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Results for “ARGINASE”

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PubMed2002

Immunoregulation during disease progression in prediabetic NOD mice: inverse expression of arginase and prostaglandin H synthase 2 vs. interleukin-15.

Non-obese diabetic (NOD) mice spontaneously develop insulin dependent diabetes due to autoimmune destruction of beta-cells. The progression of insulitis can be accelerated and synchronized in the pancreas by a single injection of 250 mg/kg cyclophosphamide. In this study, we will report on three immune mediators that were not known to be expressed during insulitis until now. Early insulitis in ten-week-old female NOD mice was associated with strong expression of prostaglandin H synthase 2 in the pancreas and of arginase, an antagonist enzyme of the inducible NO synthase. After acceleration of insulitis progression by cyclophosphamide, expression of the two enzymes was downregulated within 24 h. There was strong concomitant upregulation of IL-15 gene expression that preceded lymphocyte invasion of islets and a rise of IFN-gamma mRNA levels by several days. The comparison of individual pancreata showed that the expression of IL-12 and IL-18 mRNA closely correlated with levels of IL-15 gene expression. We conclude that arginase and prostaglandin H synthase 2 expression is associated with peri-insulitis, while IL-15 is a candidate cytokine in driving destructive insulitis, as it elicits Th1-cytotoxic responses in lymphoid as well as in non-lymphoid immune cells and is unusually resistant to downregulation by antagonistic cytokines. This is the first report on arginase, prostaglandin H synthase 2 and IL-15 expression in pancreatic lesions of prediabetic NOD mice.

Animals↗

PubMed2003

Arginase activity is a useful marker of nitrogen limitation during alcoholic fermentations.

Nitrogen deficiency in musts is one of the causes of sluggish or stuck fermentations. In this work we propose that arginase activity determination can be useful for detecting nitrogen starvation early in vinification. CAR1 and YGP1 genes are not specifically induced under conditions of nitrogen starvation. However, a significant increase in the enzymatic activity of arginase, the product of the CAR1 gene, is detected in vinifications carried out with musts containing limiting amounts of nitrogen. Moreover, on adding ammonia to a nitrogen-deficient vinification, even at late stages, this enzymatic activity is repressed, and growth rate is restored simultaneously. We also investigate the role of ethanol toxicity in nitrogen starvation. The results suggest that ethanol produced during vinification or exogenously added up to 8% (v/v) concentration does not cause nitrogen starvation under the conditions tested because arginase activity is not increased.

Ammonia↗

PubMed1994

Dietary manganese deficiency decreases rat hepatic arginase activity.

This study was designed to quantify the effect of dietary manganese deficiency on rat hepatic Mn concentration and arginase activity. Weanling male Sprague-Dawley rats were randomly assigned to two groups of nine rats each and fed L-amino acid diets with 0 or 48 micrograms Mn/g diet for 21 d. After 21 d, hepatic Mn concentration (mumol/g liver dry wt, mean +/- SEM) was 0.130 +/- 0.005 for the control group but was lower (P < 0.01) in the Mn-deficient group (0.040 +/- 0.003). There were no differences in the hepatic concentrations of any other measured mineral. Hepatic arginase activity [mmol ornithine/(g hepatic protein.min)] was 1.55 +/- 0.22 in the control group and was lower (P < 0.01) in the Mn-deficient group (1.12 +/- 0.26). Plasma ammonia concentration was 301 +/- 6 mumol/L in the control group and was higher (P < 0.01) in the Mn-deficient group (480 +/- 8 mumol/L). In contrast, plasma urea concentration was higher (P < 0.01) in the control group (350 +/- 10 mumol/L) than in the Mn-deficient group (267 +/- 7 mumol/L). There were no differences in plasma concentrations of arginine or other amino acids between the control and the Mn-deficient groups. Our results demonstrate for the first time that dietary Mn deficiency results in altered plasma concentrations of ammonia and urea in association with decreased hepatic Mn concentration and arginase activity in young growing rats.

Amino Acids↗

PubMed1994

L-Arginine deficiency after liver transplantation as an effect of arginase efflux from the graft. Influence on nitric oxide metabolism.

L-Arginine plays an important role in protecting animals against ammonia intoxication, enhances immune function, stimulates wound healing, and is the precursor for the endothelium-derived relaxing factor, recently recognized as nitric oxide (NO). In this study, we investigated the influence of hepatic reperfusion on amino acid metabolism after human OLT. After 10 sec of reperfusion, the arterial plasma levels of L-arginine dropped from 105 +/- 12 mumol/L to 3.8 +/- 0.6 mumol/L (P < 0.001), whereas plasma ornithine increased from 40 +/- 5.5 mumol/L to 129 +/- 15 mumol/L (P < 0.001). The reduced L-arginine levels remained subnormal for several hours after OLT. This drop in plasma L-arginine was due to an arginase release from the implanted graft. Immediately after reperfusion, the plasma concentrations of arginase increased from pretransplantation values of 18 +/- 13 IU/L to 2384 +/- 1456 IU/L (P < 0.01). Measurement of plasma nitrite (NO2-) and nitrate (NO3-), which are the stable end products of NO, revealed that NO2- decreased about 50% after reperfusion (from 1.64 +/- 0.32 mumol/L to 0.80 +/- 0.17 mumol/L; P < 0.001), whereas NO3- levels remained unchanged (76 +/- 23 mumol/L vs. 63 +/- 8 mumol/L). We conclude that hepatic reperfusion causes L-arginine deficiency by liberating high amounts of arginase from the implanted graft. This L-arginine depletion may influence the NO synthesis in patients after OLT.

Adult↗

PubMed1991

Genetic engineering of a sake yeast producing no urea by successive disruption of arginase gene.

Urea is reported to be a main precursor of ethyl carbamate (ECA), which is suspected to be a carcinogen, in wine and sake. In order to minimize production of urea, arginase-deficient mutants (delta car1/delta car1) were constructed from a diploid sake yeast, Kyokai no. 9, by successive disruption of the two copies of the CAR1 gene. First, the yeast strain was transformed with plasmid pCAT2 (delta car1 SMR1), and strains heterozygous for CAR1 gene were isolated on sulfometuron methyl plates. Successively, the other CAR1 gene was disrupted by transformation with plasmid pCAT1 (delta car1 G418r) and the resulting car1 mutants were isolated on a G418 plate. Arginase assay of the total cell lysate of the mutants showed that 70% of transformants isolated on G418 plates had no detectable enzyme activity, possibly as a result of the disruption of the two copies of the CAR1 gene. Further genomic Southern analysis confirmed this result. We could brew sake containing no urea with the delta car1/delta car1 homozygous mutant. It is of additional interest that no ECA was detected in the resulting sake, even after storage for 5 months at 30 degrees C. This molecular biological study suggests that ECA in sake originates mainly from urea that is produced by the arginase.

Alcoholic Beverages↗

PubMed1972

Regulation of arginase activity by intermediates of the arginine biosynthetic pathway in Neurospora crassa.

It has been found that, in Neurospora crassa, arginine synthesized from exogenous citrulline was not as effectively hydrolyzed as exogenous arginine. This was explained by the observed inhibition of arginase in vitro and in vivo by citrulline. The high arginine pool formed from exogenous citrulline feedback inhibits the arginine pathway. These two factors allow exogenous citrulline to be used adventitiously and efficiently as an arginine source. Finally, it was found that ornithine was a strong inhibitor of arginase. This suggests that the characteristically high ornithine pool of minimal cultures of Neurospora may act to control a potentially wasteful catabolism of endogenous arginine by arginase.

Arginase↗

PubMed1987

Relationship between two major immunoreactive forms of arginase in Neurospora crassa.

Two major immunoreactive proteins of Mr 41,700 and 36,100 have been detected in crude mycelial extracts with polyclonal antibodies raised against arginase purified from Neurospora crassa. The latter corresponded to the protein used to obtain the antibodies. Both polypeptides were either missing or present in very low amounts in mutant strains having little or no detectable arginase activity. The relative proportion of the two species was altered in strains containing the nitrogen catabolite regulatory mutation nit-2. Peptide mapping indicated that the two species are very closely related, but several of the peptides which appeared to be identical by staining reacted differently with the antibodies. Both species were produced by in vitro translation of poly(A)+ mRNA, although the larger species was produced to a much smaller extent than was expected from its abundance in vivo. The results suggest the existence of multiple forms of arginase in N. crassa which differ in their response to nitrogen catabolite regulation.

Arginase↗

PubMed1986

Erythrocyte arginase, pyrimidine 5'-nucleotidase (P5N), and deoxypyrimidine 5'-nucleotidase (dP5N) as indices of lead exposure.

The activities of three erythrocyte (rbc) enzymes, arginase, pyrimidine 5'-nucleotidase (P5N), and deoxypyrimidine 5'-nucleotidase (dP5N), were compared in 16 lead workers and 14 age matched controls as correlates of blood lead (PbB) and unextracted zinc protoporphyrin (EP) concentrations. Subjects with PbB of 0.9-2.5 microM (19-52 micrograms/dl) had 6.5 +/- 0.6 IU of P5N activity with uridine monophosphate (UMP) as substrate, significantly less (p less than 0.001) than the 12.0 +/- 0.7 IU activity of controls with PbB 0.3-0.6 microM (6-12 micrograms/dl). The mean activity of rbc dP5N with either deoxyuridine monophosphate (dUMP) or thymidine monophosphate as substrate, and of rbc arginase, did not differentiate the two groups. The correlation coefficients of ln PbB with the selected substrates for P5N and dP5N were: UMP, r = -0.75; dUMP, r = -0.61; TMP, r = -0.23. The correlation coefficient of ln PbB and arginase activity was -0.03. Rbc P5N (UMPase) is a significant correlate of PbB, equivalent to rbc protoporphyrin. HPLC assay of rbc UMPase activity is a sensitive and rapid assay that appears to meet criteria for a reliable clinical laboratory index of blood lead concentrations.

5'-Nucleotidase↗

PubMed1987

Hepatic and serum arginase and ornithine transcarbamylase activities of rats maintained on diets of different protein quality.

Groups of rats were fed diets containing 15% protein from arhar dal (Cajanus cajan), bengal gram dal (Cicer arietinum), urad dal (Phaseolus mungo) and also isolated proteins from casein, egg, soya bean, gluten and gelatin for a period of 10 days. Rats maintained on the casein diet had the highest liver arginase activity and those having egg the lowest. All the leguminous proteins gave similar levels of arginase activity, the values falling between the casein and egg groups. Serum arginase level was found to be low only in rats on egg and gluten diets. Liver ornithine transcarbamylase (OTC) activity was significantly higher when legumes provided the protein as compared with the diet containing egg. Serum OTC level was lowest in the egg and arhar dal groups. Though the levels of urea cycle enzymes were altered by the quality of dietary proteins, no simple relationship could be established between them.

Animals↗

PubMed1981

Role of sex steroid hormones in the normal and glucocorticosteroid hormone-induced evolution of carbamoylphosphate synthase (ammonia) and arginase activity in rat liver ontogenesis.

The effects of sex steroid hormones on the development changes of carbamoylphosphate synthase and arginase activity, and DNA content in rat liver were investigated. After birth, administration of estradiol causes an increase in carbamoylphosphate synthase and arginase activity at high dosages only. Progesterone strongly inhibits or even reverses these stimulatory effects of estradiol. Administration of progesterone alone had no effects in the 1st postnatal week, a stimulatory effect in the 2nd postnatal week, and slightly inhibitory effects on enzyme activities thereafter. Testosterone hardly affected enzyme activities in the 1st postnatal weeks and slightly decreased them from the 3rd postnatal week onwards. No differences in the response of either sex to these hormone treatments were observed. During the last 4 prenatal days and during the 1st postnatal week progesterone partially inhibited the prednisolone-induced enzyme accumulation and decrease in DNA content. Testosterone had such effects during the 1st 2 postnatal week. Comparison of these and previous experimental results with the developmental profiles of carbamoylphosphate synthase (ammonia) and arginase activity and DNA content on the one hand and with the developmental profile of steroid hormone levels on the other shows that only glucocorticosteroids influence enzyme activity and DNA content profiles, while progesterone and testosterone modulate the profiles by antagonizing the effects of glucocorticosteroids. No role for estrogens could be established.

Aging↗

PubMed1983

A comparative polyacrylamide gel electrophoretic study of arginase in vertebrate tissues.

The electrophoretic behaviour of arginase in the tissue extracts of rat, beef, lizard and frog was studied by bidirectional polyacrylamide gel electrophoresis. The enzyme from rat liver and submaxillary gland migrated to the cathode with the activity concentrated in a single peak. Arginase from beef liver emerged as a single peak of anodal migration with a significant shoulder in the sample gel. Frog liver and kidney enzymes also appeared as single peaks with a distinct anodal movement. The activity in mammalian kidney and lizard liver and kidney resolved into two peaks of anodal migration suggesting the presence of two isoenzymes of arginase in these tissues.

Animals↗

PubMed2005

Identification of macrophage arginase I as a new candidate gene of atherosclerosis resistance.

OBJECTIVE: Our laboratory has previously created 2 strains of rabbits with genetically determined high-atherosclerotic response (HAR) and low-atherosclerotic response (LAR). The aim of the present study was to identify new genes of atherosclerosis susceptibility in macrophages from the 2 strains. METHODS AND RESULTS: Suppression subtractive hybridization was used to screen for genes with higher expression in macrophages from LAR rabbits. We identified a cDNA fragment with high homology to human arginase I (AI; 91%) and subsequently cloned the full-length cDNA of the rabbit homologue. Quantitative RT-PCR revealed a significantly higher macrophage AI mRNA expression in LAR rabbits than in HAR rabbits (77428+/-10941 versus 34344+/-4538; P=0.002; copies/10(6) copies beta-actin), which also correlated with a significantly higher arginase enzyme activity. Northern blot analysis led to the identification of a size polymorphism of AI mRNA. This was because of a 413 bp C-repeat insertion in the 3' untranslated region. The shorter transcript variant was predominantly expressed in LAR rabbits and associated with significantly higher AI mRNA expression levels. Transfection experiments indicated decreased mRNA stability of the long AI variant. CONCLUSIONS: High expression of arginase I in macrophages may contribute to atherosclerosis resistance of LAR rabbits, possibly by conferring antiinflammatory effects in the vessel wall.

Animals↗

PubMed2006

Upregulation of arginase by H2O2 impairs endothelium-dependent nitric oxide-mediated dilation of coronary arterioles.

OBJECTIVE: Overproduction of reactive oxygen species such as hydrogen peroxide (H2O2) has been implicated in various cardiovascular diseases. However, mechanism(s) underlying coronary vascular dysfunction induced by H2O2 is unclear. We studied the effect of H2O2 on dilation of coronary arterioles to endothelium-dependent and endothelium-independent agonists. METHODS AND RESULTS: Porcine coronary arterioles were isolated and pressurized without flow for in vitro study. All vessels developed basal tone and dilated dose-dependently to activators of nitric oxide (NO) synthase (adenosine and ionomycin), cyclooxygenase (arachidonic acid), and cytochrome P450 monooxygenase (bradykinin). Intraluminal incubation of vessels with H2O2 (100 micromol/L, 60 minutes) did not alter basal tone but inhibited vasodilations to adenosine and ionomycin in a manner similar as that by NO synthase inhibitor L-NAME. H2O2 affected neither endothelium-dependent responses to arachidonic acid and bradykinin nor endothelium-independent dilation to sodium nitroprusside. The inhibited adenosine response was not reversed by removal of H2O2 but was restored by excess L-arginine. Inhibition of L-arginine consuming enzyme arginase by alpha-difluoromethylornithine or N(omega)-hydroxy-nor-L-arginine also restored vasodilation. Administering deferoxamine, an inhibitor of hydroxyl radical production, prevented the H2O2-induced impairment of vasodilation to adenosine. Western blot and reverse-transcription polymerase chain reaction results indicated that arginase I was upregulated after treating vessels with H2O2. CONCLUSIONS: H2O2 specifically impairs endothelium-dependent NO-mediated dilation of coronary microvessels by reducing L-arginine availability through upregulation of arginase. The formation of hydroxyl radicals from H2O2 may contribute to this process.

Animals↗

PubMed1982

Effects of glucocorticosteroids and glucagon on argininosuccinate synthetase, argninosuccinase, and arginase in fetal rat liver.

In the present study we examined the in vivo effects of glucocorticosteroids and glucagon on the developmental formation of the individual urea cycle enzymes argininosuccinate synthetase, argininosuccinase, and arginase during the late fetal period. In particular, addition of exogenous glucagon caused a rise in argininosuccinase and arginase activities in the livers of rat fetuses at term but not at earlier stages. Glucagon produced a rise in argininosuccinase activity earlier if fetuses were previously treated with cortisol. When fetuses were deprived of corticosteroid (hypophysectomy in utero), glucagon no longer promoted the argninosuccinase activity, indicating that adrenal glucocorticoids are required for normal enhancement of the enzyme activity by glucagon. Dibutyryl cAMP was still effective in hypophysectomized fetuses. Results obtained by injected combinations of inducers indicated that a glucocorticosteroid-glucagon interaction might be involved in the regulation of argininosuccinate synthetase and argininosuccinase. No synergistic action was found on arginase activity in vivo.

Animals↗

PubMed2006

Arginase alteration in the reproductive system of alloxan-diabetic dogs.

This study was conducted to evaluate possible alteration in the activity of arginase, an important enzyme of cell proliferation and vascular smooth muscle contraction regulator in diabetics, that may be correlated with low fertility in diabetic patients. In this investigation, 6 apparently healthy adult male dogs were selected and divided in two groups, diabetics and non-diabetics. Diabetes mellitus was induced in one group by intravenous (IV) injection of alloxan (100 mg/kg). Dogs with a fasting blood glucose (FBS) of more than 200 mg/dl were considered to be diabetic. Four weeks following induction of diabetes mellitus, the animals in both groups were anesthetized by an IV injection of sodium thiopental. Livers and whole reproductive systems, including the testes, penis, urethra, and prostate, were dissected. The epididymides, corpus cavernosum, corpus spongiosum, penile urethra, and vas deferens were also dissected and removed from the reproductive system. Arginase activity and total protein were measured by the urea and Lowry's methods respectively in above mentioned sections. Plasma testosterone was determined by the radioimmunoassay method. The results showed significantly (P<0.05) increased arginase specific activity (ASA) in the liver, epididymis, prostate, corpus cavernosum and corpus spongiosum of the diabetic dogs. In the reproductive system of the diabetic dog, the maximum and minimum ASA was seen in the corpus cavernosum and testes, respectively (105.12 +/- 8.76 vs. 25.0 +/- 0.55). No such variation was observed in the ASA of normal dogs (39.0 +/- 5.47 vs. 25.0 +/- 5.47). There was no significant difference in plasma testosterone level between the groups. In conclusion, diabetes increased the ASA in liver, prostate, epididymis, corpora cavernosa, and corpora spongiosum of the male dogs and may contribute to erectile dysfunction or low fertility in diabetics.

Alloxan↗

PubMed1979

Kinetic properties and regulation by L-ornithine of chicken liver arginase induced by insulin.

After injection of insulin into chickens, a new form of arginase with a 16-fold increase of activity appears in the liver. The new form has a different chromatographic behaviour on DEAE-cellulose. The low activity enzyme has a very high Km value (60mM), and is poorly inhibited by L-ornithine. The induced form of arginase is strongly inhibited by L-ornithine and has an allosteric behaviour which can be described by a Monod-Wyman-Changeux model. 1,4-Diaminobutane, spermine have practically no effect on either form of arginase.

Animals↗

PubMed1979

Arginase and free amino acids in hyperargininemia: leukocyte arginine as a diagnostic parameter for heterozygotes.

Arginase activity and free amino acids were measured in plasma, erythrocytes and leukocytes of patients with hyperargininemia and in controls. There is no arginase activity in the leukocytes and erythrocytes of homozygous patients; in heterozygotes it is normal to low. The activity is 50 to 100 times higher in leukocytes than in erythrocytes. In controls as well as in patients and heterozygotes, the amino acid concentrations are higher in leukocytes than in plasma and erythrocytes. In addition to the increased arginine in the three blood compartments (the result of an arginase deficiency), there is also an obvious decrease of aspartic acid in the erythrocytes of the patients. The arginine concentration in leukocytes of heterozygotes is as high as in homozygotes and can therefore be used as a diagnostic parameter for heterozygotes.

Amino Acid Metabolism, Inborn Errors↗

PubMed1996

Arginase activity determination. A marker of large bowel mucosa proliferation.

Arginase activity of the intestinal mucosa was tested as a proliferative marker in the adenoma-carcinoma sequence. The enzyme activity was determined by an end-point colorimetric method with L-arginine as substrate. Arginase activity was evaluated in 430 biopsy samples of large bowel mucosa, polyps and cancer tissue. The activities (U/g protein, mean +/- SE; n) were: normal mucosa 83.2 +/- 7.3; 25, adenomas 199.4 +/- 19.1; 40, carcinomas 1269.7 +/- 174.9; 40, inflammatory bowel disease 1210.7 +/- 247.1; 34. The arginase activity differs significantly in the adenoma-carcinoma sequence according to the Duncan's test (p < 0.05).

Arginase↗