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.

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 ...
To gain insight into the biological role of mast cell chymase we have generated a mouse strain with a targeted deletion in the gene for mast cell protease 4 (mMCP-4), the mouse chymase that has the closest relationship to the human chymase in terms of tissue localization and functional properties. reactions (22), and angiogenesis in hamster sponge granulomas (23). It is important to stress that although the reports described above provide evidence for an involvement of chymases in various pathological conditions, the exact mode of action for chymase has not been determined, i.e., the in vivo substrates for chymases have not been identified. Further, limited knowledge is available as regards the individual contribution of the various MC chymases. To gain further insight into the biological role of MC chymase we have here inactivated the gene for mMCP-4. Materials and Methods Reagents. The chromogenic peptide substrates S-2586, S-2238 and S-2288 were from Chromogenix. The CPA substrate M-2245 ...
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. ...
Mouse mast cell protease-4 (mMCP-4) has been associated with autoimmune and inflammatory illnesses although the precise systems underlying its function in these pathological circumstances remain unclear. impaired in cultured mMCP-4?/? MCs and in your skin of pathogenic IgG-injected mMCP-4?/? mice. MMP-9 activation had not been AS-252424 completely restored by regional reconstitution with WT or mMCP-4?/? PMNs. Local reconstitution with mMCP-4+/+ MCs but not with mMCP-4?/? MCs restored blistering MMP-9 activation and PMN recruitment in mMCP-4?/? mice. mMCP-4 also degraded the hemidesmosomal transmembrane protein BP180 AS-252424 both in the skin and (1% 1 cm) = 13.6). The titers of anti-murine BP180 antibodies in both the unfractionated rabbit serum and in the purified IgG portion were assayed by indirect immunofluorescence (IF) using mouse pores and skin cryosections as substrate. The antibody preparations were also tested by immunoblotting against the GST-mBP180ABC fusion protein. The IF and ...
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 ...
MONOSAN item MON8101 Mouse anti Mast Cell Chymase, clone CC1 (Monoclonal), 100 ug. Contact us for more information about item MON8101.
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 ...
hi. Check this pdf. Authors proclaim it to be a specific chymase inhibitor but the full text article is not accessible. Check If you can access the same and figure out its availability.. http://jpet.aspetjournals.org/content/304/2/841.abstract. ...
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 ...
Expulsion of gastrointestinal nematodes is associated with pronounced mucosal mast cell (MMC) hyperplasia, differentiation, and activation, accompanied by the s
Fingerprint Dive into the research topics of Purification and identification of two serine class proteinases from dog mast cells biochemically and immunologically similar to human proteinases tryptase and chymase. Together they form a unique fingerprint. ...
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 ...
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, ...
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 ...
Chymostatin (N-(Nα -Carbonyl-Cpd-X-Phe-al)-Phe (Cpd = capreomycidine) (capreomycidine = [S,S]-α -(2-Iminohexahydro-4-pyrimidyl)glycine)); microbial No;
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 ...

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