression (CSD) is a propagating wave of neuronal and glial depolarization and has been implicated in disorders of neurovascular regulation such as stroke, head trauma, and migraine. In this study, we found that CSD alters blood-brain barrier (BBB) permeability by activating brain MMPs. Beginning at 3-6 hours, MMP-9 ... More
In vivo evidence for active matrix metalloproteinases in human endometrium supports their role in tissue breakdown at menstruation.
AuthorsZhang J, Salamonsen LA
JournalJ Clin Endocrinol Metab
PubMed ID11994386
Human endometrium remodels extensively during each reproductive cycle culminating in loss of most functionalis tissue at menstruation. Evidence suggests that menstruation results from the action of the matrix metalloproteinases (MMP), enzymes secreted in latent forms. MMP activation is thus an important regulatory step. It has not been established that MMPs ... More
Matrix metalloproteinase (2, 9, and 14) expression, localization, and activity in ovine corpora lutea throughout the estrous cycle.
AuthorsRicke WA, Smith GW, Reynolds LP, Redmer DA, Smith MF
JournalBiol Reprod
PubMed ID11906929
Members of the matrix metalloproteinase (MMP) family collectively degrade extracellular matrix (ECM) and help regulate luteal function. The objectives of these experiments were to characterize the mRNA expression, localization, and activity of MMPs 2, 9, and 14 in ovine corpora lutea (CL). Ovine CL were collected on Days 2, 4, ... More
Nanoliter homogenous ultra-high throughput screening microarray for lead discoveries and IC50 profiling.
AuthorsMa H, Horiuchi KY, Wang Y, Kucharewicz SA, Diamond SL
JournalAssay Drug Dev Technol
PubMed ID15871692
Microfluidic technologies offer the potential for highly productive and low-cost ultra-high throughput screening and high throughput selectivity profiling. Such technologies need to provide the flexibility of plate-based assays as well as be less expensive to operate. Presented here is a unique microarray system (the Reaction Biology [Malvern, PA] DiscoveryDot), which ... More
Pressure-induced matrix metalloproteinase-9 contributes to early hypertensive remodeling.
AuthorsLehoux S, Lemarié CA, Esposito B, Lijnen HR, Tedgui A
JournalCirculation
PubMed ID14967734
BACKGROUND: High blood pressure causes a change in vascular wall structure involving altered extracellular matrix composition, but how this process occurs is not fully understood. METHODS AND RESULTS: Using mouse carotid arteries maintained in organ culture for 3 days, we detected increased gelatin zymographic activity of matrix metalloproteinase (MMP)-2 (168+/-13%, ... More
Matrix metalloproteinase-9 is required for hippocampal late-phase long-term potentiation and memory.
AuthorsNagy V, Bozdagi O, Matynia A, Balcerzyk M, Okulski P, Dzwonek J, Costa RM, Silva AJ, Kaczmarek L, Huntley GW
JournalJ Neurosci
PubMed ID16481424
Matrix metalloproteinases (MMPs) are extracellular proteases that have well recognized roles in cell signaling and remodeling in many tissues. In the brain, their activation and function are customarily associated with injury or pathology. Here, we demonstrate a novel role for MMP-9 in hippocampal synaptic physiology, plasticity, and memory. MMP-9 protein ... More
Signaling through the EGF receptor controls lung morphogenesis in part by regulating MT1-MMP-mediated activation of gelatinase A/MMP2.
AuthorsKheradmand F, Rishi K, Werb Z
JournalJ Cell Sci
PubMed ID11865039
Epithelial-mesenchymal interactions during lung development require extracellular signaling factors that facilitate branching morphogenesis. We show here that matrix metalloproteinases (MMPs) originating in the mesenchyme are necessary for epithelial branching and alveolization. We found that the delayed lung maturation characterized by abnormal branching and poor alveolization seen in mice deficient in ... More
Secreted neutral metalloproteases of Bacillus anthracis as candidate pathogenic factors.
To evaluate the pathogenic potential of Bacillus anthracis-secreted proteases distinct from lethal toxin, two neutral zinc metalloproteases were purified to apparent homogeneity from the culture supernatant of a non-virulent delta Ames strain (pXO1-, pXO2-). The first (designated Npr599) is a thermolysin-like enzyme highly homologous to bacillolysins from other Bacillus species. ... More
Overexpression of the serine elastase inhibitor elafin protects transgenic mice from hypoxic pulmonary hypertension.
AuthorsZaidi SH, You XM, Ciura S, Husain M, Rabinovitch M
JournalCirculation
PubMed ID11815437
BACKGROUND: Increased serine elastase activity has been implicated in the vascular remodeling associated with chronic hypoxia-related pulmonary hypertension in rats. METHODS AND RESULTS: In this study we determined the time course of hypoxia-induced serine elastase activity in the murine lung and related this to initiation of a proteolytic cascade characterized ... More
Hyperoxia-induced emphysematous changes in subacute phase of endotoxin-induced lung injury in rats.
AuthorsKohno M, Ishizaka A, Sawafuji M, Koh H, Hirayama Y, Ikeda E, Shiomi T, Ohashi A, Okada Y, Kobayashi K
JournalAm J Physiol Lung Cell Mol Physiol
PubMed ID15003927
We examined the effects of prolonged hyperoxia (75% O(2)) on lung structure and collagen metabolism in the subacute phase of lung injury induced by continuous infusion of endotoxin (LPS) in a rat model. Experimental groups included control, endotoxin alone, endotoxin plus hyperoxia, and hyperoxia alone. Endotoxin-treated rats received a bolus ... More
Matrix metalloproteinase-9 degrades amyloid-beta fibrils in vitro and compact plaques in situ.
AuthorsYan P, Hu X, Song H, Yin K, Bateman RJ, Cirrito JR, Xiao Q, Hsu FF, Turk JW, Xu J, Hsu CY, Holtzman DM, Lee JM
JournalJ Biol Chem
PubMed ID16787929
The pathological hallmark of Alzheimer disease is the senile plaque principally composed of tightly aggregated amyloid-beta fibrils (fAbeta), which are thought to be resistant to degradation and clearance. In this study, we explored whether proteases capable of degrading soluble Abeta (sAbeta) could degrade fAbeta as well. We demonstrate that matrix ... More
Mast cell tissue inhibitor of metalloproteinase-1 is cleaved and inactivated extracellularly by alpha-chymase.
AuthorsFrank BT, Rossall JC, Caughey GH, Fang KC
JournalJ Immunol
PubMed ID11160345
We previously reported that mast cell alpha-chymase cleaves and activates progelatinase B (progel B). Outside of cells, progel B is complexed with tissue inhibitor of metalloproteinase (TIMP)-1, which hinders zymogen activation and inhibits activity of mature forms. The current work demonstrates that dog BR mastocytoma cells, HMC-1 cells, and murine ... More