Disease relevance of Arg2

• The AI knockout animals die by 14 days of age from hyperammonemia, while the AII knockout has no obvious phenotype [1].
• Peritonitis increased messenger RNA levels of arginase I and arginase II in controls and SAD mice but with a greater increase in arginase I in SAD than in control mice [2].
• To determine whether these two HDL populations have different effects on atherogenesis, human apoA-I (AI) and human apoA-I and apoA-II (AI/AII) transgenic mice were produced in an atherosclerosis-susceptible strain [3].
• We also demonstrate that arginase II expression is up-regulated in both murine and human H. pylori gastritis tissues, indicating the likely in vivo relevance of our findings [4].
• Helicobacter pylori induces macrophage apoptosis by activation of arginase II [4].

Psychiatry related information on Arg2

• Since angiotensin II (AII) is a powerful elicitor of drinking behavior, we investigated the influence of the angiotensin converting enzyme inhibitor, captopril, on the amount of water consumed by the STR/N mouse [5].
• Male spiny mice (Acomys cahirinus) were challenged with several putative dipsogenic stimulus conditions: hypertonic sodium chloride (NaCl), 24-h water deprivation, d,l-isoproterenol HCl, angiotensin II (AII) and polyethylene glycol (PEG), or control conditions, in within-subjects designs [6].

High impact information on Arg2

• To elucidate the role of AII in immune-mediated renal injury, we studied anti-glomerular basement membrane (GBM) nephritis in AII type 1a receptor (AT1a)-deficient homozygous (AT1a-/-) and wild-type (AT1a+/+) mice [7].
• Amino acid sequences of apo AII, which is considered to be less antiatherogenic, can be used to restore the structure of apo AI and thereby its antiatherogenicity [8].
• Treatment of cells with the AII type 1 receptor antagonist losartan inhibited the mitogenic effects of AII [9].
• By means of a rat aortic smooth muscle (RASM) cell culture model, the effects of angiotensin II (AII) on early proto-oncogene gene expression, DNA synthesis, and cell proliferation were measured and compared to known mitogens [9].
• AII also stimulated smooth muscle cell proliferation, as indicated by an absolute increase in cell number after AII stimulation of RASM cells for 5 d [9].

Chemical compound and disease context of Arg2

• Angiotensin I (AI) and angiotensin II/III (AII/III) were detected by radioimmunoassay in homogenates of isolated liver granulomas from mice infected for 8 wk with Schistosoma mansoni [10].
• Poly ADP-ribosylation of two mouse lymphoma cell lines, L5178Y (LS) and the radiation and alkylating agent resistant derivative AII, was investigated by uptake of [3H]NAD by permeabilised cells into acid-precipitable material that was sensitive to phosphodiesterase but insensitive to DNase and RNase [11].
• Captopril, a specific angiotensin-converting-enzyme (ACE) inhibitor, appreciably decreased AII/III produced by macrophages from modulated granulomas [12].
• The mechanisms of synthesis and secretion of renin and AII are potentially modified by high glucose concentration, suggesting a possible role of AII produced by mesangial cells in diabetic nephropathy [13].
• Losartan, a recently developed nonpeptide angiotensin II (AII) receptor antagonist, was orally administered for 14 days to mice with viral myocarditis, beginning 7 days after encephalomyocarditis virus inoculation [14].

Biological context of Arg2

• Renal AII gene expression was gender-dependent in mice but not in rats [15].
• L-[guanidino-14C]arginine hydrolysis by AII was detected in microdissected tubules and the 14CO2 released from [14C]urea hydrolysis was quantified [15].
• Sequence homology to the human type II arginase, arginase activity data, and immunoprecipitation with an anti-AII antibody confirm the identity of these cloned genes as rodent extrahepatic type II arginases [16].
• Using murine macrophage-like RAW 264.7 cells, we asked if the induction of arginase II would downregulate NO production and hence prevent apoptosis [17].
• On the other hand, transfection with the arginase II plasmid did not prevent apoptosis when a NO donor SNAP or a high concentration (12 mM) of arginine was added [17].

Anatomical context of Arg2

• Immunohistochemical analysis showed that arginase I is induced in macrophages, whereas arginase II is induced in various cell types, including macrophages and myofibroblasts, and roughly colocalizes with the collagen-specific chaperone heat shock protein 47 [18].
• In conclusion, in both genders, AII gene expression is restricted to the PST and localized into mitochondria [15].
• The N-terminal Arg2, Arg3 and Arg4 of human lactoferrin interact with sulphated molecules but not with the receptor present on Jurkat human lymphoblastic T-cells [19].
• Administration of thiorphan , an enkephalin dipeptidyl carboxypeptidase inhibitor, did not potentiate the analgesic effect of D- Arg2 -Met5-enkephalin, whereas it dramatically enhanced the effect of D-Ala2-Met5-enkephalin, when both drugs were administered concomitantly into the cisterna magna of mice [20].
• AI and AII were detected only in neurons and not in glial cells [21].

Associations of Arg2 with chemical compounds

• The elevated arginine levels induce the second arginase (AII) in patient kidney and kidney tissue culture [22].
• N-terminal stretch Arg2, Arg3, Arg4 and Arg5 of human lactoferrin is essential for binding to heparin, bacterial lipopolysaccharide, human lysozyme and DNA [23].
• When dexamethasone and cAMP were further added, both iNOS and arginase II were induced, NO production was much decreased, and apoptosis was prevented [17].
• The results clearly indicate that pharmacological doses of testosterone simultaneously down-regulated the level of OAT protein and up-regulated the expression of arginase II and ODC genes [24].
• Consequently, in kidneys of testosterone-treated mice, L-arginine-derived ornithine produced by arginase II might be preferentially used by ODC for putrescine production rather than by OAT [24].

Regulatory relationships of Arg2

• Testosterone down-regulates ornithine aminotransferase gene and up-regulates arginase II and ornithine decarboxylase genes for polyamines synthesis in the murine kidney [24].
• By immunoblotting we evidenced that AI and AII isoforms were up-regulated in TMps while the inducible and neuronal NOS isoforms were highly expressed in normal Mps [25].

Other interactions of Arg2

• In the AI knockout mouse embryo, no AII overexpression was found [26].
• Arginase II protein began to increase at day 5, increased for up to 10 days, and was decreased at day 14. mRNAs for cationic amino acid transporter-2 and ornithine decarboxylase were induced in a manner similar to that seen with collagen I mRNA [18].
• Finally, in the PST of females, L-arginine-derived ornithine may be a precursor for the renal production of L -glutamate and L-glutamine because high levels of AII, ornithine aminotransferase and glutamine synthetase are expressed in this nephron segment [15].
• Arginase I and arginase II mRNA expression was higher in macrophages from infected BALB/c compared with those from C57BL/6 mice, whereas iNOS mRNA was up-regulated at the same level in both phenotypes [27].
• Results indicate IL-4, in concert with serum, increases AI, but not AII, mRNA in cultured murine macrophages [28].

Analytical, diagnostic and therapeutic context of Arg2

• By the intravenous route, only D- Arg2 -Met5-enkephalin, which induced a most potent analgesia by intracisternal injection, was effective [20].
• Orchidectomy increased the renal level of OAT protein and decreased that of ODC and arginase II [24].
• This study was undertaken to explore the cellular and regional distribution of AI and AII expression in brain using in situ hybridization and immunohistochemistry [21].
• In contrast, most studies, at least in cell culture, suggest that AII may be most highly expressed in cancers of a number of different types [29].
• Arginase II protein was expressed constitutively in wild-type and C/EBPbeta-/- cell lines and was unaltered by 8-Br-cAMP or rmIL-4. rmIL-4-stimulated immortalized C/EBPbeta-/- macrophages demonstrated higher nuclear signal transducer and activator of transcription-6 (STAT6) and phospho-STAT6 content than their +/+ counterparts [30].

References