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Gene Review

NOS2  -  nitric oxide synthase 2, inducible

Bos taurus

Synonyms: NOS2A, iNOS
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Disease relevance of NOS2A

  • Incubation of BAECs with IL-1 beta-prestimulated BVSMCs induced EC toxicity, which was partially inhibited by an inhibitor of NO synthesis, NG-nitro-L-arginine methyl ester, or an inhibitor of iNOS expression, dexamethasone [1].
  • Inasmuch as aminoguanidine is a relatively selective inhibitor of the inducible isoform of nitric oxide synthase (iNOS), we have investigated the effects of hyperglycemia on the retinal nitric oxide (NO) pathway in the presence and absence of aminoguanidine [2].
  • The pancreatic responses in AM and iNOS may play a major role in mediating prolonged disturbances in nutrient use by tissues through their influences on temporal patterns of pancreatic hormone secretion during chronic illness [3].
  • BACKGROUND: Inflammatory related cardiovascular disease, i.e. cardiac allograft rejection, myocarditis, septic shock, are accompanied by cytokine production, which stimulates the expression of inducible nitric oxide (iNOS) [4].
  • We assessed the kinetics of inducible nitric oxide synthase (iNOS) mRNA expression and production of nitric oxide (NO) in bovine alveolar macrophages (AMs) stimulated with purified lipopolysaccharide (LPS) from Pasteurella haemolytica strain 12296 [5].

Psychiatry related information on NOS2A

  • LPS increased CAT-2 mRNA after LPS; GH was associated with a 24% reduction in CAT-2 mRNA content at the peak time response. cNOS activity was 3-fold greater than iNOS after LPS [6].

High impact information on NOS2A

  • These results indicate that single irradiation does not affect Ca(2+) mobilization and eNOS expression but induces the expression of iNOS in BAECs, and the latter property would be beneficial to induce apoptosis in the adjacent tumor cells [7].
  • RESULTS: MSU induced MMP-3 and iNOS expression and NO release in chondrocytes in a p38-dependent manner that did not require interleukin-1 (IL-1), as demonstrated by using IL-1 receptor antagonist [8].
  • CONCLUSION: These findings support the hypothesis that a component of S. aureus can stimulate iNOS in articular cartilage, and that NO generated from this enzyme down-regulates cartilage matrix proteoglycan synthesis [9].
  • Bovine retinal pigmented epithelial cells express an inducible nitric oxide synthase (NOS-2) after activation with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) [10].
  • SB 203580 did not inhibit iNOS activity, as measured by the conversion of arginine to citrulline, when added directly to cultures where the enzyme had already been induced, but had to be present during the induction period [11].

Chemical compound and disease context of NOS2A


Biological context of NOS2A


Anatomical context of NOS2A

  • Immunoreactive iNOS protein was localised in secretory epithelial cells as well as in the lamina muscularis [20].
  • By in situ hybridisation, specific iNOS transcripts were additionally demonstrated in the oviduct epithelium [20].
  • Northern blot analysis revealed increased iNOS mRNA expression in bovine chondrocytes in response to denatured S. aureus stimulation [9].
  • Fibroblast growth factor-2 (FGF-2) inhibited LPS-IFN-gamma-induced nitrite release and NOS-2 messenger RNA accumulation in keratocytes but not in BCE cells [21].
  • These acute complications rapidly progress into a more chronic state characterized by diminished insulin response to feeding stimulus and colocalized increases in pancreatic islet AM and iNOS [3].

Associations of NOS2A with chemical compounds

  • Bovine retinal pigmented epithelial (RPE) cells express an inducible nitric oxide synthase (NOS-2) after activation with interferon (IFN)-gamma and lipopolysaccharide (LPS) [15].
  • Using a 372-bp probe for bovine iNOS we demonstrated inhibition of IL-1-induced mRNA by SB 203580 at both 4 and 24 h following IL-1 treatment [11].
  • METHODS: Nitric oxide (NO) release, and expression of inducible nitric oxide synthase (iNOS) and matrix metalloproteinase 3 (MMP-3) were assessed in cultured chondrocytes treated with MSU [8].
  • Induction of iNOS with subsequent peroxynitrite formation may contribute to bovine cerebral EC death caused by OGD [16].
  • The involvement of iNOS in EC death was suggested by partial reduction of cell death by NO synthase inhibitors, including L-N(G)-(1-iminoethyl)ornithine and nitro-L-arginine, and an NO scavenger, the Fe(2+)-N-methyl-D-glucamine dithiocarbamate complex [16].

Regulatory relationships of NOS2A

  • We conclude that although TNF alpha is able to stimulate cGMP formation in theca cells by inducing the expression of inducible NOS, the mechanism underlying the TNF alpha-mediated inhibition of LH-stimulated prorenin production is independent of its ability to induce cGMP formation [22].

Other interactions of NOS2A


Analytical, diagnostic and therapeutic context of NOS2A


  1. Endothelial cells inhibit NO generation by vascular smooth muscle cells. Role of transforming growth factor-beta. López Farré, A., Mosquera, J.R., Sánchez de Miguel, L., Millás, I., de Frutos, T., Montón, M., Sierra, M.P., Riesco, A., Casado, S. Arterioscler. Thromb. Vasc. Biol. (1996) [Pubmed]
  2. Diabetes-induced nitrative stress in the retina, and correction by aminoguanidine. Du, Y., Smith, M.A., Miller, C.M., Kern, T.S. J. Neurochem. (2002) [Pubmed]
  3. Underlying disease stress augments plasma and tissue adrenomedullin (AM) responses to endotoxin: colocalized increases in AM and inducible nitric oxide synthase within pancreatic islets. Elsasser, T.H., Sartin, J.L., Martínez, A., Kahl, S., Montuenga, L., Pío, R., Fayer, R., Miller, M.J., Cuttitta, F. Endocrinology (1999) [Pubmed]
  4. Aspirin inhibits inducible nitric oxide synthase expression and tumour necrosis factor-alpha release by cultured smooth muscle cells. Sánchez de Miguel, L., de Frutos, T., González-Fernández, F., del Pozo, V., Lahoz, C., Jiménez, A., Rico, L., García, R., Aceituno, E., Millás, I., Gómez, J., Farré, J., Casado, S., López-Farré, A. Eur. J. Clin. Invest. (1999) [Pubmed]
  5. Induction of nitric oxide production by bovine alveolar macrophages in response to Pasteurella haemolytica A1. Yoo, H.S., Rutherford, M.S., Maheswaran, S.K., Srinand, S., Ames, T.R. Microb. Pathog. (1996) [Pubmed]
  6. Mechanisms underlying growth hormone effects in augmenting nitric oxide production and protein tyrosine nitration during endotoxin challenge. Elsasser, T.H., Kahl, S., MacLeod, C., Nicholson, B., Sartin, J.L., Li, C. Endocrinology (2004) [Pubmed]
  7. Tumor cell apoptosis by irradiation-induced nitric oxide production in vascular endothelium. Hirakawa, M., Oike, M., Masuda, K., Ito, Y. Cancer Res. (2002) [Pubmed]
  8. Proline-rich tyrosine kinase 2 and Src kinase signaling transduce monosodium urate crystal-induced nitric oxide production and matrix metalloproteinase 3 expression in chondrocytes. Liu, R., Lioté, F., Rose, D.M., Merz, D., Terkeltaub, R. Arthritis Rheum. (2004) [Pubmed]
  9. Staphylococcus aureus stimulates inducible nitric oxide synthase in articular cartilage. Jang, D., Williams, R.J., Wang, M.X., Wei, A.Q., Murrell, G.A. Arthritis Rheum. (1999) [Pubmed]
  10. Role of interferon regulatory factor-1 and mitogen-activated protein kinase pathways in the induction of nitric oxide synthase-2 in retinal pigmented epithelial cells. Faure, V., Hecquet, C., Courtois, Y., Goureau, O. J. Biol. Chem. (1999) [Pubmed]
  11. SB 203580 inhibits p38 mitogen-activated protein kinase, nitric oxide production, and inducible nitric oxide synthase in bovine cartilage-derived chondrocytes. Badger, A.M., Cook, M.N., Lark, M.W., Newman-Tarr, T.M., Swift, B.A., Nelson, A.H., Barone, F.C., Kumar, S. J. Immunol. (1998) [Pubmed]
  12. Minocycline inhibits the production of inducible nitric oxide synthase in articular chondrocytes. Sadowski, T., Steinmeyer, J. J. Rheumatol. (2001) [Pubmed]
  13. Are free radicals responsible for endothelial cell killing of Staphylococcus aureus? Zhang, B., Centra, M., Cao, G.L., Ratych, R.E., Domachowske, J.B., Malech, H.L., Rosen, G.M. Immunol. Lett. (1997) [Pubmed]
  14. Induction of nitric oxide synthase in bovine mononuclear phagocytes is differentiation stage-dependent. Jungi, T.W., Thöny, M., Brcic, M., Adler, B., Pauli, U., Peterhans, E. Immunobiology (1996) [Pubmed]
  15. Inhibition of inducible nitric oxide synthase expression by interferons alpha and beta in bovine retinal pigmented epithelial cells. Faure, V., Courtois, Y., Goureau, O. J. Biol. Chem. (1997) [Pubmed]
  16. Oxygen-glucose deprivation induces inducible nitric oxide synthase and nitrotyrosine expression in cerebral endothelial cells. Xu, J., He, L., Ahmed, S.H., Chen, S.W., Goldberg, M.P., Beckman, J.S., Hsu, C.Y. Stroke (2000) [Pubmed]
  17. Inhibition of interleukin-1-induced proteoglycan degradation and nitric oxide production in bovine articular cartilage/chondrocyte cultures by the natural product, hymenialdisine. Badger, A.M., Cook, M.N., Swift, B.A., Newman-Tarr, T.M., Gowen, M., Lark, M. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  18. Gene transfer with inducible nitric oxide synthase decreases production of urea by arginase in pulmonary arterial endothelial cells. Stanley, K.P., Chicoine, L.G., Young, T.L., Reber, K.M., Lyons, C.R., Liu, Y., Nelin, L.D. Am. J. Physiol. Lung Cell Mol. Physiol. (2006) [Pubmed]
  19. Involvement of pro-inflammatory cytokines, mediators of inflammation, and basic fibroblast growth factor in prostaglandin F2alpha-induced luteolysis in bovine corpus luteum. Neuvians, T.P., Schams, D., Berisha, B., Pfaffl, M.W. Biol. Reprod. (2004) [Pubmed]
  20. Region-specific expression of nitric oxide synthases in the bovine oviduct during the oestrous cycle and in vitro. Ulbrich, S.E., Rehfeld, S., Bauersachs, S., Wolf, E., Rottmayer, R., Hiendleder, S., Vermehren, M., Sinowatz, F., Meyer, H.H., Einspanier, R. J. Endocrinol. (2006) [Pubmed]
  21. Expression of inducible nitric oxide synthase in bovine corneal endothelial cells and keratocytes in vitro after lipopolysaccharide and cytokines stimulation. Dighiero, P., Behar-Cohen, F., Courtois, Y., Goureau, O. Invest. Ophthalmol. Vis. Sci. (1997) [Pubmed]
  22. Stimulation of nitric oxide-cyclic guanosine monophosphate pathway in bovine ovarian theca cells by tumor necrosis factor alpha (TNF alpha). Is this pathway implicated in the TNF alpha-induced inhibition of luteinizing hormone-stimulated prorenin production? Brunswig-Spickenheier, B., Mukhopadhyay, A.K. Biol. Reprod. (1997) [Pubmed]
  23. Octacalcium phosphate crystals directly stimulate expression of inducible nitric oxide synthase through p38 and JNK mitogen-activated protein kinases in articular chondrocytes. Ea, H.K., Uzan, B., Rey, C., Lioté, F. Arthritis Res. Ther. (2005) [Pubmed]
  24. Cationic amino acid transport across the blood-brain barrier is mediated exclusively by system y+. O'Kane, R.L., Viña, J.R., Simpson, I., Zaragozá, R., Mokashi, A., Hawkins, R.A. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  25. Nitric oxide, an autocrine regulator of wound fibroblast synthetic function. Schäffer, M.R., Efron, P.A., Thornton, F.J., Klingel, K., Gross, S.S., Barbul, A. J. Immunol. (1997) [Pubmed]
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