Disease relevance of Arg1

• Reduction of arginase I in BDL livers may be responsible for the lowering of arginine levels in the plasma, while induction of arginase II could be important in regulating NO synthesis as well as other important mechanisms involved in liver cirrhosis [1].
• These findings suggest that decreased arginase expression in the kidney may be at least partially responsible for the salt-sensitive hypertension in SS rats [2].
• Functional consequences of the G235R mutation in liver arginase leading to hyperargininemia [3].
• The regulation of expression of the arginine-recycling enzymes and arginase isoforms in association with inducible nitric oxide synthase (iNOS) in the eye of endotoxin-induced uveitis (EIU) rats is investigated [4].
• The expression of arginase in normal lung and after sepsis, and its potential relationships with iNOS, however, are not known [5].

Psychiatry related information on Arg1

• Recent studies have demonstrated that arginase plays important roles in pathologies such as asthma or erectile dysfunctions [6].

High impact information on Arg1

• In other tissues that lack a complete urea cycle, arginase regulates cellular arginine and ornithine concentrations for biosynthetic reactions, including nitric oxide synthesis: in the macrophage, arginase activity is reciprocally coordinated with that of NO synthase to modulate NO-dependent cytotoxicity [7].
• Structure of a unique binuclear manganese cluster in arginase [7].
• The 2.1 angstrom-resolution crystal structure of trimeric rat liver arginase reveals that this unique metal cluster resides at the bottom of an active-site cleft that is 15 angstroms deep [7].
• The marked effects of L-arginine availability on macrophage functions, together with the knowledge that these cells modify the extracellular arginine concentration in sites of inflammation through arginase, provide evidence for an autoregulatory mechanism of macrophage activation [8].
• We show that a consequence of elevated cAMP is the synthesis of polyamines, resulting from an up-regulation of Arginase I, a key enzyme in their synthesis [9].

Chemical compound and disease context of Arg1

• To examine the effect of urea, the product of arginase reaction, on the development of hypertension, SS rats were given a 4% NaCl diet containing 5% kaolin or 5% urea [2].
• Depletion of the culture medium of arginine by arginase or arginine-free growth medium completely attenuates N-methyl-D-aspartate toxicity [10].
• The pluripotency of recombinant arginase was demonstrated by its ability to inhibit apoptosis in multiple paradigms including rat cortical neurons induced to die by glutathione depletion and oxidative stress, by 100 nM staurosporine treatment, or by Sindbis virus infection [11].
• The dimanganese (II,II) catalase from Thermus thermophilus, MnCat(II,II), arginase from rat liver, Arg(II,II), and several dimanganese(II,II) compounds, LMn2XY2, which are functional catalase mimics, all possess a pair of coupled Mn(II) ions in their catalytic sites [12].
• Nitrites and nitrates in supernatants of isolated alveolar macrophages decreased after peritonitis compared with healthy rats, and an inhibitory experiment suggested arginase overactivity in alveolar macrophages bypassing the NO substrate [13].

Biological context of Arg1

• Arginase catalyzes the hydrolysis of arginine to urea and ornithine [2].
• Comparison of the deduced amino acid sequence of the rat liver arginase with that of the yeast enzyme revealed a 40% homology [14].
• The nucleotide sequence of rat liver arginase cDNA, which was isolated previously (Kawamoto, S., Amaya, Y., Oda, T., Kuzumi, T., Saheki, T., Kimura, S., and Mori, M. (1986) Biochem. Biophys. Res. Commun. 136, 955-961) was determined [14].
• The promoter region of the rat arginase gene was investigated with an in vitro transcription system using nuclear extracts prepared from rat tissues [15].
• The G235R (patient) and G235A (control) arginase mutants of rat liver arginase have been generated to probe the effects of these point mutations on the structure and function of hepatic type I arginase [3].

Anatomical context of Arg1

• Age-related changes in nitric oxide synthase and arginase in the rat prefrontal cortex [16].
• The present study investigates for the first time the regional variations and age-related changes in both NOS and arginase in sub-regions of the hippocampus [17].
• In young adult rats, although the total NOS activity was not significantly different across the hippocampal CA1, CA2/3 and the dentate gyrus (DG) sub-regions, the total arginase activity showed a clear regional variation with the highest level in DG [17].
• Thus, arginase I appears to have an important role in down-regulating nitric oxide synthesis in murine macrophages by decreasing the availability of arginine, and the induction of arginase I is mediated by C/EBPbeta [18].
• Coinduction of nitric-oxide synthase and arginase I in cultured rat peritoneal macrophages and rat tissues in vivo by lipopolysaccharide [18].

Associations of Arg1 with chemical compounds

• L-arginine can be metabolised by nitric oxide synthase (NOS) with the formation of L-citrulline and nitric oxide (NO), or arginase with the production of L-ornithine and urea [17].
• Nitric oxide is synthesized by nitric-oxide synthase from arginine, a common substrate of arginase [18].
• Arginase is a thermostable (Tm = 75 degrees C) binuclear manganese metalloenzyme which hydrolyzes l-arginine to form l-ornithine and urea [19].
• Substance P or its antagonist [(Arg1, D-Trp7,9, Leu11)-substance P: spantide] was injected into the subarachnoid space via polyethylene tubing [20].
• Proteinase K digestion of GPRP produced a homogeneous glycopeptide with an average chemical composition as follows (residues per mol): Pro4, Glx3, Asx2, Gly1, His1, Thr1, Arg1, GlcNAc5, GalNac1, Man3, Gal2-3, and Fuc1 [21].

Regulatory relationships of Arg1

• IL-4 and IL-13 upregulate arginase I expression by cAMP and JAK/STAT6 pathways in vascular smooth muscle cells [22].
• This is the first evidence that TGF-beta up-regulates arginase activity in macrophages and, hence, limits macrophage-dependent cytostasis [23].
• In addition, lyso-PC stimulated intracellular cationic amino acid metabolism by inducing ornithine decarboxylase activity and mRNA expression and also by inducing arginase activity in vascular SMC [24].
• Arginase activity could be induced by dexamethasone in hepatocytes isolated from 16.5-d-old fetuses although cells were competent to respond to glucagon only at the stage of 18.5 d [25].

Other interactions of Arg1

• There was no regional variation in arginase I or arginase II protein expression across the sub-regions of the hippocampus [17].
• TGF-beta and IL-4 significantly increased arginase activity and protein expression whereas lipopolysaccharide and wound fluid did not affect it [26].
• Moreover, arginase inhibition restores endothelial NOS signaling and l-arginine responsiveness in old rat aorta [27].
• Arginase I mRNA and protein was not affected by IFN-gamma, but increased by LPS and this effect was prevented by dexamethasone [28].
• PURPOSE: Production of NO may be regulated by argininosuccinate synthetase and argininosuccinate lyase which recycle citrulline to arginine, and by arginase which hydrolyzes arginine to urea and ornithine [29].

Analytical, diagnostic and therapeutic context of Arg1

• Competitive polymerase chain reaction was performed to assay the expression of messenger RNA of arginase I and II [1].
• Arginase activity was measured by newly formed urea (nmol/min/mg protein) and protein expression was detected by Western blotting using specific antibodies for type I (AI) and type II (AII) [26].
• Immunohistochemistry, immunoblotting, and enzyme assay confirmed a significant knockdown of Arg I protein and arginase activity in AS but not S or C rings [27].
• We demonstrate the existence of at least 6 HPLC components, distinguishable from bradykinin, bradykinin homologues having Lys before Arg1 of bradykinin and T-kinin (Ile-Ser-bradykinin) on the basis of their chromatographic properties [30].
• Effects of depletion of CD4+ cells, neutralization of interleukin (IL)-4 or application of arginase inhibitors N(omega)-hydroxy-L-arginine (L-NOHA) and L-valine on production of NO in rejected xenografts were evaluated [31].

References