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Gene Review

Arg2  -  arginase type II

Mus musculus

Synonyms: AII, AU022422, Arginase-2, mitochondrial, Kidney-type arginase, Non-hepatic arginase, ...
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Disease relevance of Arg2


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


Chemical compound and disease context of Arg2


Biological context of Arg2


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


Regulatory relationships of Arg2


Other interactions of Arg2


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].


  1. Ornithine deficiency in the arginase double knockout mouse. Deignan, J.L., Livesay, J.C., Yoo, P.K., Goodman, S.I., O'brien, W.E., Iyer, R.K., Cederbaum, S.D., Grody, W.W. Mol. Genet. Metab. (2006) [Pubmed]
  2. Decrease in lung nitric oxide production after peritonitis in mice with sickle cell disease. Bartolucci, P., Ngo, M.T., Beuzard, Y., Galactéros, F., Saber, G., Rideau, D., Eddahibi, S., Maitre, B., Adnot, S., Delclaux, C. Crit. Care Med. (2007) [Pubmed]
  3. Protein composition determines the anti-atherogenic properties of HDL in transgenic mice. Schultz, J.R., Verstuyft, J.G., Gong, E.L., Nichols, A.V., Rubin, E.M. Nature (1993) [Pubmed]
  4. Helicobacter pylori induces macrophage apoptosis by activation of arginase II. Gobert, A.P., Cheng, Y., Wang, J.Y., Boucher, J.L., Iyer, R.K., Cederbaum, S.D., Casero, R.A., Newton, J.C., Wilson, K.T. J. Immunol. (2002) [Pubmed]
  5. Angiotensin converting enzyme inhibitor captopril suppresses a genetic polydipsic behavior. Silverstein, E., Friedland, J. Pharmacol. Biochem. Behav. (1990) [Pubmed]
  6. Drinking behavior in the spiny mouse (Acomys cahirinus) following putative dipsogenic challenges. Czech, D.A., Vander Zanden, J.M. Pharmacol. Biochem. Behav. (1991) [Pubmed]
  7. Angiotensin II plays a pathogenic role in immune-mediated renal injury in mice. Hisada, Y., Sugaya, T., Yamanouchi, M., Uchida, H., Fujimura, H., Sakurai, H., Fukamizu, A., Murakami, K. J. Clin. Invest. (1999) [Pubmed]
  8. Substitution of the carboxyl-terminal domain of apo AI with apo AII sequences restores the potential of HDL to reduce the progression of atherosclerosis in apo E knockout mice. Holvoet, P., Danloy, S., Deridder, E., Lox, M., Bernar, H., Dhoest, A., Collen, D. J. Clin. Invest. (1998) [Pubmed]
  9. Angiotensin II induces delayed mitogenesis and cellular proliferation in rat aortic smooth muscle cells. Correlation with the expression of specific endogenous growth factors and reversal by suramin. Weber, H., Taylor, D.S., Molloy, C.J. J. Clin. Invest. (1994) [Pubmed]
  10. Isolated liver granulomas of murine Schistosoma mansoni contain components of the angiotensin system. Weinstock, J.V., Blum, A.M. J. Immunol. (1983) [Pubmed]
  11. Poly (ADP-ribose) metabolism in alkylated mouse L5178Y cells. Boyle, J.M. Carcinogenesis (1985) [Pubmed]
  12. Effects of granuloma modulation induced by regulatory-T-lymphocyte activity on angiotensin II/III production by granuloma macrophages in murine schistosomiasis mansoni. Weinstock, J.V., Blum, A.M. Cell. Immunol. (1985) [Pubmed]
  13. Renin similar to the submaxillary gland form is expressed in mouse mesangial cells: subcellular localization and all generation under control and glucose-stimulated conditions. Leite, C.A., Cristovam, P.C., Leitão, A.A., Miranda, A., Andrade, M.C., Di Marco, G., Casarini, D.E., Boim, M.A. Cell. Physiol. Biochem. (2003) [Pubmed]
  14. Comparative effects of losartan, captopril, and enalapril on murine acute myocarditis due to encephalomyocarditis virus. Araki, M., Kanda, T., Imai, S., Suzuki, T., Murata, K., Kobayashi, I. J. Cardiovasc. Pharmacol. (1995) [Pubmed]
  15. Localization and differential expression of arginase II in the kidney of male and female mice. Levillain, O., Balvay, S., Peyrol, S. Pflugers Arch. (2005) [Pubmed]
  16. Cloning and characterization of the mouse and rat type II arginase genes. Iyer, R.K., Bando, J.M., Jenkinson, C.P., Vockley, J.G., Kim, P.S., Kern, R.M., Cederbaum, S.D., Grody, W.W. Mol. Genet. Metab. (1998) [Pubmed]
  17. Arginase II downregulates nitric oxide (NO) production and prevents NO-mediated apoptosis in murine macrophage-derived RAW 264.7 cells. Gotoh, T., Mori, M. J. Cell Biol. (1999) [Pubmed]
  18. Induction of arginase I and II in bleomycin-induced fibrosis of mouse lung. Endo, M., Oyadomari, S., Terasaki, Y., Takeya, M., Suga, M., Mori, M., Gotoh, T. Am. J. Physiol. Lung Cell Mol. Physiol. (2003) [Pubmed]
  19. 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. Legrand, D., van Berkel, P.H., Salmon, V., van Veen, H.A., Slomianny, M.C., Nuijens, J.H., Spik, G. Biochem. J. (1997) [Pubmed]
  20. Opioid activity of enkephalin analogues containing the kyotorphin-related structure in the N-terminus. Amano, H., Morimoto, Y., Kaneko, S., Takagi, H. Neuropharmacology (1984) [Pubmed]
  21. Expression of arginase isozymes in mouse brain. Yu, H., Iyer, R.K., Kern, R.M., Rodriguez, W.I., Grody, W.W., Cederbaum, S.D. J. Neurosci. Res. (2001) [Pubmed]
  22. Arginase induction by sodium phenylbutyrate in mouse tissues and human cell lines. Kern, R.M., Yang, Z., Kim, P.S., Grody, W.W., Iyer, R.K., Cederbaum, S.D. Mol. Genet. Metab. (2007) [Pubmed]
  23. N-terminal stretch Arg2, Arg3, Arg4 and Arg5 of human lactoferrin is essential for binding to heparin, bacterial lipopolysaccharide, human lysozyme and DNA. van Berkel, P.H., Geerts, M.E., van Veen, H.A., Mericskay, M., de Boer, H.A., Nuijens, J.H. Biochem. J. (1997) [Pubmed]
  24. Testosterone down-regulates ornithine aminotransferase gene and up-regulates arginase II and ornithine decarboxylase genes for polyamines synthesis in the murine kidney. Levillain, O., Diaz, J.J., Blanchard, O., Déchaud, H. Endocrinology (2005) [Pubmed]
  25. Arginine metabolic pathways involved in the modulation of tumor-induced angiogenesis by macrophages. Davel, L.E., Jasnis, M.A., de la Torre, E., Gotoh, T., Diament, M., Magenta, G., Sacerdote de Lustig, E., Sales, M.E. FEBS Lett. (2002) [Pubmed]
  26. Arginase expression in mouse embryonic development. Yu, H., Iyer, R.K., Yoo, P.K., Kern, R.M., Grody, W.W., Cederbaum, S.D. Mech. Dev. (2002) [Pubmed]
  27. Mouse strain susceptibility to trypanosome infection: an arginase-dependent effect. Duleu, S., Vincendeau, P., Courtois, P., Semballa, S., Lagroye, I., Daulouède, S., Boucher, J.L., Wilson, K.T., Veyret, B., Gobert, A.P. J. Immunol. (2004) [Pubmed]
  28. Regulation of arginase isoforms I and II by IL-4 in cultured murine peritoneal macrophages. Louis, C.A., Mody, V., Henry, W.L., Reichner, J.S., Albina, J.E. Am. J. Physiol. (1999) [Pubmed]
  29. Arginases I and II: do their functions overlap? Cederbaum, S.D., Yu, H., Grody, W.W., Kern, R.M., Yoo, P., Iyer, R.K. Mol. Genet. Metab. (2004) [Pubmed]
  30. Macrophage arginase regulation by CCAAT/enhancer-binding protein beta. Albina, J.E., Mahoney, E.J., Daley, J.M., Wesche, D.E., Morris, S.M., Reichner, J.S. Shock (2005) [Pubmed]
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