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At least 19 recordsLinked to original sources
PubMed2004

Purification and characterization of Helicobacter pylori arginase, RocF: unique features among the arginase superfamily.

The urea cycle enzyme arginase (EC 3.5.3.1) hydrolyzes l-arginine to l-ornithine and urea. Mammalian arginases require manganese, have a highly alkaline pH optimum and are resistant to reducing agents. The gastric human pathogen, Helicobacter pylori, also has a complete urea cycle and contains the rocF gene encoding arginase (RocF), which is involved in the pathogenesis of H. pylori infection. Its arginase is specifically involved in acid resistance and inhibits host nitric oxide production. The rocF gene was found to confer arginase activity to Escherichia coli; disruption of plasmid-borne rocF abolished arginase activity. A translationally fused His(6)-RocF was purified from E. coli under nondenaturing conditions and had catalytic activity. Remarkably, the purified enzyme had an acidic pH optimum of 6.1. Both purified arginase and arginase-containing H. pylori extracts exhibited optimal catalytic activity with cobalt as a metal cofactor; manganese and nickel were significantly less efficient in catalyzing the hydrolysis of arginine. Viable H. pylori or E. coli containing rocF had significantly more arginase activity when grown with cobalt in the culture medium than when grown with manganese or no divalent metal. His(6)-RocF arginase activity was inhibited by low concentrations of reducing agents. Antibodies raised to purified His(6)-RocF reacted with both H. pylori and E. coli extracts containing arginase, but not with extracts from rocF mutants of H. pylori or E. coli lacking the rocF gene. The results indicate that H. pylori RocF is necessary and sufficient for arginase activity and has unparalleled features among the arginase superfamily, which may reflect the unique gastric ecological niche of this organism.

Arginase↗
PubMed1986

Cloning of rat liver arginase cDNA and elucidation of regulation of arginase gene expression in H4 rat hepatoma cells.

In order to study the regulation of expression of the two arginase genes in mammalian tissues, we undertook to clone cDNA specific for rat liver arginase. mRNA was isolated from rat liver polysomes enriched for the arginase message by immunopurification and was used to produce an 800-member cDNA library carried in pBR322. Four arginase clones were identified by hybrid selection, and one was used to find two others following colony hybridization. Clonal identity was verified by its enrichment in the cDNA made from immunopurified mRNA; by hybrid selection, immunoprecipitation, and competition by purified arginase; hybridization on Northern analysis with liver-derived RNA (high in arginase) and its absence with mRNA from tissues low in arginase; and independent identification by hybrid selection and colony hybridization. Northern analysis of mRNA from H4-II-E-C3 (H4) rat hepatoma cells in which arginase activity was induced by hydrocortisone demonstrated equal, eightfold augmentation of both arginase activity and arginase mRNA levels. Southern blot analysis of DNA from these cells indicated that no change in arrangement or copy number accompanied induction. Southern analysis also suggested that the gene for rat liver arginase is present in a single copy, without pseudogenes, and that a high degree of homology exists between it and its mouse counterpart.

Animals↗
PubMed1996

Molecular cloning of cDNA for nonhepatic mitochondrial arginase (arginase II) and comparison of its induction with nitric oxide synthase in a murine macrophage-like cell line.

Arginase exists in two isoforms. Liver-type arginase (arginase I) is expressed almost exclusively in the liver and catalyzes the last step of urea synthesis, whereas the nonhepatic type (arginase II) is expressed in extrahepatic tissues. Arginase II has been proposed to play a role in down-regulation of nitric oxide synthesis. A cDNA for human arginase II was isolated. A polypeptide of 354 amino acid residues including the putative NH2-terminal presequence for mitochondrial import was predicted. It was 59% identical with arginase I. The arginase II precursor synthesized in vitro was imported into isolated mitochondria and proteolytically processed. mRNA for human arginase II was present in the kidney and other tissues, but was not detected in the liver. Arginase II mRNA was coinduced with nitric oxide synthase mRNA in murine macrophage-like RAW 264.7 cells by lipopolysaccharide. This induction was enhanced by dexamethasone and dibutyryl cAMP, and was prevented by interferon-gamma. Possible roles of arginase II in NO synthesis are discussed.

Amino Acid Sequence↗
PubMed1986

Studies on L-arginase in developing rat small intestine, brain, and kidney. I. Ontogenic evolution of arginase isoenzymes.

The adult patterns of arginase isoenzymes in rat intestine, kidney, and brain are nearly identical and consist of two forms, cationic A1 and anionic A4. In this paper, the organ-specific maturation of the enzyme equipment in these tissues is reported. The activity of arginase in all tissues studied could be detected on the 13th to 16th days of gestation. In fetal intestine and kidney the arginase activity is low, and persists up to the weaning time when the rapid, 10-fold rise of the enzyme activity occurs. However, the adult pattern of arginase isoenzymes in these tissues is accomplished in different ways. In the intestine, arginase A1 appears in fetal life and is the only form of the enzyme till the 19th to 21st days of postnatal life when the second form of arginase, A4, appears and rapidly accumulates, being exclusively responsible for the rise of the total enzyme activity at the time of weaning. In kidney, arginase A1 alone is present in the early fetal period. Arginase A4 appears 3-4 days before birth and its activity persists unchanged within the first 2 weeks of postnatal life. The intensive rise in total specific activity of kidney arginase at weaning is due to the accumulation of preexisting arginase A4. In brain, the adult pattern of arginase isoenzymes is achieved earlier than in other tissues. Both forms, A1 and A4, occur on Days 13-14 of gestation.

Aging↗
PubMed1993

Evidence for the pre-synthesized state of secreted macrophage arginase: arginase activity cannot be modified in short-term cultures.

The arginase produced by peritoneal macrophages is not synthesized de novo in short-term (3 h) cultures after harvesting the cells. In long-term cultures the arginase synthesis is restored. In contrast to arginase lysozyme is continuously synthesized in short-term cultures. These statements were proved by the following experimental results: 1. Protein synthesis inhibitor and lysosomotropic agents did not alter the arginase level. 2. Arginine and its analogue, canavanine and ornithine were not able to change the arginase activity. 3. The product of an alternative metabolic pathway of arginine, sodium nitrite, did not affect arginase activity. 4. Effectors influencing the synthesis of cyclic nucleotides (cAMP, cGMP), indomethacin, sodium nitroprusside and an analogue of cAMP had no effect on the arginase activity. 5. Arginase activity could not be significantly modified either by an in vitro Micrococcus luteus treatment or by changing the adherence period of peritoneal exudate cells. 6. When arginase was produced in murine peritoneal macrophages at various periods with medium change, the total arginase released into the media from murine and rat macrophages did not exceed the original intracellular arginase content of the adhered cells during the first 6 hours.

Animals↗
PubMed2006

Overexpression of arginase in the aged mouse penis impairs erectile function and decreases eNOS activity: influence of in vivo gene therapy of anti-arginase.

Since both increased nitric oxide (NO) synthase (NOS) abundance and diminished NO signaling have been reported in the aging penis, the role of NO in the adaptations of aging remains controversial. Here we tested the hypothesis that arginase, an enzyme that competes with NOS for the substrate l-arginine, contributes to erectile dysfunction with advanced age in the B6/129 mouse strain. Arginase protein abundance, mRNA expression, and enzyme activity were elevated in aged compared with young penile endothelial cells. In addition, endothelial NOS (NOS3) protein abundance was greater in aged versus young penile endothelial cells, whereas NOS activity and cGMP levels were reduced. Calcium-dependent l-arginine-to-l-citrulline conversion and cGMP formation increased significantly in aged mouse penes in the presence of the arginase inhibitor 2(S)-amino-6-boronohexanoic acid (ABH). However, there was no effect on l-arginine-to-l-citrulline conversion or cGMP accumulation in the endothelium from young mouse penes. To assess the functional role of arginase in the inhibition of NOS pathway responsiveness in the penis, we evaluated the effects of ABH and an adeno-associated virus encoding an antisense sequence to arginase I (AAVanti-arginase) on erectile function in vivo. ABH and AAVanti-arginase enhanced endothelium-dependent erectile responses in the aged mice without altering endothelium-independent responses. Paralleling our in vitro observations, ABH or AAVanti-arginase did not affect vascular responses in the young mice. Inhibition of the arginase pathway improves endothelial function in the aging penile circulation, suggesting that the arginase pathway may be exploited to improve erectile dysfunction associated with aging.

Aging↗
PubMed1980

Properties of arginase from liver of Macaca fascicularis; comparison of normals with red blood cell arginase deficient monkeys.

Deficiency of arginase (E.C. 3.5.3.1), the fifth enzyme of the urea cycle, was found in the red blood cells (RBCs) of Macaca fascicularis monkeys (less than 0.2 micromol arginine cleaved/g Hb/min; normal equals 49.2). Liver biopsies were obtained from two of these monkeys and from one monkey with normal levels of RBC arginase activity. Arginase from both groups of animals required Mn2+ for maximal enzyme activity and demonstrated a pH optimum of 10.2 in vitro. The activity of arginase in the livers of all three monkeys was 1.1 millimol arginine cleaved per g protein per min. The apparent Km for arginine of arginase in the livers of the RBC-deficient monkeys was 7.4 and 5.9 mM and in the normal monkey was 6.9 mM. Similar patterns of heat denaturation was seen at 69 C without Mn2+ present and 79 C in the presence of 20mM Mn2+. No difference in mobility on either RBC-deficient or normal monkeys was found. In addition, liver arginase from all three monkeys reacted similarly with anti-human liver arginase antibody. Liver arginases in RBC-deficient and normal monkeys were identical by ten criteria. These studies do not distinguish among several hypotheses for the genetic determination of arginase in different organs of this species and of man.

Amino Acid Metabolism, Inborn Errors↗
PubMed1984

Hyperargininemia: the rat as a model for the human disease and the comparative response to enzyme replacement therapy with free arginase and arginase-loaded erythrocytes in vivo.

Rat erythrocytes lack arginase as do the erythrocytes of human homozygote patients with hyperargininemia due to arginase deficiency. The rat has physiological liver arginase activity and plasma arginine and ornithine levels between the homozygotes and the heterozygotes with hyperargininemia. In rats, one injection of free arginase induces a transient exogenous arginase effect which is abolished after 24 hr. One injection of isoionic arginase-loaded erythrocytes provokes an exogenous arginase effect in physiological "hyperargininemic" rats and pathological "hyperargininemic"-made rats for at least 8 and 5 days respectively. The very transient response in vivo to exogenous free arginase can be considerably prolonged by entrapment of the arginase in isoionic prepared erythrocytes.

Amino Acid Metabolism, Inborn Errors↗
PubMed1983

Immunologic studies of arginase in tissues of normal human adult and arginase-deficient patients.

Rabbit antibody to human liver arginase was used to examine the immunologic characteristics of arginase in red blood cells (RBC), liver, kidney, brain, and gastrointestinal tract from normal adults and from patients with hyperargininemia. Greater than 90% of the arginase in RBC and liver was precipitated by this antibody whereas only 50% of the arginase in kidney, brain, and gastrointestinal tract reacted with it. Two siblings and a third patient with hyperargininemia were found to have immunoreactive arginase protein in their RBC that was enzymatically inactive. The amount of arginase protein approximated that found in RBC from normal individuals. A kidney biopsy obtained from one of the patients with hyperargininemia had arginase activity 4-5-fold greater than that found in normal kidney biopsy material. Double immunodiffusion and precipitation-inhibition studies demonstrated two types of arginase protein in this patient's kidney: one enzymatically inactive and precipitated by the antibody, and one enzymatically active but not precipitated by the antibody. These data, in conjunction with biochemical data reported previously demonstrate that there are two gene loci determining arginase in man.

Amino Acid Metabolism, Inborn Errors↗
PubMed1986

Isolation of human liver arginase cDNA and demonstration of nonhomology between the two human arginase genes.

A human liver cDNA library was screened by colony hybridization with a rat liver arginase cDNA. The number of positive clones detected was in agreement with the estimated abundance of arginase message in liver, and the identities of several of these clones were verified by hybrid-select translation, immunoprecipitation, and competition by purified arginase. The largest of these human liver arginase cDNAs was then used to detect arginase message on northern blots at levels consistent with the activities of liver arginase in the tissues and cells studied. The absence of a hybridization signal with mRNA from a cell line expressing only human kidney arginase demonstrated the lack of homology between the two human arginase genes and indicated considerable evolutionary divergence between these two loci.

Arginase↗
PubMed2001

Generation of a mouse model for arginase II deficiency by targeted disruption of the arginase II gene.

Mammals express two isoforms of arginase, designated types I and II. Arginase I is a component of the urea cycle, and inherited defects in arginase I have deleterious consequences in humans. In contrast, the physiologic role of arginase II has not been defined, and no deficiencies in arginase II have been identified in humans. Mice with a disruption in the arginase II gene were created to investigate the role of this enzyme. Homozygous arginase II-deficient mice were viable and apparently indistinguishable from wild-type mice, except for an elevated plasma arginine level which indicates that arginase II plays an important role in arginine homeostasis.

Amino Acids↗
PubMed1987

The effects of arginase on neoplasm. I. The role of arginase in the immunosuppressive effects of extract from gastric cancer.

Arginase, a potent immune inhibitor, is studied in gastric cancer for its possible role in immunosuppression. Aqueous extracts (n = 12) from gastric cancer tissue inhibited PHA-induced lymphocyte proliferation more than those from normal gastric mucosal tissues (p less than 0.05). The inhibition was not due to cytotoxic effect of the extracts. Gastric arginase was isolated from gastric extracts by an affinity column conjugated with an anti-arginase antibody. The arginase from both normal and cancer gastric tissues strongly inhibited lymphocyte proliferation. By using enzyme-immunoassay, the arginase contents in cancer tissues were determined and showed 3 times as much as that in normal gastric mucosal tissues (n = 14) (p less than 0.005). The increased arginase content in cancer tissue was further confirmed by immunohistochemistry study. Arginase exists abundantly amounts in the cytoplasm of cancer cells, much more than that of normal cells (n = 30). It is conceivable that the depressed cellular immunity in gastric cancer patients might be partly due to the abundant amount of arginase in cancer cells.

Arginase↗
PubMed1995

Arginase release following liver reperfusion. Evidence of hemodynamic action of arginase infusions.

Immediately after hepatic reperfusion in human orthotopic liver transplantation, high amounts of arginase are released from the graft, thereby influencing nitric oxide metabolism. This metabolic alteration may be one component of the ischemia-reperfusion syndrome in OLT with its hemodynamic disturbances (e.g., systemic hypotension, pulmonary hypertension). The aim of this study was to compare hemodynamic and metabolic changes following OLT in the pigs with those obtained under arginase infusions in catheterized, anesthetized pigs. Following liver revascularization in the pigs, plasma arginase concentrations increased from 48 +/- 19 IU/L to 2613 +/- 944 IU/L, resulting in a drop in plasma levels of L-arginine (-87%) and in a drop in nitrite (-82%) and nitrate (-53%) concentrations. Of the measured organ-specific hemodynamic alterations, the mean pulmonary arterial pressure increased from 17 +/- 2 mmHg to 30 +/- 5 mmHg, whereas the flow/pressure index of the portal vein decreased about 60%. A primed continuous infusion of arginase (25,000 IU) increased plasma arginase levels to a maximum of 3,690 +/- 962 IU and evoked a decrease of L-arginine, but did not alter plasma nitrite or nitrate levels. The administration of arginase in healthy pigs did not influence cardiac output, mean arterial pressure, heart rate, or total peripheral resistance, but led to an increase of mean pulmonary arterial pressure from 19 +/- 3 to 48 +/- 5 mmHg and to a reduction of arterial hepatic blood flow from 229 +/- 65 ml/min to 154 +/- 41 ml/min. From this we conclude that high levels of liver arginase cause hemodynamic alterations in the lung and the liver. We hypothesize that the pulmonary hypertension and the reduced hepatic blood flow found during the immediate reperfusion period after OLT are possibly related to the increased arginase release due to the hepatic damage of the graft.

Animals↗
PubMed1985

Purification, affinity to anti-human arginase immunoglobulin-Sepharose 4B and subunit molecular weights of mammalian arginases.

The affinities of anti-human liver arginase antibodies raised in rabbits to liver arginases from man, bovine, pig, dog, guinea pig, rat and mouse were investigated by Scatchard analysis of the binding of the arginases from crude liver extracts to Sepharose-bound immunoglobulins. All arginases bound with good affinity, but the binding capacities of the immunosorbent for the enzymes from various species decreased with decreasing phylogenetic relationship of the species. Arginase from murine peritoneal macrophages did not bind to the immunosorbent at all. A simple two-step purification method for the liver arginases of all species mentioned above is given. All arginases were purified to electrophoretical homogeneity. The molecular weights of their subunits were estimated.

Animals↗
PubMed1998

The human arginases and arginase deficiency.

Arginase is the final enzyme in the urea cycle. Its deficiency is the least frequently described disorder of this cycle. It results primarily in elevated blood arginine, and less frequently in either persistent or acute elevations in blood ammonia. This appears to be due to a second arginase locus, expressed primarily in the kidney, which can be recruited to compensate, in part, for the deficiency of liver arginase. The liver arginase gene structure permitted study of the molecular pathology of patients with the disorder and the results of these studies and the inferences about the protein structure are presented. The conserved regions among all arginases allowed the cloning of AII, the second arginase isoform. It has been localized to the mitochondrion and is thought to be involved in ornithine biosynthesis. It shares the major conserved protein sequences, and structural features of liver arginase gene are also conserved. When AI and AII from various species are compared, it appears that the two diverged some time prior to the evolution of amphibians. The evidence for the role of AII in nitric oxide and polyamine metabolism is presented and this appears consonant with the data on the tissue distribution.

Amino Acid Metabolism, Inborn Errors↗
PubMed2004

[Arginase as a marker of cancerogenesis. III. Comparison of arginase activity with CEA and Ca 19-9 in liver metastases of colorectal cancer].

Preoperative activity of arginase was determined in blood serum of 86 patients with colorectal liver metastases and compared with the level of CEA and Ca 19-9. Arginase activity was elevated in 94% patients, whereas the levels of CEA and CA 19-9 were higher in 63% and 45% patients, respectively. The number of not detected by each marker cases (false negative) was much lower in arginase determination (only 6%) than in CEA (37s%), and Ca 19-9 (55%). Sensitivity and specificity of arginase test was much higher than these of CEA and Ca 19-9. The combination of CEA or Ca 19-9 with arginase determination improved the sensitivity of either test, but the combined parameters were still lower than these for arginase itself. Obtained results indicate that arginase test demonstrate higher clinical value in the early diagnosis of colorectal liver metastases than CEA and Ca 19-9.

Adult↗