Comparative properties of arginases

Jenkinson, Christopher P.; Grody, Wayne W.; Cederbaum, Stephen D.

doi:10.1016/0305-0491(95)02138-8

Cited by 564 publications

(483 citation statements)

References 194 publications

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“…There are two distinct isoforms of mammalian arginase (arginase I and arginase II) that are encoded by different genes and differ in molecular and immunological properties, tissue distribution, subcellular location, and regulation of expression (12,13). Arginase I is highly expressed in the liver of higher animals to detoxify ammonia.…”

Section: Discussionmentioning

confidence: 99%

Elevated arginase I expression in rat aortic smooth muscle cells increases cell proliferation

Liu

Wu²,

Morris³

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

139

109

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Arginase, which exists as the isoforms arginase I and II, catalyzes the hydrolysis of arginine to ornithine and urea. Ornithine is the principal precursor for production of polyamines, which are required for cell proliferation. Rat aortic smooth muscle cells (RASMC) contain constitutive arginase I, and arginase inhibitors cause inhibition of cell proliferation. The objective of this study was to determine whether the elevated expression of arginase I in RASMC causes increased cell proliferation. RASMC were stably transfected with either rat arginase I cDNA or a ␤-galactosidase control expression plasmid. Western blots and arginase enzymatic assays revealed high-level expression of cytosolic arginase I in arginase I-transfected RASMC. Moreover, this observation was associated with the increased production of urea and polyamines and higher rates of RASMC proliferation. The two selective inhibitors of arginase, N G -hydroxy-L-arginine and S-(2-boronoethyl)-Lcysteine, inhibited arginase and decreased the production of urea and polyamines in arginase I-transfected RASMC, all of which were associated with the inhibition of cell proliferation. This study demonstrates that elevated arginase I expression increases RASMC proliferation by mechanisms involving increased production of polyamines. These observations suggest that arginase I plays a potentially important role in controlling RASMC proliferation.nitric oxide ͉ vascular smooth muscle growth ͉ polyamines ͉ atherosclerosis

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Section: Discussionmentioning

confidence: 99%

Elevated arginase I expression in rat aortic smooth muscle cells increases cell proliferation

Liu

Wu²,

Morris³

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

139

109

View full text Add to dashboard Cite

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“…The highest activity of arginase is found in liver that contains arginase I. The liver is the only organ containing all the enzymes of the urea cycle, which underscores its important role in ammonia detoxification occurring through this cycle (17). Significant amounts of arginase I and II have been detected in a number of extrahepatic tissues that lack a complete urea cycle, suggesting other functions of arginase in addition to its role in ureagenesis in the liver.…”

mentioning

confidence: 97%

“…Significant amounts of arginase I and II have been detected in a number of extrahepatic tissues that lack a complete urea cycle, suggesting other functions of arginase in addition to its role in ureagenesis in the liver. These functions include the biosynthesis of ornithine as a precursor of polyamines, biosynthesis of glutamate (precursor of ␥-aminobutyric acid) and proline, modulation of NO synthesis, regulation of inflammatory and immunologic responses and wound healing, and regulation of airway smooth muscle relaxation (17).…”

mentioning

confidence: 99%

Endothelial dysfunction in rat adjuvant‐induced arthritis: Up‐regulation of the vascular arginase pathway

Prati¹,

Berthelot²,

Wendling³

et al. 2011

Arthritis & Rheumatism

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Objective. To investigate whether arginase pathway abnormalities occur in vessels from rats with adjuvant-induced arthritis (AIA), and to determine whether the up-regulation of arginase, which reciprocally regulates nitric oxide synthase (NOS) by competing for the same substrate, L-arginine, contributes to endothelial dysfunction in AIA.Methods. We performed vascular reactivity experiments on thoracic aortic rings from AIA rats and control rats, and we investigated the response of rings to norepinephrine (NE), sodium nitroprusside (SNP), and acetylcholine (ACh). ACh-induced relaxation was evaluated in the presence (or not in the presence) of the NOS inhibitor N G -nitro-L-arginine methyl ester (L-NAME), the arginase inhibitor N -hydroxy-nor-Larginine (nor-NOHA), or both. Aortic arginase activity was measured using a spectrophotometric method, and the expression of arginase and endothelial NOS (eNOS) was evaluated by Western blotting.Results. ACh-induced vasodilation was significantly impaired in AIA rats, while the responses to NE and to SNP did not differ from those in control rats. L-NAME reduced ACh-induced vasodilation to a lesser extent in AIA rats than in control rats. Incubation of aortic rings with nor-NOHA enhanced the vascular response to ACh in AIA rats and reversed the effects of L-NAME. Compared with control rats, AIA rats exhibited increased vascular expression of arginase II (by 22%) (P < 0.05) as well as increased arginase activity (by 49%) (P < 0.05), whereas eNOS expression was unchanged. Finally, arginase activity and expression correlated positively with arthritis severity.Conclusion. Our results are consistent with the notion that arginase up-regulation plays a role in AIAassociated endothelial dysfunction. They suggest that arginase might be an attractive new target for treating endothelial dysfunction in arthritis.

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“…We considered the possibility that, although the enzyme is reported to require free arginine (20), HNP-1 could be a substrate for bovine liver arginase. HNP-1 (1.4 nmol), mono-ADP-ribosylated-HNP-1 (1 nmol), ADP-ribosylarginine (18 M), and arginine (5 mM) were incubated with manganese-activated arginase (0.7 units) at pH 9.5 (in 200 L, 37°C, 10 min), conditions used for arginase hydrolysis of arginine to ornithine (21).…”

Section: Nmol) (D and E)mentioning

confidence: 99%

ADP-ribosylation of human defensin HNP-1 results in the replacement of the modified arginine with the noncoded amino acid ornithine

Stevens

Levine

Gochuico

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Defensins (e.g., human neutrophil peptides, or HNPs) contribute to innate immunity through diverse actions, including microbial killing; high concentrations are present in the lung in response to inflammation. Arginines are critical for HNP activity, which is decreased by their replacement with ornithine. ADP-ribosyltransferases (ARTs) catalyze transfer of ADP-ribose from NAD to an acceptor arginine in a protein substrate, whereas ADP-ribosylarginine hydrolases release ADPribose. ART1 on the surface of airway epithelial cells ADP-ribosylated HNP-1 specifically on arginines 14 and 24, with ADP-ribosylation altering biological activity. Di-and mono-ADP-ribosylated HNP-1 were isolated from bronchoalveolar lavage fluid (BALF) of patients with asthma and idiopathic pulmonary fibrosis (IPF), suggesting a role for ADP-ribosylation in disease. In the present study, we observed that ART1-catalyzed ADP-ribosylation of HNP-1 in vitro generated a product with ADP-ribose on arginine 24, and ornithine replacing arginine at position 14. We hypothesized that ADP-ribosylarginine is susceptible to a nonenzymatic hydrolytic reaction yielding ornithine. On incubation of di-or mono-ADP-ribosyl-HNP-1 at 37°C, ADP-ribosylarginine was partially replaced by ornithine, whereas ornithine was not detected by amino acid analysis and mass spectrometry of unmodified HNP-1 incubated under the same conditions. Further, ornithine was produced from the model compound, ADPribosylarginine. BALF from an IPF patient contained ADP-ribosyl-HNPornithine as well as mono-and di-ADP-ribosylated HNP-1, consistent with in vivo conversion of arginine to ornithine. Targeted ADPribosylation of specific arginines by transferases, resulting in their replacement with ornithine, is an alternative pathway for regulation of protein function through posttranslational modification.posttranslational modification ͉ NAD ͉ bacterial toxins N eutrophils, a critical component of the innate immune system, are recruited to airways in response to inflammation or infection (1). Neutrophil defensins [human neutrophil peptides (HNPs) 1-3], stored in azurophilic granules, are small cationic peptides whose main function is to defend the lung against pathogenic microorganisms (2). High levels of defensins have been found in patients with inflammatory lung diseases, such as idiopathic pulmonary fibrosis (IPF) (3) and cystic fibrosis (4). In addition to antimicrobial activities and other diverse functions (5), defensins interact with airway epithelial cells, increasing proliferation and stimulating wound repair (6). HNP1-3 are arginine rich and differ in sequence by one amino acid. The salt bridge formed by Arg 5 -Glu 13 and three disulfide bridges are conserved, but not required, for antibacterial activity in vitro (7,8). The arginines in HNP-1 are critical for maintaining activity (9). In addition, the low number of arginines in HD6 (human defensin 6 expressed in Paneth cells) may be responsible for its lack of antibacterial activity (10).Mono-ADP-ribosylation is a posttranslational ...

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Comparative properties of arginases

Cited by 564 publications

References 194 publications

Elevated arginase I expression in rat aortic smooth muscle cells increases cell proliferation

Elevated arginase I expression in rat aortic smooth muscle cells increases cell proliferation

Endothelial dysfunction in rat adjuvant‐induced arthritis: Up‐regulation of the vascular arginase pathway

ADP-ribosylation of human defensin HNP-1 results in the replacement of the modified arginine with the noncoded amino acid ornithine

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