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food industry
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when milk casein is hydrolyzed at 37°C by using commercial digestive enzymes, pancreatin F and protease A, a significant accumulation of L-ornithine in the hydrolysate and the simultaneous disappearance of L-arginine is noted. Transient but distinct arginase activity, which is sufficiently high for L-ornithine production, is detected in the hydrolysate for a certain period during casein hydrolysis. Findings suggest that an inactive precursor of arginase is contaminated in pancreatin F and is proteolytically activated during the incubation
nutrition
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oopherectomized animals treated with 0.5% cholesterol-enriched diet. Diet results in increase in plasma lipids, atheromatous lesions as well as expression of enzyme isoforms arginase I and II and an increase in cellular proliferation. Diet plus supplementation of 17beta-estradiol results in a decrease of atheromatous lesions and reduced expression of both enzyme isoforms and inducible NO synthase
pharmacology
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enzyme is a target for inhibitor design based on arginine analogues with uncharged, tetrahedral functional groups
analysis
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specific detection of NO production in intact mouse tissue, inhibition of enzyme by N-hydroxy-nor-L-arginine to avoid disturbances
analysis
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arginase activity may interfere in nitric oxide activity assay. A nitric oxide synthase-independent radioactive signal in mitochondrial samples analyzed for nitric oxide synthase-catalyzed [14C]-L-arginine to [14C]-L-citrulline conversion is due to the arginase-catalyzed conversion of [14C]-L-arginine to [14C]-urea. The results, in addition to reconfirming the absence of nitric oxide synthase activity in rat liver MT, show the need to include arginase inhibitors in studies using mitochondrial samples in order to avoid confounding results when using nitric oxide synthase activity assays
analysis
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assay method based on a combination of moderately selective host-guest binding with the specificity of enzymatic transformations which allows the real-time monitoring of enzymatic reactions in a homogeneous solution. The resulting supramolecular tandem assays exploit the dynamic binding of a fluorescent dye with a macrocyclic host in competition with the binding of the substrate and product. The depletion of the substrate allows the fluorescent dye to enter the macrocycle in the course of the enzymatic reaction, which leads to the desired fluorescence response. For arginase, p-sulfonatocalix[4]arene is used as the macrocycle, which displays binding constants of 6400 per M with arginine, 550 per M with ornithine, and 60 000 per M with the selected fluorescent dye 1-aminomethyl-2,3-diazabicyclo[2.2.2]oct-2-ene, the dye shows a weaker fluorescence in its complexed state, which leads to a switch-off fluorescence response in the course of the enzymatic reaction. Assays can be successfully used to probe the inhibition of enzymes
analysis
development of a high-throughput semiquantitative assay system using a colorimetric 96-well plate assay to monitor the formation of urea. The assay has a dynamic range of about 5-300 microM for the ureido product
drug development
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the application of rhArg-PEG alone or in combination with existing chemotherapeutic drugs may represent a specific and effective therapeutic strategy against human hepatocellular carcinoma
drug development
arginase catalyzes the first committed step in the biosynthesis of polyamines that enable cell growth and hence potential drug target for the treatment of leishmaniasis
medicine
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enzyme is a target for inhibitors used in therapeutic treatment of smooth muscle disorders, such as erectile dysfunction
medicine
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agents that elevate cAMP level significantly enhance induction of enzyme by cytokines. Consequences of increased enzyme expression should be evaluated when phosphodiesterase inhibitors are used for treatment of inflammatory disorders in which IL-4 and/or TGF-beta predominate
medicine
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enzyme is involved in T-cell function during infection. Helicobacter pylori extracts and intact Helicobacter pylori of wild-type, but not of enzyme deficient mutant, induce a decreased expression of CD3zeta-chain of the TCR in Jurkat cells and reduce proliferation of freshly isolated human normal T-lymphocytes
medicine
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H2O2 specifically impairs endothelium-dependent NO-mediated dilation of coronary microvessels by reducing L-arginine availability through upregulation of enzyme
medicine
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in coronary arteriole, enzyme activity increases twofold with hypertension. Inhibition of enzyme activity by Nomega-hydroxy-nor-L-arginine or incubation with L-arginine partially restores NO release and dilation to adenosine in hypertrophic vessels
medicine
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oopherectomized animals treated with 0.5% cholesterol-enriched diet. Diet results in increase in plasma lipids, atheromatous lesions as well as expression of enzyme isoforms arginase I and II and an increase in cellular proliferation. Diet plus supplementation of 17beta-estradiol results in a decrease of atheromatous lesions and reduced expression of both enzyme isoforms and inducible NO synthase. Inhibiton of enzyme expression by 17beta-estradiol as mechanism in attenuating atherogenensis
medicine
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patients with cystic fibrosis, before and after 14 days of antibiotic treatment for pulmonary exacerbation. Systemic enzyme levles are significantly increased in cystic fibrosis with exacerbation. Enzyme levels normalize with antibiotic treatment. Plasma L-arginine is reduced before, but not after treatment, L-ornithine, L-proline, and L-glutamic acid are normal before and increased after treatment
medicine
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plasma arginase activity is significantly elevated in patients with sickle cell disease, with highest activity found in patients with secondary pulmonary hypertension. Arginase activity correlates with the arginine-ornithine ratio, and lower ratios are associated with greater severity of pulmonary hypertension and with mortality. Increased plasma enzyme activity is correlated with increased intravascular hemolytic rate and, to a lesser extent, with markers of inflammation and soluble adhesion molecule levels
medicine
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rejection of skin xenografts, but not allografts, is associated with a local high production of Th2 cytokines IL-4 and IL-10, overexpression of enzyme, strongly enhanced enzyme activity and attenuated NO generation in the graft. Upregulation of enzyme activity limits the bioavailability of L-arginine for the inducible NO synthase and thus attenuates generation of NO by the graft-infiltrating macrophages
medicine
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significant decrease of enzyme activity during 7th-21st day of gestation, significant increase in enzyme activity at term gestation, day 22. Gestational changes in enzyme activity negatively correlate with those in cyclic GMP production and positively correlate with those in endogenous NO synthase inhibitors and endothelin-1 contents. Enhanced enzyme activity at term gestation may be implicated in increasing myometrial contractions mediated by increase in endothelin-1
medicine
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targeting vascular arginase as a therapeutic possibility for atherosclerosis. Thrombin enhances enzyme activity via small G-protein RhoA/ROCK in endothelial cells
medicine
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overexpression of arginase in the penis contributes to erectile dysfunction
medicine
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arginase gene expression in the lung is linked to asthma both in clinical studies of human patients and in the well-studied mouse model of ovalbumin-induced airway inflammation
medicine
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enzyme serves as a therapeutic target for the treatment of asthma, erectile dysfunction, and atherosclerosis
medicine
enzyme serves as a therapeutic target for the treatment of asthma, erectile dysfunction, and atherosclerosis
medicine
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new forms of efficient arginase inhibitors, could be useful as therapeutic regimen in hemoglobinopathies and other related inflammation-mediated diseases
medicine
a significant decrease in arginase activity, dependent of the liver clinical stage, is observed in cirrhotic tissue. Arginase AI activity and its mRNA level are significantly decreased in cirrhotic liver, whereas the activity and expression of arginase AII are concurrently raised, as compared to normal liver
medicine
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bone marrow cell derived arginase I is the predominant source of allergen-induced lung arginase but is not required for allergen-induced inflammation, airway hyperresponsiveness or collagen deposition
medicine
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both ARG1 and ARG2 are expressed by hormone-sensitive and hormone-refractory prostate cancer cell lines, with the LNCaP cells having the highest arginase activity. In prostate tissue samples, ARG2 is more expressed in normal and non-malignant prostatic tissues compared to tumor tissues. Following androgen stimulation of LNCaP cells with 10 nM R1881, both ARG1 and ARG2 are overexpressed. The regulation of arginase expression following androgen stimulation is dependent on the androgen receptor. This observation is correlated in vivo in patients by immunohistochemistry. Patients treated by androgen-deprivation therapy prior to surgery have lower ARG2 expression in both nonmalignant and malignant tissues. ARG1 and ARG2 are enzymatically active and their decreased expression by siRNA results in reduced overall arginase activity and L-arginine metabolism. The decreased ARG1 and ARG2 expression also translates with diminished LNCaP cells cell growth and increased peripheral blood mononuclear cell activation following exposure to LNCaP cells conditioned media. Interleukin-8 is also upregulated following androgen stimulation and it directly increases the expression of ARG1 and ARG2 in the absence of androgens
medicine
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coinhibitory and costimulatory molecules PD-1 and CTLA-4 on the Gr-1+CD11b+ myeloid-derived suppression cells regulate the activity and expression of arginase I. The blockage and silencing of PD-1, CTLA-4 or both PD-1 and CTLA4 molecules can significantly reduce arginase I activity and expression induced with tumor-associated factor. Similar results are also observed while their ligands B7-H1 and/or CD80 are blocked or silenced. CD80 deficiency also decreases the arginase I expression and activity. Antibody blockade or silencing of PD-1, CTLA-4 or both reduces the suppressive potential of PD-1+CTLA-4+ myeloid-derived suppression cells. Blockade of PD-1, CTLA-4 or both also slows tumor growth and improves the survival rate of tumor-bearing mice
medicine
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comparison of the infectivity of arg- and wild-type Plasmodium berghei by inoculation of mice using sporozoites dissected from mosquito salivary glands shows a significant reduction in infectivity in the arg- strain 40 h postinfection
medicine
Co2+ substitution of the Mn2+ metal cofactor confers more than 10fold higher catalytic activity and 5fold greater stability. Based on the hypothesis that the Co-ArgI enzyme would decrease tumor burden by systemic elimination of L-arg in a murine model, Co-hArgI was conjugated to 5-kDa PEG to enhance circulation persistence and applied as monotherapy for hepatocellular carcinoma and pancreatic carcinoma in vitro and in vivo murine xenografts. Weekly treatment of 8 mg/kg Co-hArgI-PEG effectively controls human HepG2 and Panc-1 tumor xenografts. Both cell lines underwent apoptosis in vitro with significant increased expression of activated caspase-3 and showed evidence of autophagy in vitro and in vivo
medicine
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exposure to ONOO- generator SIN-1 or to H2O2 increases arginase I expression and arginase activity by 35% and 50%, respectively, which is prevented by ROCK inhibitor, Y-27632, PKC inhibitor, Gö6976 or siRNA to p115-Rho GEF. The oxidative species ONOO- and H2O2 increase arginase activity/expression through PKC-mediated activation of RhoA/Rho kinase pathway
medicine
inhibition of Leishmania arginase leads to a decrease in parasite growth and infectivity and thus represents an attractive therapeutic strategy
medicine
Leishmania arginase is a potential drug target for the treatment of leishmaniasis because this binuclear manganese metalloenzyme initiates de novo polyamine biosynthesis by catalyzing the hydrolysis of L-arginine to generate L-ornithine and urea. The product L-ornithine subsequently undergoes decarboxylation to yield putrescine, which in turn is utilized for spermidine biosynthesis. Polyamines such as spermidine are essential for the growth and survival of the parasite, so inhibition of enzymes in the polyamine-biosynthetic pathway comprises an effective strategy for treating parasitic infections
medicine
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overexpression of arginase in the penis contributes to erectile dysfunction
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synthesis
the enzyme can be used to produce L-ornithine from L-arginine
synthesis
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the enzyme can be used to produce L-ornithine from L-arginine
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additional information
pulmonary vascular and airway diseases in which arginase activity is increased are associated with decreased NO production and reduced smooth muscle relaxation
additional information
pulmonary vascular and airway diseases in which arginase activity is increased are associated with decreased NO production and reduced smooth muscle relaxation