A family of neutral serine proteases with CHYMOTRYPSIN-like activity. Chymases are primarily found in the SECRETORY GRANULES of MAST CELLS and are released during mast cell degranulation.
A family of neutral serine proteases with TRYPSIN-like activity. Tryptases are primarily found in the SECRETORY GRANULES of MAST CELLS and are released during mast cell degranulation.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the BASOPHILS, mast cells contain large amounts of HISTAMINE and HEPARIN. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the STEM CELL FACTOR.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.
Endopeptidases that are specific for AMYLOID PROTEIN PRECURSOR. Three secretase subtypes referred to as alpha, beta, and gamma have been identified based upon the region of amyloid protein precursor they cleave.
A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.
Glands of external secretion that release its secretions to the body's cavities, organs, or surface, through a duct.
A family of the order Rodentia containing 250 genera including the two genera Mus (MICE) and Rattus (RATS), from which the laboratory inbred strains are developed. The fifteen subfamilies are SIGMODONTINAE (New World mice and rats), CRICETINAE, Spalacinae, Myospalacinae, Lophiomyinae, ARVICOLINAE, Platacanthomyinae, Nesomyinae, Otomyinae, Rhizomyinae, GERBILLINAE, Dendromurinae, Cricetomyinae, MURINAE (Old World mice and rats), and Hydromyinae.
A complication of PREGNANCY, characterized by a complex of symptoms including maternal HYPERTENSION and PROTEINURIA with or without pathological EDEMA. Symptoms may range between mild and severe. Pre-eclampsia usually occurs after the 20th week of gestation, but may develop before this time in the presence of trophoblastic disease.
Organizations established by endowments with provision for future maintenance.
The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.
The morning glory family of flowering plants, of the order Solanales, which includes about 50 genera and at least 1,400 species. Leaves are alternate and flowers are funnel-shaped. Most are twining and erect herbs, with a few woody vines, trees, and shrubs.
Individuals licensed to practice medicine.
Attitudes of personnel toward their patients, other professionals, toward the medical care system, etc.
An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.
A peptidyl-dipeptidase that catalyzes the release of a C-terminal dipeptide, -Xaa-*-Xbb-Xcc, when neither Xaa nor Xbb is Pro. It is a Cl(-)-dependent, zinc glycoprotein that is generally membrane-bound and active at neutral pH. It may also have endopeptidase activity on some substrates. (From Enzyme Nomenclature, 1992) EC 3.4.15.1.
Benzoic acids, salts, or esters that contain an amino group attached to carbon number 2 or 6 of the benzene ring structure.
Damages to the CAROTID ARTERIES caused either by blunt force or penetrating trauma, such as CRANIOCEREBRAL TRAUMA; THORACIC INJURIES; and NECK INJURIES. Damaged carotid arteries can lead to CAROTID ARTERY THROMBOSIS; CAROTID-CAVERNOUS SINUS FISTULA; pseudoaneurysm formation; and INTERNAL CAROTID ARTERY DISSECTION. (From Am J Forensic Med Pathol 1997, 18:251; J Trauma 1994, 37:473)
Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery.
The innermost layer of an artery or vein, made up of one layer of endothelial cells and supported by an internal elastic lamina.
Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.
Enlargement of the LEFT VENTRICLE of the heart. This increase in ventricular mass is attributed to sustained abnormal pressure or volume loads and is a contributor to cardiovascular morbidity and mortality.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Cellulose derivative used in chromatography, as ion-exchange material, and for various industrial applications.
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.
Immunoglobulins induced by antigens specific for tumors other than the normally occurring HISTOCOMPATIBILITY ANTIGENS.
Antibodies produced by a single clone of cells.
The most abundant protein component of HIGH DENSITY LIPOPROTEINS or HDL. This protein serves as an acceptor for CHOLESTEROL released from cells thus promoting efflux of cholesterol to HDL then to the LIVER for excretion from the body (reverse cholesterol transport). It also acts as a cofactor for LECITHIN CHOLESTEROL ACYLTRANSFERASE that forms CHOLESTEROL ESTERS on the HDL particles. Mutations of this gene APOA1 cause HDL deficiency, such as in FAMILIAL ALPHA LIPOPROTEIN DEFICIENCY DISEASE and in some patients with TANGIER DISEASE.
A class of lipoproteins of small size (4-13 nm) and dense (greater than 1.063 g/ml) particles. HDL lipoproteins, synthesized in the liver without a lipid core, accumulate cholesterol esters from peripheral tissues and transport them to the liver for re-utilization or elimination from the body (the reverse cholesterol transport). Their major protein component is APOLIPOPROTEIN A-I. HDL also shuttle APOLIPOPROTEINS C and APOLIPOPROTEINS E to and from triglyceride-rich lipoproteins during their catabolism. HDL plasma level has been inversely correlated with the risk of cardiovascular diseases.
Amino acids containing an aromatic side chain.
All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from BIOLOGY, one of its subdivisions, concerned specifically with the origin and life processes of living organisms.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
Messages between computer users via COMPUTER COMMUNICATION NETWORKS. This feature duplicates most of the features of paper mail, such as forwarding, multiple copies, and attachments of images and other file types, but with a speed advantage. The term also refers to an individual message sent in this way.
An endopeptidase that is structurally similar to MATRIX METALLOPROTEINASE 2. It degrades GELATIN types I and V; COLLAGEN TYPE IV; and COLLAGEN TYPE V.
A secreted endopeptidase homologous with INTERSTITIAL COLLAGENASE, but which possesses an additional fibronectin-like domain.
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
A member of the family of TISSUE INHIBITOR OF METALLOPROTEINASES. It is a N-glycosylated protein, molecular weight 28 kD, produced by a vast range of cell types and found in a variety of tissues and body fluids. It has been shown to suppress metastasis and inhibit tumor invasion in vitro.
Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.
A genus of short-tailed OPOSSUMS in the family Didelphidae found in South American, chiefly Brazil. They are opossums least well-adapted to arboreal life.
A serine protease found in the azurophil granules of NEUTROPHILS. It has an enzyme specificity similar to that of chymotrypsin C.
New World marsupials of the family Didelphidae. Opossums are omnivorous, largely nocturnal and arboreal MAMMALS, grow to about three feet in length, including the scaly prehensile tail, and have an abdominal pouch in which the young are carried at birth.
A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissues. They function optimally within an acidic pH range. The cathepsins occur as a variety of enzyme subtypes including SERINE PROTEASES; ASPARTIC PROTEINASES; and CYSTEINE PROTEASES.
A species of the genus FLAVIVIRUS which causes an acute febrile and sometimes hemorrhagic disease in man. Dengue is mosquito-borne and four serotypes are known.
An acute febrile disease transmitted by the bite of AEDES mosquitoes infected with DENGUE VIRUS. It is self-limiting and characterized by fever, myalgia, headache, and rash. SEVERE DENGUE is a more virulent form of dengue.
A virulent form of dengue characterized by THROMBOCYTOPENIA and an increase in vascular permeability (grades I and II) and distinguished by a positive pain test (e.g., TOURNIQUET PAIN TEST). When accompanied by SHOCK (grades III and IV), it is called dengue shock syndrome.
A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system.
Proteins, protein complexes, or glycoproteins secreted by suppressor T-cells that inhibit either subsequent T-cells, B-cells, or other immunologic phenomena. Some of these factors have both histocompatibility (I-J) and antigen-specific domains which may be linked by disulfide bridges. They can be elicited by haptens or other antigens and may be mass-produced by hybridomas or monoclones in the laboratory.

Tranilast suppresses vascular chymase expression and neointima formation in balloon-injured dog carotid artery. (1/553)

BACKGROUND: Activation of vascular chymase plays a major role in myointimal hypertrophy after vascular injury by augmenting the production of angiotensin (ANG) II. Because chymase is synthesized mainly in mast cells, we assumed that the chymase-dependent ANG II formation could be downregulated by tranilast, a mast cell-stabilizing antiallergic agent. We have assessed inhibitory effects of tranilast on neointima formation after balloon injury in the carotid artery of dogs, which share a similar ANG II-forming chymase with humans, and further explored the pathophysiological significance of vascular chymase. METHODS AND RESULTS: Either tranilast (50 mg/kg BID) or vehicle was orally administered to beagles for 2 weeks before and 4 weeks after balloon injury. Four weeks after the injury, remarkable neointima was formed in the carotid arteries of vehicle-treated dogs. Chymase mRNA levels and chymaselike activity of vehicle-treated injured arteries were increased 10.2- and 4.8-fold, respectively, those of uninjured arteries. Angiotensin-converting enzyme (ACE) activity was slightly increased in the injured arteries, whereas ACE mRNA levels were not. Tranilast treatment completely prevented the increase in chymaselike activity, reduced the chymase mRNA levels by 43%, and decreased the carotid intima/media ratio by 63%. In vehicle-treated injured arteries, mast cell count in the adventitia showed a great increase, which was completely prevented by the tranilast treatment. Vascular ACE activity and mRNA levels were unaffected by tranilast. CONCLUSIONS: Tranilast suppressed chymase gene expression, which was specifically activated in the injured arteries, and prevented neointima formation. Suppression of the chymase-dependent ANG II-forming pathway may contribute to the beneficial effects of tranilast.  (+info)

Lack of effect of carbohydrate depletion on some properties of human mast cell chymase. (2/553)

Human chymase from vascular tissues was purified to homogeneity by heparin affinity and gel filtration chromatography. Treatment of human chymase with endoglycosidase F resulted in cleavage of the carbohydrate moiety yielding a deglycosylation product that did not lose its catalytic activity. This enzymatic deglycosylation product was enough to explore possibilities that N-glycan might modify some properties of human chymase. Substrate specificity, optimum pH and the elution profile from the heparin affinity gel were not affected by the deglycosylation. Only a slight but significant difference was observed in the Km value for conversion of angiotensin I to angiotensin II. Other kinetic constants such as kcat were not influenced. The kinetics of conversion of big endothelin-1 to endothelin-1(1-31) were not significantly affected. The deglycosylated human chymase was more susceptible to deactivation under alkaline pH and thermal stress. Even at physiological temperature and pH, the activity of glycosylated human chymase was more stable. From these results, it appears that the N-glycan of human chymase contributes to the stability of this enzyme but not to its functional properties.  (+info)

Induction of atherosclerosis in Brown Norway rats by immunization with ovalbumin. (3/553)

A study was carried out to establish an animal model that would be suitable for evaluating the role of the diet in immune cell-mediated atherogenesis. Brown Norway rats were initially treated with hypervitamin D2 for 4 days and then fed on an atherogenic diet for 3 months, during which period the rats were either immunized with ovalubumin plus Al(OH)3 (OVA group) or with Al(OH)3 alone (control group) every 3 weeks. Aortic lesions were mainly composed of foam cells, the lesions evaluated by the intimal thickness of the ascending aorta being more severe in the OVA group than in the control group. The OVA group, in comparison with the control group, showed prominently increased serum levels of OVA-specific IgG and rat chymase, an indicator of mast cell degranulation. The intimal thickness was positively correlated with the level of chymase. Immunization had no effect on the serum lipid levels. These results support the hypothesis that mast cells play a role in the early stage of atherosclerosis and suggest that this animal model could be useful for evaluating the role of the diet in immune-related atherogenesis.  (+info)

Fibroproliferation and mast cells in the acute respiratory distress syndrome. (4/553)

BACKGROUND: Mast cells (MCs), which are a major source of cytokines and growth factors, have been implicated in various fibrotic disorders. To clarify the contribution of MCs to fibrogenesis, lung tissue from patients with the acute respiratory distress syndrome (ARDS) was examined during exudative through to fibroproliferative stages. METHODS: Lung tissue was obtained from 17 patients with ARDS who had pathological features of the early exudative stage (n = 6) or the later reparative stages (n = 11), from four patients with idiopathic pulmonary fibrosis, and from three patients with normal lung tissue. Immunohistochemical localisation of tryptase (found in all human MCs), chymase (found in a subset of human MCs), alpha-smooth muscle actin (identifies myofibroblasts), and procollagen type I was performed. RESULTS: Normal lung tissue exhibited myofibroblast and procollagen type I immunolocalisation scores each of < 5 and MC scores of 1. Increased scores were defined as myofibroblast and procollagen type I scores of > 10 and MC scores of > or = 2. Eighty percent of lung tissue samples from the early exudative stage of ARDS exhibited increased numbers of myofibroblasts, 50% had increased numbers of procollagen type I producing cells, while only 17% had increased numbers of MCs compared with control samples. All samples from the later reparative stages of ARDS had increased numbers of myofibroblasts and procollagen type I producing cells. Increased numbers of MCs were seen in 55% of samples from the reparative stages. There was no significant shift in MC phenotype in the ARDS samples. CONCLUSIONS: Increased numbers of myofibroblasts and procollagen type I producing cells were frequently found early in the course of ARDS. MC hyperplasia was unusual during this stage, but was often a feature of the later reparative stages. MCs do not appear to initiate fibroproliferation in ARDS.  (+info)

Depletion of pre beta 1LpA1 and LpA4 particles by mast cell chymase reduces cholesterol efflux from macrophage foam cells induced by plasma. (5/553)

Exposure of the LpA1-containing particles present in HDL3 and plasma to a minimal degree of proteolysis by the neutral protease chymase from exocytosed rat mast cell granules (granule remnants) leads to a reduction in the high-affinity component of cholesterol efflux from macrophage foam cells. In this study, we demonstrate for the first time, a role for mast cell chymase in the depletion of the lipid-poor minor components of HDL that are specifically involved in reverse cholesterol transport as initial acceptors of cellular cholesterol. Thus, addition of proteolytically active granule remnants or human skin chymase to cholesterol-loaded macrophages of mouse or human origin incubated with human apoA1, ie, a system in which prebeta1LpA1 is generated, resulted in a sharp reduction in the high-affinity cholesterol efflux promoted by apoA1. As determined by nondenaturing 2-dimensional polyacrylamide gradient gel electrophoresis, the granule remnants effectively depleted the prebeta1LpA1, but not the alphaLpA1, in HDL3 and in plasma during incubation at 37 degrees C for <1 hour. Incubation of plasma with granule remnants for 1 hour also led to near disappearance of the LpA4-1 and LpA4-2 particles, but did not affect the distribution of the apoA2-containing lipoproteins present in the plasma. We conclude that the reduced ability of granule remnant-treated HDL3 and granule remnant-treated plasma to induce cholesterol efflux from macrophage foam cells is caused by selective depletion by mast cell chymase of quantitatively minor A1- and A4-containing subpopulations of HDL. Because these particles, ie, prebeta1LpA1 and LpA4, are efficient acceptors of cholesterol from cell surfaces, their depletion by mast cells may block the initiation of reverse cholesterol transport in vivo and thereby favor foam cell formation in the arterial intima, the site of atherogenesis.  (+info)

Mast cell expression of gelatinases A and B is regulated by kit ligand and TGF-beta. (6/553)

Our prior work shows that cultured BR cells derived from dog mastocytomas secrete the 92-kDa proenzyme form of gelatinase B. We provided a possible link between mast cell activation and metalloproteinase-mediated matrix degradation by demonstrating that alpha-chymase, a serine protease released from secretory granules by degranulating mast cells, converts progelatinase B to an enzymatically active form. The current work shows that these cells also secrete gelatinase A. Furthermore, gelatinases A and B both colocalize to alpha-chymase-expressing cells of canine airway, suggesting that normal mast cells are a source of gelatinases in the lung. In BR cells, gelatinase B and alpha-chymase expression are regulated, whereas gelatinase A expression is constitutive. Progelatinase B mRNA and enzyme expression are strongly induced by the critical mast cell growth factor, kit ligand, which is produced by fibroblasts and other stromal cells. Induction of progelatinase B is blocked by U-73122, Ro31-8220, and thapsigargin, implicating phospholipase C, protein kinase C, and Ca2+, respectively, in the kit ligand effect. The profibrotic cytokine TGF-beta virtually abolishes the gelatinase B mRNA signal and also attenuates kit ligand-mediated induction of gelatinase B expression, suggesting that an excess of TGF-beta in inflamed or injured tissues may alter mast cell expression of gelatinase B, which is implicated in extracellular matrix degradation, angiogenesis, and apoptosis. In summary, these data provide the first evidence that normal mast cells express gelatinases A and B and suggest pathways by which their regulated expression by mast cells can influence matrix remodeling and fibrosis.  (+info)

A novel function for transforming growth factor-beta1: upregulation of the expression and the IgE-independent extracellular release of a mucosal mast cell granule-specific beta-chymase, mouse mast cell protease-1. (7/553)

Intestinal mucosal mast cells (IMMC) express granule neutral proteases that are regulated by T-cell-derived cytokines, including interleukin-3 (IL-3) and IL-9, and by stem cell factor (SCF). The IMMC-specific chymase, mouse mast cell protease-1 (mMCP-1), is released in substantial quantities into the blood stream during gastrointestinal allergic responses. We used cultured bone marrow-derived mast cells (mBMMC) to identify cytokines that regulate the expression and extracellular release of mMCP-1. When grown in IL-3-rich WEHI (15% vol/vol) and 50 ng/mL recombinant rat SCF (rrSCF) bone marrow cells supplemented with IL-9 (5 ng/mL) differentiated into mBMMC that expressed a maximum of less than 250 ng mMCP-1/10(6) cells and 189 ng mMCP-1/mL of culture supernatant. Supplementation of the same three cytokines with transforming growth factor-beta1 (TGF-beta1; 1 ng/mL) resulted in substantially enhanced expression (6 micrograms/10(6) mBMMC) and extracellular release (2 micrograms/mL of culture supernatant) of mMCP-1. The response to TGF-beta1 was dose-dependent, with maximal effect at 1 ng/mL, and was associated with immunohistochemical and ultrastructural changes in the secretory granules. IL-9-induced expression of mMCP-1 may be due to endogenously expressed TGF-beta1, because it was blocked by anti-TGF-beta antibodies. In conclusion, the expression and extracellular release of the IMMC-specific chymase, mMCP-1, is strictly regulated by TGF-beta1.  (+info)

Evidence for angiotensin-converting enzyme- and chymase-mediated angiotensin II formation in the interstitial fluid space of the dog heart in vivo. (8/553)

BACKGROUND: We have previously demonstrated that angiotensin II (Ang II) levels in the interstitial fluid (ISF) space of the heart are higher than in the blood plasma and do not change after systemic infusion of Ang I. In this study, we assess the enzymatic mechanisms (chymase versus ACE) by which Ang II is generated in the ISF space of the dog heart in vivo. METHODS AND RESULTS: Cardiac microdialysis probes were implanted in the left ventricular (LV) myocardium (3 to 4 probes per dog) of 12 anesthetized open-chest normal dogs. ISF Ang I and II levels were measured at baseline and during ISF infusion of Ang I (15 micromol/L, n=12), Ang I+the ACE inhibitor captopril (cap) (2.5 mmol/L, n=4), Ang I+the chymase inhibitor chymostatin (chy) (1 mmol/L, n=4), and Ang I+cap+chy (n=4). ISF infusion of Ang I increased ISF Ang II levels 100-fold (P<0.01), whereas aortic and coronary sinus plasma Ang I and II levels were unaffected and were 100-fold lower than ISF levels. Compared with ISF infusion of Ang I alone, Ang I+cap (n=4) produced a greater reduction in ISF Ang II levels than did Ang I+chy (n=4) (71% versus 43%, P<0.01), whereas Ang I+cap+chy produced a 100% decrease in ISF Ang II levels. CONCLUSIONS: This study demonstrates for the first time a very high capacity for conversion of Ang I to Ang II mediated by both ACE and chymase in the ISF space of the dog heart in vivo.  (+info)

Immune cells like NK cells, T cells, neutrophils and mast cells store high amounts of granule serine proteases, graspases. Graspases are encoded from the mast cell chymase locus. The human locus holds four genes: α-chymase, cathepsin G, and granzymes H and B. In contrast, the mouse locus contains at least 14 genes. Many of these belong to subfamilies not found in human, e.g. the Mcpt8-family. These differences hamper functional comparisons of graspases and of immune cells in the two species. Studies of the mast cell chymase locus are therefore important to better understand the mammalian immune system. In this thesis, the evolution of the mast cell chymase locus was analysed by mapping the locus in all available mammalian genome sequences. It was revealed that one single ancestral gene founded this locus probably over 215 million years ago. This ancestor was duplicated more than 185 million years ago. One copy evolved into the α-chymases, whereas the second copy founded the families of ...
At baseline, human chymase gene expression in heart was significantly higher but chymase activity is similar between WT and Tg mice. Treatment with LPS Tg mice showed cardiac hypertrophy, and heart chymase activity tended to show higher than in WT mice but these changes were not statistically significant. Previous studies showed that sepsis is associated with cardiovascular dysfunction [3]. We therefore speculate that LPS-induced cardiovascular dysfunction may be augmented, at least in part, by over-expression of the human chymase gene. This concept is consistent with a recent study by Koga et al. [9] that showed human chymase expression in mice induces mild hypertension with left ventricular hypertrophy, characterized by cardiomyocyte hyperplasia and increased fibrosis in the left ventricle. From this data it is difficult to explain about the role of human chymase in LPS-induced increase mortality is due to cardiovascular dysfunction. Because of the low prevalence of survival of LPS induced Tg ...
In the injured arteries, chymaselike activity and chymase mRNA level were remarkably increased, whereas a slight increase in ACE activity and no increase in ACE mRNA expression were detected. The current study demonstrated for the first time that tranilast prevented vascular chymase expression and effectively inhibited neointima formation and luminal stenosis. Our previous study showed that the vascular ANG II content doubled in the injured arteries compared with that in the uninjured arteries and that an ANG II receptor antagonist but not an ACE inhibitor prevented the neointima formation.15 In the current study, tranilast treatment did not affect plasma ANG II concentration, plasma ACE activity, or PRA. Vascular ANG II-forming activity of chymase increased 4.8-fold in vehicle-treated dogs, whereas tranilast treatment completely prevented the increase in chymase activity. Therefore, the ANG II-forming rate in local vascular tissues supposedly increased after vascular injury but returned to the ...
This work reveals that an active form of human chymase can be captured by α2M, in which form it can cleave small peptide substrates, including angiotensin I, and is protected from irreversible inactivation by serpins and other antipeptidases in biological fluids. We exploited α2M binding to develop a sensitive and specific assay for chymase activity in the serum of subjects with mastocytosis. These studies reveal that chymase, after secretion by mast cells and capture by α2M, can cleave small peptides for longer than once thought possible. Extravascular chymase captured and protected by α2M may be an important source of non-ACE-generated angiotensin II near tissue sites of mast cell degranulation. The portion of α2M-caged chymase making its way to the bloodstream provides the basis of our serum assay and may be a mobile source of angiotensin II-generating chymase in blood and tissues remote from original sites of mast cell degranulation. The half-life of peptidase-bound α2M in blood in ...
The acidic granules of natural killer (NK) cells, T cells, mast cells, and neutrophils store large amounts of serine proteases. Functionally, these proteases are involved, e.g., in the induction of apoptosis, the recruitment of inflammatory cells, and the remodeling of extra-cellular matrix. Among the granule proteases are the phylogenetically related mast cell chymases, neutrophil cathepsin G, and T-cell granzymes (Gzm B to H and Gzm N), which share the characteristic absence of a Cys191-Cys220 bridge. The genes of these proteases are clustered in one locus, the mast cell chymase locus, in all previously investigated mammals. In this paper, we present a detailed analysis of the chymase locus in cattle (Bos taurus) and opossum (Monodelphis domestica). The gained information delineates the evolution of the chymase locus over more than 200 million years. Surprisingly, the cattle chymase locus contains two α-chymase and two cathepsin G genes where all other studied chymase loci have single genes. ...
The most significant findings of this study are that chymase inhibition reduced myocardial infarct size, MMP-9 activation, neutrophil infiltration, MMP-9 containing mast cell accumulation, and inflammatory gene expression after AMI-R. In addition, chymase inhibition was associated with higher levels of total and active eNOS.. Because chymase not only generates Ang II, but also cleaves and activates a variety of physiological substrates including MMPs, procollagen, precursor of interleukin-1β, and stem cell factor, chymase inhibition leads to a variety of effects (Fang et al., 1996, 1997; Kofford et al., 1997; Longley et al., 1997; Patella et al., 1998; Libby, 2002; Tchougounova et al., 2005; Kumar et al., 2009; Pejler et al., 2010). This study demonstrated that chymase inhibition caused myocardial protection after AMI-R through potential multiple mechanisms. A study has demonstrated that MMP-9 knockout mice have increased myocardial protection and attenuated remodeling after experimental AMI ...
In this study, we examined total Ang II-forming activities by analyzing the responsible enzymes in several organs from several species and compared the results with those in humans. Our results suggest that each organ in each species has an unique profile with regard to tissue Ang II formation. The present results suggest that it is difficult to specify an appropriate animal model for studying tissue Ang II formation in humans. None of the organs from any of the species examined had a profile that was identical to those for human tissues. However, chymase-like enzyme predominance in cardiac and aortic Ang II formation was seen not only in human tissue but also in that of most of the other species, except for rabbits and pigs.. In addition, pulmonary chymase-like enzymatic activity was highest in human samples, indicating that chymase-like enzyme in the lung may have a greater physiological role in humans than in other species. Interesting findings in the aorta and heart were that chymase-like ...
Mast cell chymase antibody [CC1] (chymase 1, mast cell) for ELISA, IHC-Fr, IHC-P, WB. Anti-Mast cell chymase mAb (GTX75583) is tested in Human samples. 100% Ab-Assurance.
Mast Cell chymase antibody (chymase 1, mast cell) for IHC-P, WB. Anti-Mast Cell chymase pAb (GTX105829) is tested in Human, Mouse samples. 100% Ab-Assurance.
BACKGROUND: The left ventricular (LV) dilatation of isolated mitral regurgitation (MR) is associated with an increase in chymase and a decrease in interstitial collagen and extracellular matrix. In addition to profibrotic effects, chymase has significant antifibrotic actions because it activates matrix metalloproteinases and kallikrein and degrades fibronectin. Thus, we hypothesize that chymase inhibitor (CI) will attenuate extracellular matrix loss and LV remodeling in MR. METHODS AND RESULTS: We studied dogs with 4 months of untreated MR (MR; n=9) or MR treated with CI (MR+CI; n=8). Cine MRI demonstrated a |40% increase in LV end-diastolic volume in both groups, consistent with a failure of CI to improve a 25% decrease in interstitial collagen in MR. However, LV cardiomyocyte fractional shortening was decreased in MR versus normal dogs (3.71±0.24% versus 4.81±0.31%; P CONCLUSIONS: These results suggest that chymase disrupts cell surface-fibronectin connections and FAK phosphorylation that can
Experimental autoimmune encephalomyelitis (EAE) is a mouse model that reproduces cardinal signs of clinical, histopathological, and immunological features found in Multiple Sclerosis (MS). Mast cells are suggested to be involved in the main inflammatory phases occurring during EAE development, possibly by secreting several autacoids and proteases. Among the latter, the chymase mouse mast cell protease 4 (mMCP-4) can contribute to the inflammatory response by producing endothelin-1 (ET-1). The aim of this study was to determine the impact of mMCP-4 on acute inflammatory stages in EAE. C57BL/6 wild type (WT) or mMCP-4 knockout (KO) mice were immunized with MOG(35-55) plus complete Freunds adjuvant followed by pertussis toxin. Immunized WT mice presented an initial acute phase characterized by progressive increases in clinical score, which were significantly reduced in mMCP-4 KO mice. In addition, higher levels of spinal myelin were found in mMCP-4 KO as compared with WT mice. Finally, whereas EAE ...
Chymases (EC 3.4.21.39) are mast cell serine proteinases that are variably expressed in different species and, in most cases, display either chymotryptic or elastolytic substrate specificity. Given that chymase inhibitors have emerged as potential therapeutic agents for treating various inflammatory, allergic, and cardiovascular disorders, it is important to understand interspecies differences of the enzymes as well as the behavior of inhibitors with them. We have expressed chymases from humans, macaques, dogs, sheep (MCP2 and MCP3), guinea pigs, and hamsters (HAM1 and HAM2) in baculovirus-infected insect cells. The enzymes were purified and characterized with kinetic constants by using chromogenic substrates. We evaluated in vitro the potency of five nonpeptide inhibitors, originally targeted against human chymase. The inhibitors exhibited remarkable cross-species variation of sensitivity, with the greatest potency observed against human and macaque chymases, with K(i) values ranging from ...
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Other names: mast cell protease I; skeletal muscle protease; skin chymotryptic proteinase; mast cell serine proteinase, chymase; skeletal muscle (SK) protease. Comments: In mast cell granules. In peptidase family S1 (trypsin family). Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 97501-92-3. References 1. Woodbury, R.G., Everitt, M. and Neurath, H. Mast cell proteases. Methods Enzymol. 80 (1981) 588-609. [PMID: 7043202]. 2. Powers, J.C., Tanaka, T., Harper, J.W., Minematsu, Y., Barker, L., Lincoln, D., Crumley, K.V., Fraki, J.E., Schechter, N.M., Lazarus, G.G., Nakajima, K., Nakashino, K., Neurath, H. and Woodbury, R.G. Mammalian chymotrypsin-like enzymes. Comparative reactivities of rat mast cell proteases, human and dog skin chymases, and human cathepsin G with peptide 4-nitroanilide substrates and with peptide chloromethyl ketone and sulfonyl fluoride inhibitors. Biochemistry 24 (1985) 2048-2058. [PMID: 3893542]. 3. Johnson, L.A., Moon, K.E. and ...
2015. Background: Previous work has identified mast cells as the major source of chymase largely associated with a profibrotic phenotype. We recently reported increased fibroblast autophagic procollagen degradation in a rat model of pure volume overload (VO). Here we demonstrate a connection between increased fibroblast chymase production and autophagic digestion of procollagen in the pure VO of aortocaval fistula (ACF) in the rat. Methods and results: Isolated LV fibroblasts taken from 4 and 12 week ACF Sprague-Dawley rats have significant increases in chymase mRNA and chymase activity. Increased intracellular chymase protein is documented by immunocytochemistry in the ACF fibroblasts compared to cells obtained from age-matched sham rats. To implicate VO as a stimulus for chymase production, we show that isolated adult rat LV fibroblasts subjected to 24 h of 20% cyclical stretch induces chymase mRNA and protein production. Exogenous chymase treatment of control isolated adult cardiac ...
During the first 30 years at Tokushima University, Professor Katunumas main research was about the enzymes involved in vitamin B6 metabolism and their intracellular protein turnover. Together with his colleague Mitsuko Okada, he discovered mitochondrial glutamicoxalacetic transaminase and the urea cycle glutaminase isoenzymes. Later on, with his colleague Yasuhiro Kuroda, he established the enzymes functions in the hepatocarcinogenesis. In 1971, he discovered the acceleration of pyridoxal enzyme turnover in animals with vitamin B6 deficiency and the enzymes participate in proteolysis of the apoproteins. These discoveries suggested that protein degradation can be initiated by the apoprotein formation in proteolysis process. This idea provoke further research into the initiation of various biochemical pathways by limited proteolysis, such as prothrombin activation by mast cell tryptase histamine release by mast cell chymase, and initiation of influenza virus entry by tryptase Clara. In his later ...
Semantic Scholar extracted view of [The enhanced activity of chymotrypsin-like proteinases in the blood plasma of patients with hereditary hypercholesterolemia and the means for its correction]. by O. G. Ogloblina et al.
1PJP: The 2.2 A crystal structure of human chymase in complex with succinyl-Ala-Ala-Pro-Phe-chloromethylketone: structural explanation for its dipeptidyl carboxypeptidase specificity.
Endothelin is the most potent constrictor of human blood vessels known to man. In mammals, there are three structurally and pharmacologically separate ET isopeptides: ET-1, ET-2, and ET-3 (Volpe 46). Endothelin-1 is the primary isoform in the human cardiovascular system and is a 21-amino acid peptide produced chiefly by endothelial cells (Lüscher 2434). Endothelin-converting enzymes (ECE), chymases, and non-ECE metalloproteases are responsible for the synthesis of ET-1 by means of autocrine regulation (Lüscher 2434). ET-1 operates through the initiation of two G-protein coupled receptors: ETA and ETB. Located on vascular smooth muscle cells, ETA receptors regulate vasoconstriction and cell proliferation. ETB receptors, situated on endothelial cells, mediate endothelium-dependent vasodilation through the release of nitric oxide and prostacyclin (Haapaniemi 721). In addition to its cardiovascular and mitogenic effects, endothelin-1 is involved in gastrointestinal and endocrine function, ...
Treatment options are limited for severe asthma, and the need for additional therapies remains great. Previously, we demonstrated that integrin αvβ6-deficient mice are protected from airway hyperresponsiveness, due in part to increased expression of the murine ortholog of human chymase. Here, we determined that chymase protects against cytokine-enhanced bronchoconstriction by cleaving fibronectin to impair tension transmission in airway smooth muscle (ASM). Additionally, we identified a pathway that can be therapeutically targeted to mitigate the effects of airway hyperresponsiveness. Administration of chymase to human bronchial rings abrogated IL-13-enhanced contraction, and this effect was not due to alterations in calcium homeostasis or myosin light chain phosphorylation. Rather, chymase cleaved fibronectin, inhibited ASM adhesion, and attenuated focal adhesion phosphorylation. Disruption of integrin ligation with an RGD-containing peptide abrogated IL-13-enhanced contraction, with no ...
Treatment options are limited for severe asthma, and the need for additional therapies remains great. Previously, we demonstrated that integrin αvβ6-deficient mice are protected from airway hyperresponsiveness, due in part to increased expression of the murine ortholog of human chymase. Here, we determined that chymase protects against cytokine-enhanced bronchoconstriction by cleaving fibronectin to impair tension transmission in airway smooth muscle (ASM). Additionally, we identified a pathway that can be therapeutically targeted to mitigate the effects of airway hyperresponsiveness. Administration of chymase to human bronchial rings abrogated IL-13-enhanced contraction, and this effect was not due to alterations in calcium homeostasis or myosin light chain phosphorylation. Rather, chymase cleaved fibronectin, inhibited ASM adhesion, and attenuated focal adhesion phosphorylation. Disruption of integrin ligation with an RGD-containing peptide abrogated IL-13-enhanced contraction, with no ...
Treatment options are limited for severe asthma, and the need for additional therapies remains great. Previously, we demonstrated that integrin αvβ6-deficient mice are protected from airway hyperresponsiveness, due in part to increased expression of the murine ortholog of human chymase. Here, we determined that chymase protects against cytokine-enhanced bronchoconstriction by cleaving fibronectin to impair tension transmission in airway smooth muscle (ASM). Additionally, we identified a pathway that can be therapeutically targeted to mitigate the effects of airway hyperresponsiveness. Administration of chymase to human bronchial rings abrogated IL-13-enhanced contraction, and this effect was not due to alterations in calcium homeostasis or myosin light chain phosphorylation. Rather, chymase cleaved fibronectin, inhibited ASM adhesion, and attenuated focal adhesion phosphorylation. Disruption of integrin ligation with an RGD-containing peptide abrogated IL-13-enhanced contraction, with no ...
Treatment options are limited for severe asthma, and the need for additional therapies remains great. Previously, we demonstrated that integrin αvβ6-deficient mice are protected from airway hyperresponsiveness, due in part to increased expression of the murine ortholog of human chymase. Here, we determined that chymase protects against cytokine-enhanced bronchoconstriction by cleaving fibronectin to impair tension transmission in airway smooth muscle (ASM). Additionally, we identified a pathway that can be therapeutically targeted to mitigate the effects of airway hyperresponsiveness. Administration of chymase to human bronchial rings abrogated IL-13-enhanced contraction, and this effect was not due to alterations in calcium homeostasis or myosin light chain phosphorylation. Rather, chymase cleaved fibronectin, inhibited ASM adhesion, and attenuated focal adhesion phosphorylation. Disruption of integrin ligation with an RGD-containing peptide abrogated IL-13-enhanced contraction, with no ...
Treatment options are limited for severe asthma, and the need for additional therapies remains great. Previously, we demonstrated that integrin αvβ6-deficient mice are protected from airway hyperresponsiveness, due in part to increased expression of the murine ortholog of human chymase. Here, we determined that chymase protects against cytokine-enhanced bronchoconstriction by cleaving fibronectin to impair tension transmission in airway smooth muscle (ASM). Additionally, we identified a pathway that can be therapeutically targeted to mitigate the effects of airway hyperresponsiveness. Administration of chymase to human bronchial rings abrogated IL-13-enhanced contraction, and this effect was not due to alterations in calcium homeostasis or myosin light chain phosphorylation. Rather, chymase cleaved fibronectin, inhibited ASM adhesion, and attenuated focal adhesion phosphorylation. Disruption of integrin ligation with an RGD-containing peptide abrogated IL-13-enhanced contraction, with no ...
Treatment options are limited for severe asthma, and the need for additional therapies remains great. Previously, we demonstrated that integrin αvβ6-deficient mice are protected from airway hyperresponsiveness, due in part to increased expression of the murine ortholog of human chymase. Here, we determined that chymase protects against cytokine-enhanced bronchoconstriction by cleaving fibronectin to impair tension transmission in airway smooth muscle (ASM). Additionally, we identified a pathway that can be therapeutically targeted to mitigate the effects of airway hyperresponsiveness. Administration of chymase to human bronchial rings abrogated IL-13-enhanced contraction, and this effect was not due to alterations in calcium homeostasis or myosin light chain phosphorylation. Rather, chymase cleaved fibronectin, inhibited ASM adhesion, and attenuated focal adhesion phosphorylation. Disruption of integrin ligation with an RGD-containing peptide abrogated IL-13-enhanced contraction, with no ...
Treatment options are limited for severe asthma, and the need for additional therapies remains great. Previously, we demonstrated that integrin αvβ6-deficient mice are protected from airway hyperresponsiveness, due in part to increased expression of the murine ortholog of human chymase. Here, we determined that chymase protects against cytokine-enhanced bronchoconstriction by cleaving fibronectin to impair tension transmission in airway smooth muscle (ASM). Additionally, we identified a pathway that can be therapeutically targeted to mitigate the effects of airway hyperresponsiveness. Administration of chymase to human bronchial rings abrogated IL-13-enhanced contraction, and this effect was not due to alterations in calcium homeostasis or myosin light chain phosphorylation. Rather, chymase cleaved fibronectin, inhibited ASM adhesion, and attenuated focal adhesion phosphorylation. Disruption of integrin ligation with an RGD-containing peptide abrogated IL-13-enhanced contraction, with no ...
Treatment options are limited for severe asthma, and the need for additional therapies remains great. Previously, we demonstrated that integrin αvβ6-deficient mice are protected from airway hyperresponsiveness, due in part to increased expression of the murine ortholog of human chymase. Here, we determined that chymase protects against cytokine-enhanced bronchoconstriction by cleaving fibronectin to impair tension transmission in airway smooth muscle (ASM). Additionally, we identified a pathway that can be therapeutically targeted to mitigate the effects of airway hyperresponsiveness. Administration of chymase to human bronchial rings abrogated IL-13-enhanced contraction, and this effect was not due to alterations in calcium homeostasis or myosin light chain phosphorylation. Rather, chymase cleaved fibronectin, inhibited ASM adhesion, and attenuated focal adhesion phosphorylation. Disruption of integrin ligation with an RGD-containing peptide abrogated IL-13-enhanced contraction, with no ...
Treatment options are limited for severe asthma, and the need for additional therapies remains great. Previously, we demonstrated that integrin αvβ6-deficient mice are protected from airway hyperresponsiveness, due in part to increased expression of the murine ortholog of human chymase. Here, we determined that chymase protects against cytokine-enhanced bronchoconstriction by cleaving fibronectin to impair tension transmission in airway smooth muscle (ASM). Additionally, we identified a pathway that can be therapeutically targeted to mitigate the effects of airway hyperresponsiveness. Administration of chymase to human bronchial rings abrogated IL-13-enhanced contraction, and this effect was not due to alterations in calcium homeostasis or myosin light chain phosphorylation. Rather, chymase cleaved fibronectin, inhibited ASM adhesion, and attenuated focal adhesion phosphorylation. Disruption of integrin ligation with an RGD-containing peptide abrogated IL-13-enhanced contraction, with no ...
Treatment options are limited for severe asthma, and the need for additional therapies remains great. Previously, we demonstrated that integrin αvβ6-deficient mice are protected from airway hyperresponsiveness, due in part to increased expression of the murine ortholog of human chymase. Here, we determined that chymase protects against cytokine-enhanced bronchoconstriction by cleaving fibronectin to impair tension transmission in airway smooth muscle (ASM). Additionally, we identified a pathway that can be therapeutically targeted to mitigate the effects of airway hyperresponsiveness. Administration of chymase to human bronchial rings abrogated IL-13-enhanced contraction, and this effect was not due to alterations in calcium homeostasis or myosin light chain phosphorylation. Rather, chymase cleaved fibronectin, inhibited ASM adhesion, and attenuated focal adhesion phosphorylation. Disruption of integrin ligation with an RGD-containing peptide abrogated IL-13-enhanced contraction, with no ...
Regulation of skeletal muscle development and organization is a complex process that is not fully understood. Here, we focused on amphiphysin 2 (BIN1, also known as bridging integrator-1) and dynamin 2 (DNM2), two ubiquitous proteins implicated in membrane remodeling and mutated in centronuclear myopathies (CNMs). We generated Bin1-/- Dnm2+/- mice to decipher the physiological interplay between BIN1 and DNM2. While Bin1-/- mice die perinatally from a skeletal muscle defect, Bin1-/- Dnm2+/- mice survived at least 18 months, and had normal muscle force and intracellular organization of muscle fibers, supporting BIN1 as a negative regulator of DNM2. We next characterized muscle-specific isoforms of BIN1 and DNM2. While BIN1 colocalized with and partially inhibited DNM2 activity during muscle maturation, BIN1 had no effect on the isoform of DNM2 found in adult muscle. Together, these results indicate that BIN1 and DNM2 regulate muscle development and organization, function through a common pathway, ...
In this study the diversity of mast cell proteases and some of the factors regulating mast cell growth and protease expression were examined in rodents. Five proteases were isolated from mouse small intestinal mucosa and their substrate specificities defined. The isolated proteases were all of mast cell origin and were chymotrypsin-like in their substrate specificities. The proteases were all identified as variants of mouse mast cell protease-1 which differed only in their carbohydrate moieties. Despite the fact that these enzymes shared a common core polypeptide they all differed significantly in the rate at which they hydrolysed synthetic substrates and in the rates at which they were inhibited by α1-proteinase inhibitor. A related, but distinct protease was isolated from peritoneal cavity mast cells of mice. This enzyme, also a chymase, had N-terminal sequence identity with mouse mast cell protease-4. This enzyme was not inhibited by α1-proteinase inhibitor. Factors which regulate mast cell ...
The acidic granules of natural killer (NK) cells, T cells, mast cells, and neutrophils store large amounts of serine proteases. Functionally, these proteases are involved, e.g., in the induction of apoptosis, the recruitment of inflammatory cells, and the remodeling of extra-cellular matrix. Among the granule proteases are the phylogenetically related mast cell chymases, neutrophil cathepsin G, and T-cell granzymes (Gzm B to H and Gzm N), which share the characteristic absence of a Cys191-Cys220 bridge. The genes of these proteases are clustered in one locus, the mast cell chymase locus, in all previously investigated mammals. In this paper, we present a detailed analysis of the chymase locus in cattle (Bos taurus) and opossum (Monodelphis domestica). The gained information delineates the evolution of the chymase locus over more than 200 million years. Surprisingly, the cattle chymase locus contains two α-chymase and two cathepsin G genes where all other studied chymase loci have single genes. ...
Tryptase (EC 3.4.21.59, ) is the most abundant secretory granule-derived serine proteinase contained in mast cells and has been used as a marker for mast cell activation. Club cells contain tryptase which is believed to be responsible for cleaving the hemagglutinin surface protein of influenza A virus, thereby activating it and causing the symptoms of flu. Tryptase is also known by mast cell tryptase, mast cell protease II, skin tryptase, lung tryptase, pituitary tryptase, mast cell neutral proteinase, mast cell serine proteinase II, mast cell proteinase II, mast cell serine proteinase tryptase, rat mast cell protease II, and tryptase M. Serum levels are normally less than 11.5 ng/mL. Elevated levels of serum tryptase occur in both anaphylactic and anaphylactoid reactions, but a negative test does not exclude anaphylaxis. Tryptase is less likely to be elevated in food allergy reactions as opposed to other causes of anaphylaxis. Serum typtase levels are also elevated in and used as one indication ...
The ATP-binding cassette transporter A1 (ABCA1) mediates the efflux of cellular unesterified cholesterol and phospholipid to lipid-poor apolipoprotein A-I. Chymase, a protease secreted by mast cells, selectively cleaves pre-β-migrating particles from high density lipoprotein (HDL)3 and reduces the efflux of cholesterol from macrophages. To evaluate whether this effect is the result of reduction of ABCA1-dependent or -independent pathways of cholesterol efflux, in this study we examined the efflux of cholesterol to preparations of chymase-treated HDL3 in two types of cell: 1) in J774 murine macrophages endogenously expressing low levels of scavenger receptor class B, type I (SR-BI), and high levels of ABCA1 upon treatment with cAMP; and 2) in Fu5AH rat hepatoma cells endogenously expressing high levels of the SR-BI and low levels of ABCA1. Treatment of HDL3 with the human chymase resulted in rapid depletion of pre-β-HDL and a concomitant decrease in the efflux of cholesterol and phospholipid ...
Peptides , Angiotensins and Related Peptides , Angiotensin II, human; The octapeptide angiotensin II (Ang II) exerts a wide range of effects on the cardiovascular system. It is also implicated in the regulation of cell proliferation, fibrosis and apoptosis. Ang II is formed by cleavage of Ang I by the angiotensin-converting enzyme (ACE) or chymases. Human heart chymase, a chymotrypsin-like serine proteinase, hydrolyzes the Phe8-His9 bond to yield the octapeptide hormone angiotensin II and His-Leu.; DRVYIHPF; H-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-OH
Expression of Mast Cell Proteases Correlates with Mast Cell Maturation and Angiogenesis during Tumor Progression. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
1NC6: Potent, Small-Molecule Inhibitors of Human Mast Cell Tryptase. Antiasthmatic Action of a Dipeptide-Based Transition-State Analogue Containing a Benzothiazole Ketone.
Given that 80% of angiotensin II-forming activity in kidney, coronary heart and blood vessels is dependent on chymase, a single may suppose that chymase
Background: We hypothesized that food allergy causes a state of non-specific jejunal dysmotility. This was tested in a mouse model. Methods: Balb/c mice were epicutaneously sensitized with ovalbumin and challenged with 10 intragastric ovalbumin administrations every second day. Smooth muscle contractility of isolated circular jejunal sections was studied in organ bath with increasing concentrations of carbamylcholine chloride (carbachol). Smooth muscle layer thickness and mast cell protease-1 (MMCP-1) positive cell density were assayed histologically. Serum MMCP-1 and immunoglobulins were quantified by ELISA, and mRNA expressions of IFN-γ, IL-4, IL-6 and TGFβ-1 from jejunal and ileal tissue segments were analyzed with quantitative real-time PCR. Results: Ovalbumin-specific serum IgE correlated with jejunal MMCP-1+ cell density. In the allergic mice, higher concentrations of carbachol were required to reach submaximal muscular stimulation, particularly in preparations derived from mice with ...
A study from Emory University School of Medicine hints that dying cardiac muscle cells could be saved, past the time when this is usually thought possible.
マウス・モノクローナル抗体 ab2378 交差種: Ms,Rat,Hu 適用: WB,ELISA,IHC-P,ICC,IHC-R,ICC/IF…Mast Cell Tryptase抗体一覧…画像、プロトコール、文献などWeb上の情報が満載のアブカムの…
YFP and Cre are expressed from the basophil-specific |i|Mcpt8|/i| (mast cell protease 8; also known as Basoph8) promoter in this targeted mutation strain. This strain is useful for labeling, sorting and deleting basophil cell populations.
천식의 기도염증 측면에서 경증-중등증 천식과 다른 중증 천식만의 고유한 특징에 대해서는 명확히 알려져 있지 않다. 천식의 병태생리적 특징에 대한 연구를 수행하고 있는 SARP에서는 기관지내시경을 통하여 기관지생검과 기관지폐포세척을 통한 샘플을 수집하고 있으며, 중증 천식에서도 기관지 내시경이 안전하게 시행될 수 있음을 보여주었다[23]. 염증세포 중에서 비반세포는 IgE 매개반응을 통하여 히스타민을 분비하는 등 염증과정에 관여하는데, 중증 천식환자의 기도에서 chymase 양성 비반세포의 침윤이 높은 것으로 나타났고, 특히 상피세포내에 높게 존재하였다[24]. 또한 객담 염증세포 분석을 통해서 염증세포의 특성을 살펴보았을 때 호산구와 함께 중성구가 높은 그룹에서 폐기능의 저하와 낮은 천식조절 상태를 보였다[25]. 이러한 결과들은 중증 ...
network provider has been approved by a MMCP to deliver specific.. SSI - CDC. Jan 1, 2019 … January 2019. 9-1 … Review of medical records or surgery clinic patient ...
T cell mediated immune responses in the gut can produce enteropathy and malabsorption. We have investigated the relevance of mucosal mast cells (MMC) to the mechanisms of this enteropathy by using graft-versus-host reaction (GvHR) in the rat as a model of mucosal delayed type hypersensitivity. Measurements of mucosal architecture, intraepithelial lymphocytes (IEL) and MMC counts were performed in control and experimental rats, and release of rat mast cell protease II (RMCPII) into the bloodstream was used as an index of MMC activation. In unirradiated rats, jejunal MMC count was increased on day 14 of the GvHR (mean 272/mm2 v 182 in controls, p less than 0.01), as was serum RMCPII (p less than 0.01). Irradiated rats (4.5 Gy, reconstituted with isogeneic spleen cells) had low counts of IEL and crypt hyperplasia seven to 14 days after irradiation. Irradiated rats with GvHR (induced by ip injection of parental strain spleen cells) and studied on days 7, 10 and 14, had significant enteropathy with ...
TY - JOUR. T1 - Ultrastructural immunolocalization of basic fibroblast growth factor in mast cell secretory granules. T2 - Morphological evidence for bFGF release through degranulation. AU - Qu, Zhenhong. AU - Kayton, Robert J.. AU - Ahmadi, Proochista. AU - Liebler, Janice M.. AU - Powers, Michael R.. AU - Planck, Stephen R.. AU - Rosenbaum, James T.. PY - 1998/10. Y1 - 1998/10. N2 - We previously reported that mast cells (MCs) serve as a source of basic fibroblast growth factor (bFGF), a potent angiogenic and mitogenic polypeptide, suggesting that bFGF may mediate MC-related neovascularization and fibroproliferation. Unlike many other growth factors, bFGF lacks a classic peptide sequence for its secretion, and the mechanism(s) for its release remains controversial. Because MCs release a wide spectrum of bioactive products via degranulation, we hypothesized that MC degranulation may be a mechanism of bFGF release and used ultrastructural immunohistochemistry to test the hypothesis. We reasoned ...
Tryptases, the dominant secretory granular proteins from human mast cells, are emerging as important mediators in asthma and allergy. The β- and α- tryptases have highly similar nucleotide sequences and located on the same locus. While the entire population expresses β-tryptase, the α-tryptase gene exhibits copy number variation (CNV). We have studied the association of expression of these allelic variants with asthma or allergic diseases. We have investigated also the potential actions of β- and α-tryptases in vitro and in vivo. We have found that the one alpha tryptase copy allele was significantly associated with lower total serum IgE levels (Z= -2.39, p=0.01) and a tri-allelic architecture with alleles carrying no, one or two copies of the α-tryptase gene was postulated. The addition of βtryptase to epithelial cells induced upregulation of mRNA for IL-8, IL-6 and TNF-α, while α-tryptase on the other hand was without effect in this model. Injection of β-tryptase into the mouse ...
European network for development of electroporation-based technologies and treatments. This COST Action aims at fostering development of new and existing electroporation-based applications and as well as facilitating coordination and interdisciplinary exchange of knowledge and know-how between researchers from different scientific fields and countries. Action results will provide scientific and technological progress in the field of medicine, biotechnology and environment preservation.
TY - JOUR. T1 - Involvement of p38 MAP kinase and Smad3 in TGF-β-mediated mast cell functions. AU - Funaba, Masayuki. AU - Ikeda, Teruo. AU - Murakami, Masaru. AU - Ogawa, Kenji. AU - Nishino, Yoshii. AU - Tsuchida, Kunihiro. AU - Sugino, Hiromu. AU - Abe, Matanobu. PY - 2006/12/1. Y1 - 2006/12/1. N2 - Transforming growth factor-β (TGF-β) modulates functions of bone marrow-derived cultured mast cells (BMMCs); cell maturation (up-regulation of mouse mast cell proteases (mmcps)), growth arrest and migration. We investigated the roles of p38 MAP kinase and Smad3 in TGF-β-mediated cell responses in BMMCs. Treating BMMCs with TGF-β induced the phosphorylation of p38 within 2 h and persisted for 24 h. The involvement of p38 in TGF-β-induced cell responses depended upon mast cell functions; it was necessary for up-regulation of mmcp-1 and migration, but not for up-regulation of mmcp-7 and inhibition of metabolic activity. New protein synthesis was required for the up-regulation of mmcp-1 but not ...
Shop Leech-derived tryptase inhibitor ELISA Kit, Recombinant Protein and Leech-derived tryptase inhibitor Antibody at MyBioSource. Custom ELISA Kit, Recombinant Protein and Antibody are available.
phdthesis{d683936c-1726-4ede-86a7-193f0162cd84, abstract = {Mast cell are found throughout the body, but are especially prominent in tissues that have direct contact with the external milieu such as the skin, gastrointestinal tract and lungs. Mast cells are commonly recognized for their detrimental role in allergic reactions and can, upon activation through the high-affinity receptor for IgE (FcεRI), rapidly produce and secrete many of the mediators responsible for the typical symptoms in urticaria, asthma and rhinitis. However, increasing amount of data show that mast cells have important, even vital, roles in host defence against bacteria, viruses, parasites and venoms. Mast cells exist as two different subtypes, MCT (mucosal mast cells) and MCTC (connective tissue mast cells). These two subtypes differ in their molecular expression and distribution in the body. MCT are for example the dominating subtype in the lungs, while MCTC are most common in the skin and the gastrointestinal tract. ...
Tryptase is a member of the serine protease S1 family. It is the predominant neutral protease of the mast cell granules. Within the mast cell granule it exists as a hepar
Peptides , Angiotensins and Related Peptides , ClearPoint Angiotensin I, human, 13C and 15N labeled; This peptide is angiontensin I (Ang I) with valine and isoleucine universally labeled with 13C and N. Ang I is a precursor to Ang II, which has been implicated in cardiovascular functions, cell proliferation, fibrosis, and apoptosis. The 10-mer Ang I peptide is converted to Ang II through the cleavage of the Phe8-His9 bond of Ang I by angiotensin-converting enzyme (ACE) or human chymase.; DR-V*-Y-I*-HPFHL [Val* = Val(U-13C5,15N); Ile* = Ile(U-13C6,15N)]; H-Asp-Arg-Val*-Tyr-Ile*-His-Pro-Phe-His-Leu-OH [Val* = Val(U-13C5,15N); Ile* = Ile(U-13C6,15N)]
Analytical Enzyme Tryptase products offered by Sigma-Aldrich online. Tryptase is a tetrameric glycoprotein and a member of the serine protease S1 family. It is the predominant neutral protease of the mast cell granules.
Major secreted protease of mast cells with suspected roles in vasoactive peptide generation, extracellular matrix degradation, and regulation of gland secretion.
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... and heterogeneity of mast cells with particular regard to the mast cell-specific proteases chymase and tryptase". Journal of ...
... including the serine protease chymase. The activity of local renin-angiotensin systems and alternative pathways of angiotensin ...
... chymase, vasoactive intestinal peptide (VIP), vascular endothelial growth factor (VEGF), TNF, prostaglandins, leukotrienes, and ...
... a is the activated form of the coagulation factor thrombokinase, known eponymously as Stuart-Prower factor. Factor X is an enzyme, a serine endopeptidase, which plays a key role at several stages of the coagulation system. Factor X is synthesized in the liver. The most commonly used anticoagulants in clinical practice, warfarin and the heparin series of anticoagulants and fondaparinux, act to inhibit the action of Factor Xa in various degrees. Traditional models of coagulation developed in the 1960s envisaged two separate cascades, the extrinsic (tissue factor (TF)) pathway and the intrinsic pathway. These pathways converge to a common point, the formation of the Factor Xa/Va complex which together with calcium and bound on a phospholipids surface generate thrombin (Factor IIa) from prothrombin (Factor II). A new model, the cell-based model of anticoagulation appears to explain more fully the steps in coagulation. This model has three stages: 1) initiation of coagulation on TF-bearing ...
Luo C, Thielens NM, Gagnon J, Gal P, Sarvari M, Tseng Y, Tosi M, Zavodszky P, Arlaud GJ, Schumaker VN (May 1992). "Recombinant human complement subcomponent C1s lacking beta-hydroxyasparagine, sialic acid, and one of its two carbohydrate chains still reassembles with C1q and C1r to form a functional C1 complex". Biochemistry. 31 (17): 4254-62. doi:10.1021/bi00132a015. PMID 1533159 ...
Protein HtrA2, also known as Omi, is a mitochondrially-located serine protease. The human protein Serine protease HTRA2, mitochondrial is 49kDa in size and composed of 458 amino acids. The peptide fragment of 1-31 amino acid is the mitochondrial transition sequence, fragment 32-133 amino acid is propertied, and 134-458 is the mature protein Serine protease HTRA2, mitochondrial, and its theoretical pI of this protein is 6.12.[10] HtrA2 shows similarities with DegS, a bacterial protease present in the periplasm of gram-negative bacteria. Structurally, HtrA2 is a trimeric molecule with central protease domains and a carboxy-terminal PDZ domain, which is characteristic of the HtrA family. The PDZ domain preferentially binds C-terminus of the protein substrate and modulate the proteolytic activity of the trypsin-like protease domain.[11] ...
Seol JH, Woo SK, Jung EM, Yoo SJ, Lee CS, Kim KJ, Tanaka K, Ichihara A, Ha DB, Chung CH (April 1991). "Protease Do is essential for survival of Escherichia coli at high temperatures: its identity with the htrA gene product". Biochemical and Biophysical Research Communications. 176 (2): 730-6. doi:10.1016/s0006-291x(05)80245-1. PMID 2025286 ...
Text is available under the Creative Commons Attribution-ShareAlike License; additional terms may apply. By using this site, you agree to the Terms of Use and Privacy Policy. Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc., a non-profit organization ...
A trypsin inhibitor (TI) is a protein and a type of serine protease inhibitor (serpin) that reduces the biological activity of trypsin by controlling the activation and catalytic reactions of proteins.[1] Trypsin is an enzyme involved in the breakdown of many different proteins, primarily as part of digestion in humans and other animals such as monogastrics and young ruminants. When trypsin inhibitor is consumed it acts as an irreversible and competitive substrate.[2] It competes with proteins to bind to trypsin and therefore renders it unavailable to bind with proteins for the digestion process.[1] As a result, protease inhibitors that interfere with digestion activity have an antinutritional effect. Therefore, trypsin inhibitor is considered an anti-nutritional factor or ANF.[3] Additionally, trypsin inhibitor partially interferes with chymotrypsin function. Trypsinogen is an inactive form of trypsin, its inactive form ensures protein aspects of the body, such as the pancreas and muscles, are ...
Cholecystokinin (CCK) is a unique peptide released by the duodenal "I cells" in response to chyme containing high fat or protein content. Unlike secretin, which is an endocrine hormone, CCK actually works via stimulation of a neuronal circuit, the end-result of which is stimulation of the acinar cells to release their content.[5] CCK also increases gallbladder contraction, causing release of pre-stored bile into the cystic duct, and eventually into the common bile duct and via the ampulla of Vater into the second anatomic position of the duodenum. CCK also decreases the tone of the sphincter of Oddi, which is the sphincter that regulates flow through the ampulla of Vater. CCK also decreases gastric activity and decreases gastric emptying, thereby giving more time to the pancreatic juices to neutralize the acidity of the gastric chyme ...
... chymase or other enzymes can transform it into angiotensin II.[11][12][13] This process can be intracellular or interstitial.[7 ...
... Kazi Rafiq1 , Yu-Yan Fan1, Shamshad J. ... Chymase activity in the heart and skin was evaluated in mice treated with LPS (0.03 or 0.1 mg). Heart chymase activity was not ... At baseline, human chymase gene expression in heart was significantly higher but chymase activity is similar between WT and Tg ... Keywords: human chymase transgenic mice, chymase activity and lipopolysaccharide, endotoxemia Introduction. Sepsis is a common ...
ACE and Chymase mRNA Levels of Carotid Arteries. The chymase mRNA level of vehicle-treated injured arteries exhibited an ... Because chymase is synthesized mainly in mast cells, we assumed that the chymase-dependent ANG II formation could be ... The direct inhibitory effect of tranilast on the catalytic activity of chymase was analyzed with purified human chymase (from ... 20 The PCR primers for dog chymase were selected according to the dog chymase cDNA sequence22 (sense primer: 5′- ...
... chymase 1, mast cell) for ELISA, IHC-Fr, IHC-P, WB. Anti-Mast cell chymase mAb (GTX75583) is tested in Human samples. 100% Ab- ... chymase 1, mast cell. Background. This gene encodes a chymotryptic serine proteinase that belongs to the peptidase family S1. ... Specifications: Mast cell chymase antibody [CC1]. Full Name. ... Mast cell chymase antibody [CC1] See all Mast cell chymase ...
... low-dose chymase (n = 4), high-dose chymase (n = 4), or high-dose chymase plus chymase inhibitor (n = 4). Infarct size (V, 41 ... low-dose human purified chymase (10 ng/ml), high-dose chymase (30 ng/ml), or high-dose chymase plus chymase inhibitor (10 μM). ... Purified human chymase induced fibroblast proliferation, which was blocked by chymase inhibition. Indeed, chymase inhibition ... Chymase Activity.. Chymase activity (mU/mg protein) in both AAR (V, 9.7 ± 2.6; CM, 1.1 ± 0.3; P = 0.01) and NLV (V, 18.7 ± 6.1 ...
Surprisingly, the cattle chymase locus contains two α-chymase and two cathepsin G genes where all other studied chymase loci ... Phylogenetic analyses place one of the opossum genes firmly with mast cell α-chymases, which indicates that the α-chymase had ... These proteases belong to the chymase or the tryptase family, which are encoded from the mast cell chymase and the multigene ... Graspases are encoded from the mast cell chymase locus. The human locus holds four genes: α-chymase, cathepsin G, and granzymes ...
Graspases are encoded from the mast cell chymase locus. The human locus holds four genes: α-chymase, cathepsin G, and granzymes ... These two chymases may have coevolved with an in vivo substrate that is conserved only in the positions with a common ... Human chymase (HC) constitutes a major granule protease in one of the two human mast cell (MC) types. The main biological role ... 1. Sculpted through Time: Evolution and Function of Serine Proteases from the Mast Cell Chymase Locus. Open this publication in ...
Exogenous chymase treatment of control isolated adult cardiac fibroblasts demonstrates that chymase is internalized through a ... Chymase inhibitor treatment reduces cyclical stretch-induced autophagy in isolated cardiac fibroblasts, demonstrating chymases ... Isolated LV fibroblasts taken from 4 and 12 week ACF Sprague-Dawley rats have significant increases in chymase mRNA and chymase ... Increased fibroblast chymase production mediates procollagen autophagic digestion in volume overload Academic Article ...
Thus, we hypothesize that chymase inhibitor (CI) will attenuate extracellular matrix loss and LV remodeling in MR. METHODS AND ... In addition to profibrotic effects, chymase has significant antifibrotic actions because it activates matrix metalloproteinases ... is associated with an increase in chymase and a decrease in interstitial collagen and extracellular matrix. ... These results suggest that chymase disrupts cell surface-fibronectin connections and FAK phosphorylation that can adversely ...
Categories: Chymase , Human , Large Structures , Abad, M C , Bayoumy, S , Crysler, C , Deckman, I , Degaravilla, L , Greco, M N ... Chymases (EC 3.4.21.39) are mast cell serine proteinases that are variably expressed in different species and, in most cases, ... We have expressed chymases from humans, macaques, dogs, sheep (MCP2 and MCP3), guinea pigs, and hamsters (HAM1 and HAM2) in ... Given that chymase inhibitors have emerged as potential therapeutic agents for treating various inflammatory, allergic, and ...
... such as prothrombin activation by mast cell tryptase histamine release by mast cell chymase, and initiation of influenza virus ...
The side chains of residues Phe191 and Lys192 of pro-chymase fill the Ile16 binding pocket and the base of the S1 binding ... Human chymase is a protease involved in physiological processes ranging from inflammation to hypertension. As are all proteases ... Human chymase is a protease involved in physiological processes ranging from inflammation to hypertension. As are all proteases ... The 1.8 A structure of pro-chymase, reported here, is the first zymogen with a dipeptide pro region (glycine-glutamate) to be ...
sp,P21844,CMA1_MOUSE Chymase OS=Mus musculus GN=Cma1 PE=1 SV=2 MHLLTLHLLLLLLGSSTKAGEIIGGTECIPHSRPYMAYLEIVTSENYLSACSGFLIRRNF ...
Chymase (EC:3.4.21.39*Search proteins in UniProtKB for this EC number. ... "Identification of a highly specific chymase as the major angiotensin II-forming enzyme in the human heart.". Urata H., ... "Structure, chromosomal assignment, and deduced amino acid sequence of a human gene for mast cell chymase.". Caughey G.H., ... "Functional evidence for a role of vascular chymase in the production of angiotensin II in isolated human arteries.". Richard V. ...
Mouse monoclonal Mast Cell Chymase antibody [CC1]. Validated in IHC and tested in Human. Cited in 26 publication(s). ... All lanes : Anti-Mast Cell Chymase antibody [CC1] (ab2377) at 1 µg/ml. Lane 1 : Recombinant Human Chymase Protein. Lane 2 : ... Anti-Mast Cell Chymase antibody [CC1]. See all Mast Cell Chymase primary antibodies. ... mast cell chymase. Would it be possible to have the immunogen sequence so that I can assess whether this would be suitable for ...
GAPDH-normalized chymase 1, chymase 2, chymase 4, and chymase 5 mRNA levels in aortae from vehicle- or captopril-treated MC+/+ ... Involvement of chymase-mediated angiotensin II generation in blood pressure regulation.. Li M1, Liu K, Michalicek J, Angus JA, ... Chymase, a human mast cell protease, has recently been proposed to play a role in blood pressure regulation because of its Ang ... Involvement of chymase-mediated angiotensin II generation in blood pressure regulation. J Clin Invest. 2004 Jul 1;114(1):112- ...
Relationship of small airway chymase-positive mast cells and lung function in severe asthma.. Balzar S1, Chu HW, Strand M, ... Chymase-positive mast cells: a double-edged sword in asthma? [Am J Respir Crit Care Med. 2005] ... In contrast, mast cell number, percentage, and the chymase-positive phenotype increased in small airway regions. After the ... tryptase and chymase). Specific cell distributions were determined and correlated with lung function measures. The number of ...
Invitrogen Anti-Mast Cell Chymase Monoclonal (CC1), Catalog # MA5-11717. Tested in Western Blot (WB) and Immunohistochemistry ( ... Protein Aliases: Alpha-chymase; Chymase; chymase 1 preproprotein transcript E; chymase 1 preproprotein transcript I; chymase 1 ... Cite Mast Cell Chymase Monoclonal Antibody (CC1). The following antibody was used in this experiment: Mast Cell Chymase ... mast cell; chymase, heart; chymase, mast cell; mast cell; Mast cell protease I ...
Invitrogen Anti-Mast Cell Chymase Recombinant Monoclonal (JB74-32), Catalog # MA5-34663. Tested in Western Blot (WB) and ... Protein Aliases: Alpha-chymase; Chymase; chymase 1 preproprotein transcript E; chymase 1 preproprotein transcript I; chymase 1 ... Mast Cell Chymase Recombinant Rabbit Monoclonal Antibody (JB74-32). View all (29) Mast Cell Chymase antibodies ... mast cell; chymase, heart; chymase, mast cell; mast cell; Mast cell protease I ...
Chymase mediates endothelial activation. The Preeclampsia Foundation does not necessarily endorse any research or news found in ... We speculate that activation of endothelial CLP/chymase may directly relate to the increased inflammatory phenotypic changes in ... These observations suggest that placental-derived CLP/chymase is responsible for inducing endothelial inflammatory phenotypic ...
Crystal structure of a complex of human chymase with its benzimidazole derived inhibitor.. [Yoshiyuki Matsumoto, Shinji Kakuda ... The crystal structure of human chymase complexed with a novel benzimidazole inhibitor, TJK002, was determined at 2.8 Å ... study shows that the benzimidazole inhibitor forms a non-covalent interaction with the catalytic domain of human chymase. The ...
... chymase 1, mast cell) for IHC-P, WB. Anti-Mast Cell chymase pAb (GTX105829) is tested in Human, Mouse samples. 100% Ab- ... "chymase, heart antibody", alpha-chymase antibody, "chymase, mast cell antibody", chymase 1 preproprotein transcript I antibody ... chymase 1 preproprotein transcript E antibody, "chymase 1, mast cell antibody". ... chymase 1, mast cell. Background. This gene product is a chymotryptic serine proteinase that belongs to the peptidase family S1 ...
In noninfected mice, most jejunal MCs reside in the submucosa and express mMCP-6 and mMCP-7, but not mMCP-9 or the chymase mMCP ... Reversible Expression of Tryptases and Chymases in the Jejunal Mast Cells of Mice Infected with Trichinella spiralis. Daniel S ... Nevertheless, it remained to be determined whether these immune cells could modify their expression of other chymases and the ... Reversible Expression of Tryptases and Chymases in the Jejunal Mast Cells of Mice Infected with Trichinella spiralis ...
Compound was evaluated for its inhibitory activity against human Serine protease chymase. ...
A Dual Inhibitor of the Leukocyte Proteases Cathepsin G and Chymase with Therapeutic Efficacy in Animals Models of Inflammation ... Ligand 1 occupies the S(1) and S(2) subsites of cathepsin G and chymase similarly, with the 2-naphthyl in S(1), the 1-naphthyl ... In cathepsin G, this group occupies the hydrophobic S(3)/S(4) subsites, whereas in chymase, it does not; rather, it folds onto ... These findings demonstrate that it is possible to inhibit both cathepsin G and chymase with a single molecule and suggest an ...
Chymase, a potent secretagogue for airway gland serous cells, is stored in secretory granules and released from mast cells ... Chymase released together with proteoglycans from activated mast cells caused secretion comparable to that caused by purified ... Mast cell proteoglycans modulate the secretagogue, proteoglycanase, and amidolytic activities of dog mast cell chymase.. C P ... Although the secretagogue and proteoglycanase activities of chymase are inhibited by most classes of mast cell granule- ...
Chymase and CPA digestion. Lipid-free apoA-I and HDL3 were incubated with human skin MC chymase (Elastin Products Company) and ... Lipid-free apoA-I treated with chymase and chymase/CPA for 4 h were also analysed by MALDI-TOF-MS. Two groups of peaks with m/z ... Immunohistochemical identification of chymase and CPA. To assess the presence of chymase and MC-CPA in advanced atherosclerotic ... Chymase and MC-CPA act cooperatively as follows: chymase cleaves a protein at the carboxyl side of aromatic amino acids, ...
Role of mast cells and chymase-like proteases. These studies determined whether perivascular mast cells and chymase-like ... 1990) Mast cell chymase potentiates histamine-induced wheal formation in the skin of ragweed-allergic dogs. J Clin Invest 86: ... We suggest that inhibitors of mast cell chymase-like protease(s) could be beneficial in the treatment of early-phase E. coli ... This response is modulated by E. coli LPS stimulation of perivascular mast cells to release an AT II-producing chymase-like ...
Human mast cells are classified into two groups: tryptase- and chymase-positive mast cells, and tryptase-positive and chymase- ... Measurement of PCNA-positive cells, chymase-positive cells, and mast cells. We counted PCNA-positive cells, chymase-positive ... We also reported that chymase promoted cell proliferation of fibroblasts using canine Tenons capsule, while chymase inhibitor ... a chymase inhibitor suppressed the proliferation of the fibroblasts [17]. In this study, we tested the hypothesis that chymase ...
Chymase Inhibition in Acute Myocardial Ischemia. Shizu Oyamada, Cesario Bianchi, Shinji Takai, Louis M. Chu and Frank W. Sellke ... Chymase Inhibition in Acute Myocardial Ischemia. Shizu Oyamada, Cesario Bianchi, Shinji Takai, Louis M. Chu and Frank W. Sellke ... Chymase Inhibition Reduces Infarction and Matrix Metalloproteinase-9 Activation and Attenuates Inflammation and Fibrosis after ... Chymase Inhibition Reduces Infarction and Matrix Metalloproteinase-9 Activation and Attenuates Inflammation and Fibrosis after ...
Mast Cell Chymase antibody LS-C396424 is a biotin-conjugated rabbit polyclonal antibody to human Mast Cell Chymase (CMA1). ... Mast Cell Chymase antibody LS-C396424 is a biotin-conjugated rabbit polyclonal antibody to human Mast Cell Chymase (CMA1). ... Mast Cell Chymase antibody LS-C396424 is a biotin-conjugated rabbit polyclonal antibody to human Mast Cell Chymase (CMA1). ...
Severity of DENV-induced disease in humans is linked to the MC product chymase.. (A) Graph depicts the chymase concentration in ... 3E: What is/are the point/s to make from the data of Figure 6C that show the difference between chymase levels in primary DHF ... 3C: In order to make a statement that blood chymase levels can predict the development of DHF at early phase of the disease, ... 3D: Figure 6B: the data should be presented as individual chymase blood levels in each patient rather than the average of fold ...
... to compare plasma chymase levels in various cardiovascular diseases, 5) to determine the association between plasma chymase ... to determine clinical significance of plasma chymase measurement, 3) to develop RIA method for human chymase to handle massive ... Plasma chymase levels significantly increased in systemic inflammatory diseases (pneumonia autoimmune disease and etc.) Mild ... Publications] Pfeufer et al.: Chymase gene locus is not associated with myocardial infarction and is not linked to heart size ...
Chymase inhibition reduces infarction and matrix metalloproteinase-9 activation and attenuates inflammation and fibrosis after ... Chymase inhibition reduces infarction and matrix metalloproteinase-9 activation and attenuates inflammation and fibrosis after ... Chymase inhibition reduces infarction and matrix metalloproteinase-9 activation and attenuates inflammation and fibrosis after ...
Mast Cell Chymase antibody LS-B12242 is an unconjugated mouse monoclonal antibody to human Mast Cell Chymase (CMA1). Validated ... Mast Cell Chymase antibody LS-B12242 is an unconjugated mouse monoclonal antibody to human Mast Cell Chymase (CMA1). Validated ... Mast Cell Chymase antibody LS-B12242 is an unconjugated mouse monoclonal antibody to human Mast Cell Chymase (CMA1). Validated ... Binding of this antibody to chymase is not reduced in the presence of heparin, suggesting that the antibody does not bind to ...
... chymase-negative) and MCTC (tryptase-positive, chymase-positive) types utilizing a biotinylated murine anti-chymase monoclonal ... The B7 MAb also was used to show the selective presence of chymase in mast cells. The distribution of MCT and MCTC cells in ... Detection of MCT and MCTC Types of Human Mast Cells by Immunohistochemistry Using New Monoclonal Anti-tryptase and Anti-chymase ... Detection of MCT and MCTC Types of Human Mast Cells by Immunohistochemistry Using New Monoclonal Anti-tryptase and Anti-chymase ...
  • Furthermore, both chymase inhibitors and AT 1 receptor blockers abrogate LPS-induced responses [ 8 ], indicating a potential role for hamster chymase in the pathophysiology of septic shock. (medsci.org)
  • 8 ] showed that suffusion of LPS on the in situ hamster spinotrapezius muscle for 60 min elicits an immediate, reversible biphasic vasomotor response, vasoconstriction followed by vasodilatation, and increased accumulation of perivascular mast cells having chymase-like activity. (medsci.org)
  • We examined the effects of overexpressed human chymase on survival and activity in lipopolysaccharide (LPS)-treated mice. (medsci.org)
  • These data suggest a possible contribution of human chymase activation to LPS-induced mortality. (medsci.org)
  • However, whether a similar role exists for human chymase has not been established. (medsci.org)
  • We sought to investigate the possible contribution of human chymase to LPS-induced mortality. (medsci.org)
  • Therefore, survival rate and chymase activity in the heart and skin were measured in transgenic mice carrying the human chymase gene [ 9 ]. (medsci.org)
  • The experiment was performed in male transgenic mice (18-20 weeks of age) carrying the human chymase gene (Tg) [ 9 ] and male wild-type C57BL/6 mice (WT). (medsci.org)
  • Preparation of the human chymase transgene and production of Tg mice were described previously in detail [ 9 ]. (medsci.org)
  • BACKGROUND: The left ventricular (LV) dilatation of isolated mitral regurgitation (MR) is associated with an increase in chymase and a decrease in interstitial collagen and extracellular matrix. (lvhn.org)
  • Thus, we hypothesize that chymase inhibitor (CI) will attenuate extracellular matrix loss and LV remodeling in MR. (lvhn.org)
  • Endothelin-converting enzymes (ECE), chymases, and non-ECE metalloproteases are responsible for the synthesis of ET-1 by means of autocrine regulation (Lüscher 2434). (georgetown.edu)
  • LPS-induced increases in chymase activity in the heart and skin were significantly greater in Tg than WT mice. (medsci.org)
  • Basal chymase activity in the heart and skin ( n =6, respectively) was measured in eighteen-week-old Tg and age-matched WT mice. (medsci.org)
  • This idea provoke further research into the initiation of various biochemical pathways by limited proteolysis, such as prothrombin activation by mast cell tryptase histamine release by mast cell chymase, and initiation of influenza virus entry by tryptase Clara. (wikibooks.org)
  • Chymase Inhibition Prevents Fibronectin and Myofibrillar Loss and Impr" by Betty Pat, Yuanwen Chen et al. (lvhn.org)
  • Chymase Inhibition Prevents Fibronectin and Myofibrillar Loss and Improves Cardiomyocyte Function and LV Torsion Angle in Dogs with Isolated Mitral Regurgitation. (lvhn.org)
  • CONCLUSIONS: These results suggest that chymase disrupts cell surface-fibronectin connections and FAK phosphorylation that can adversely affect cardiomyocyte myofibrillar structure and function. (lvhn.org)
  • In addition to profibrotic effects, chymase has significant antifibrotic actions because it activates matrix metalloproteinases and kallikrein and degrades fibronectin. (lvhn.org)
  • This study aimed to examine the association between chymase 1 gene (CMA1) polymorphisms and atrial fibrillation (AF) in a Chinese Han population. (cdc.gov)
  • Structure, chromosomal assignment, and deduced amino acid sequence of a human gene for mast cell chymase. (rcsb.org)
  • Conclusions -Tranilast suppressed chymase gene expression, which was specifically activated in the injured arteries, and prevented neointima formation. (ahajournals.org)
  • Therefore, survival rate and chymase activity in the heart and skin were measured in transgenic mice carrying the human chymase gene [ 9 ]. (medsci.org)
  • The experiment was performed in male transgenic mice (18-20 weeks of age) carrying the human chymase gene (Tg) [ 9 ] and male wild-type C57BL/6 mice (WT). (medsci.org)
  • Phylogenetic analyses place one of the opossum genes firmly with mast cell α-chymases, which indicates that the α-chymase had already evolved as a separate, clearly identifiable gene before the separation of marsupials and placental mammals. (diva-portal.org)
  • This previously published "granzyme" does not cluster clearly with any of the chymase locus gene families, but shares the absence of the Cys 191 -Cys 220 bridge with the other chymase locus proteases. (diva-portal.org)
  • Chymase gene locus is not associated with myocardial infarction and is not linked to heart size or blood pressure'Am J Cardiol. (nii.ac.jp)
  • Association between chymase gene polymorphisms and atrial fibrillation in Chinese Han population. (cdc.gov)
  • A chymase gene variant is associated with atherosclerosis in venous coronary artery bypass grafts. (cdc.gov)
  • Because chymase is synthesized mainly in mast cells, we assumed that the chymase-dependent ANG II formation could be downregulated by tranilast, a mast cell-stabilizing antiallergic agent. (ahajournals.org)
  • The crystal structure of human chymase complexed with a novel benzimidazole inhibitor, TJK002, was determined at 2.8 Å resolution. (sigmaaldrich.com)
  • Thus, mast cells are the source of the vascular ACE-independent pathway, and the antihypertensive benefit of combining ACE inhibitor therapy with AT(1) receptor antagonist therapy is most likely due to negation of chymase-catalyzed Ang II generation. (nih.gov)
  • Balloon injury remarkably activated canine vascular chymase, 10 and an ANG II receptor antagonist substantially prevented neointima formation, whereas an ACE inhibitor did so only modestly. (ahajournals.org)
  • Crystal structure of a complex of human chymase with its benzimidazole derived inhibitor. (sigmaaldrich.com)
  • The X-ray crystallographic study shows that the benzimidazole inhibitor forms a non-covalent interaction with the catalytic domain of human chymase. (sigmaaldrich.com)
  • RWJ-355871) as a novel, potent dual inhibitor of neutrophil cathepsin G (K(i) = 38 nm) and mast cell chymase (K(i) = 2.3 nm). (rcsb.org)
  • Chymase inhibitor drugs would work by allowing IGF-1, produced by the injured heart, to last longer. (emory.edu)
  • A clinical trial using a chymase inhibitor in heart failure patients is underway in Europe. (emory.edu)
  • Because lethal arrhythmias are generally believed to contribute to sudden cardiac death, we assessed whether inhibition of cardiac chymase would provide an antiarrhythmic effect during the 8-h ischemic period after 2-[4-(5-fluoro-3-methylbenzo[b]thiophen-2-yl)sulfonamide-3-methanesulfonylphenyl]oxazole-4-carboxylicacid (TY51184) (a specific chymase inhibitor, 1 mg/kg i.v.) treatment by ligation of left anterior descending coronary artery (LAD) in dogs. (spotidoc.com)
  • Thus, we hypothesize that chymase inhibitor (CI) will attenuate extracellular matrix loss and LV remodeling in MR. (lvhn.org)
  • X-ray structure of human chymase in complex with small molecule inhibitor. (proteopedia.org)
  • Comparison of the extended specificity results to a panel of mammalian mast cell chymases show, in almost all aspects, the same cleavage characteristics. (usda.gov)
  • Chymases (EC 3.4.21.39) are mast cell serine proteinases that are variably expressed in different species and, in most cases, display either chymotryptic or elastolytic substrate specificity. (proteopedia.org)
  • Subtle variations in the residues in the active site that are already known to influence chymase substrate specificity can also strongly affect the compound potency. (proteopedia.org)
  • Human mast cells are classified into two groups: tryptase- and chymase-positive mast cells, and tryptase-positive and chymase-negative mast cells. (molvis.org)
  • RESULTS -Subcutaneous adipose biopsies showed an elevated population of tryptase-positive, chymase-positive degranulated mast cells. (diabetesjournals.org)
  • CONCLUSIONS -Tryptase-positive/chymase-postitive mast cells, known to be sensitive to sodium cromolyn, may contribute to the destructive immune process mediated in response to exogenous insulin. (diabetesjournals.org)
  • 15 These results indicate that chymase contributes to the pathogenesis of intimal hyperplasia by augmenting the local ANG II production to a greater extent than does ACE. (ahajournals.org)
  • These results indicate that chymase treatment of HDL3 specifically impairs the ABCA1-dependent pathway without influencing either aqueous or SR-BI-facilitated diffusion and that this effect is caused by depletion of lipid-poor pre-β-migrating particles in HDL3. (unimi.it)
  • The original objectives of the project was 1) to develop Westernblot analysis and biochemical assay for plasma human chymase, 2) to determine clinical significance of plasma chymase measurement, 3) to develop RIA method for human chymase to handle massive clinical samples, 4) to compare plasma chymase levels in various cardiovascular diseases, 5) to determine the association between plasma chymase level and various cardiovascular diseases. (nii.ac.jp)
  • Plasma chymase levels significantly increased in systemic inflammatory diseases (pneumonia autoimmune disease and etc. (nii.ac.jp)
  • Moreover, humans with kidney disease express chymase in diseased blood vessels in concordance with significantly elevated plasma chymase levels. (northwestern.edu)
  • Recombinant human Chymase protein. (lsbio.com)
  • Therefore, we establish a double sandwich ELISA using monoclonal and polyclonal antibodies for recombinant human chymase. (nii.ac.jp)
  • 490 Downloaded from jpet.aspetjournals.org by guest on June 9, 2014 ABSTRACT Chymase plays an important role in the regulation of local angiotensin (Ang) II formation in the cardiac tissue. (spotidoc.com)
  • Studies in humans support the pathologic role of chymase in diabetic nephropathy, while animal studies form the basis for the importance of increased chymase-dependent angiotensin II formation in progressive hypertensive, diabetic and inflammatory nephropathies. (northwestern.edu)
  • CONCLUSIONS: These results suggest that chymase disrupts cell surface-fibronectin connections and FAK phosphorylation that can adversely affect cardiomyocyte myofibrillar structure and function. (lvhn.org)
  • Here we show that the predominant chymase mRNA species in the mouse aorta are those for types 4 and 5 isoforms, and that both are efficient Ang II-forming enzymes. (nih.gov)
  • 7 8 9 10 11 Chymases of these species cleave the Phe 8 -His 9 bond of ANG I and produce ANG II efficiently. (ahajournals.org)
  • To better understand mast cell functions in these species, one member of the mouse Mcpt8-family, mMCP-8, and human and dog chymase were studied. (diva-portal.org)
  • 1990). Therefore, cardiac chymase may play an important role in the pathogenesis of the Ang II-related heart diseases in such species. (spotidoc.com)
  • Compounds were 10-300-fold less potent, and in some instances ineffective, against chymases from the other species. (proteopedia.org)
  • Recombinant protein encompassing a sequence within the center region of human Mast Cell Chymase. (genetex.com)
  • MC chymase cleaves apoA-I (apolipoprotein A-I), the main protein component of HDL (high-density lipoprotein). (portlandpress.com)
  • There was a significant positive correlation between plasma chymase level and plasma c-reactive protein or fibrinogen. (nii.ac.jp)
  • The amino acid sequence of human skin chymase was established by protein methods and by analysis of PCR amplification products obtained with cDNA-derived from urticaria pigmentosa (UP) lesions. (duke.edu)
  • This sequence, along with that established for the purified protein, constituted 99% of the heart chymase primary structure, strongly indicating that human skin and heart chymases have identical primary structures. (duke.edu)
  • The side chains of residues Phe191 and Lys192 of pro-chymase fill the Ile16 binding pocket and the base of the S1 binding pocket, respectively. (rcsb.org)
  • CPA, in vitro , further cleaved C-terminal Phe 225 and Phe 229 residues newly exposed by chymase, but did not cleave Tyr 192 . (portlandpress.com)
  • The amino acid sequences for these peptides combined with the sequence obtained for the protein's NH2-terminal region (35 residues) accounted for 137 residues of the human skin chymase sequence. (duke.edu)
  • The amino acid sequence (135 residues) deduced from this product was identical to that of heart chymase in the region between the primers. (duke.edu)
  • MA5-11717 targets Mast Cell Chymase in IHC (P) and WB applications and shows reactivity with Human samples. (thermofisher.com)
  • A decrease in plasma Ang II levels after TY51184 treatment occurred concomitantly with suppression of cardiac chymase activity. (spotidoc.com)
  • these associations, with the exception of cardiac chymase A AA polymorphism (p = 0.06), remained significant in multivariate analysis. (bmj.com)
  • Evaluation of ACE-dependent and ACE-independent Ang II-forming pathways in mast cell-deficient (Kit(w)/Kit(w-v)) mice and their mast cell-sufficient littermate (MC(+/+)) controls revealed that, in contrast to the latter, Kit(w)/Kit(w-v) mice fail to express chymase mRNAs in the vasculature and have almost no ACE-independent Ang II-forming activity in either isolated blood vessels or homogenates. (nih.gov)
  • Background -Activation of vascular chymase plays a major role in myointimal hypertrophy after vascular injury by augmenting the production of angiotensin (ANG) II. (ahajournals.org)
  • Mast cells contain a number of preformed chemicals mediators such as histamine, chymase, carboxypeptidase and proteolytic tryptase. (abcam.com)
  • In contrast, mast cell number, percentage, and the chymase-positive phenotype increased in small airway regions. (nih.gov)
  • In contrast, rats possess only an ACE-dependent Ang II-forming pathway, because in cardiovascular tissues in rat, chymase acts as an This study was supported by Grant-in-Aid 13670102 (C) for Scientific Research from the Ministry of Education, Science, Sports and Culture, Japan. (spotidoc.com)
  • In contrast to the human, mouse, hamster and opossum chymases that show a relatively strong preference for negatively charged amino acids in the P2′position, the sheep MCP2, however, lacked that preference. (usda.gov)
  • In contrast, efflux of free cholesterol from Fu5AH to chymase-treated and to untreated HDL 3 was similar. (unimi.it)
  • After the analysis was adjusted for multiple comparisons, only chymase-positive mast cells significantly and positively correlated with lung function. (nih.gov)
  • LPS-induced increases in chymase activity in the heart and skin were significantly greater in Tg than WT mice. (medsci.org)
  • Densities of proliferative cell nuclear antigen-positive cells, chymase-positive cells, and areas of collagen fiber in conjunctival and scleral lesions were significantly decreased in MMC-treated eyes, compared with placebo-treated eyes (p=0.034, 0.034, 0.049, respectively). (molvis.org)
  • In the diabetic kidney, while ACE expression was significantly upregulated (1 to 3-fold) by tubular epithelial cells (TEC) and infiltrating mononuclear cells, there was also markedly increased chymase expression (10 to 15-fold) by both MC and VSMC, with strong deposition in the collagen-rich extracellular matrix including both diffuse and nodular glomerulosclerosis, tubulointerstitial fibrosis, and vascular sclerosis. (asnjournals.org)
  • Total Ang II-forming activity and chymase activity in the infarcted heart were increased significantly 8 h after LAD ligation. (spotidoc.com)
  • In addition, differential expression of ACE and chymase in the diabetic kidney indicates that both ACE and chymase may be of equal importance for AngII-mediated diabetic nephropathy and vascular disease. (asnjournals.org)
  • We speculate that activation of endothelial CLP/chymase may directly relate to the increased inflammatory phenotypic changes in the vascular system in women with PE. (preeclampsia.org)
  • Previously we demonstrated that chymase contributed to ANG II formation in human, monkey, and dog vascular tissues. (ahajournals.org)
  • Mast cells (MCs) are activated in vivo during DENV infection, and we show that this elevates systemic levels of their vasoactive products, including chymase, and promotes vascular leakage. (elifesciences.org)
  • In the normal kidney, while ACE was constitutively expressed by most kidney cells, chymase was weakly expressed by mesangial cells (MC) and vascular smooth muscle cells (VSMC) only. (asnjournals.org)
  • As assessed immunohistochemically, we now show that MCs reversibly change their expression of the recently described chymase mMCP-9 and both tryptases as these cells traverse the jejunum during the amplification and regression stages of the reactive MC hyperplasia. (jimmunol.org)
  • GAPDH-normalized chymase 1, chymase 2, chymase 4, and chymase 5 mRNA levels in aortae from vehicle- or captopril-treated MC +/+ and Kit w /Kit w-v mice. (nih.gov)
  • Chymase mRNA levels and chymaselike activity of vehicle-treated injured arteries were increased 10.2- and 4.8-fold, respectively, those of uninjured arteries. (ahajournals.org)