Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Apr 1;90(7):3024–3027. doi: 10.1073/pnas.90.7.3024

In vivo expression of inducible nitric oxide synthase in experimentally induced neurologic diseases.

H Koprowski 1, Y M Zheng 1, E Heber-Katz 1, N Fraser 1, L Rorke 1, Z F Fu 1, C Hanlon 1, B Dietzschold 1
PMCID: PMC46229  PMID: 7681993

Abstract

The purpose of this study was to investigate the induction of inducible nitric oxide synthase (iNOS) mRNA in the brain tissue of rats and mice under the following experimental conditions: in rats infected with borna disease virus and rabies virus, in mice infected with herpes simplex virus, and in rats after the induction of experimental allergic encephalitis. The results showed that iNOS mRNA, normally nondetectable in the brain, was present in animals after viral infection or after induction of experimental allergic encephalitis. The induction of iNOS mRNA coincided with the severity of clinical signs and in some cases with the presence of inflammatory cells in the brain. The results indicate that nitric oxide produced by cells induced by iNOS may be the toxic factor accounting for cell damage and this may open the door to approaches to the study of the pathogenesis of neurological diseases.

Full text

PDF
3027

Images in this article

3025Fig. 1
on p.3025
3026Fig. 2
on p.3026
3026Fig. 3
on p.3026
3026Fig. 4
on p.3026

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Auffray C., Rougeon F. Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem. 1980 Jun;107(2):303–314. doi: 10.1111/j.1432-1033.1980.tb06030.x. [DOI] [PubMed] [Google Scholar]
  2. Beckman J. S., Beckman T. W., Chen J., Marshall P. A., Freeman B. A. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1620–1624. doi: 10.1073/pnas.87.4.1620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Billiar T. R., Curran R. D., Harbrecht B. G., Stuehr D. J., Demetris A. J., Simmons R. L. Modulation of nitrogen oxide synthesis in vivo: NG-monomethyl-L-arginine inhibits endotoxin-induced nitrate/nitrate biosynthesis while promoting hepatic damage. J Leukoc Biol. 1990 Dec;48(6):565–569. doi: 10.1002/jlb.48.6.565. [DOI] [PubMed] [Google Scholar]
  4. Cross A. H., Cannella B., Brosnan C. F., Raine C. S. Homing to central nervous system vasculature by antigen-specific lymphocytes. I. Localization of 14C-labeled cells during acute, chronic, and relapsing experimental allergic encephalomyelitis. Lab Invest. 1990 Aug;63(2):162–170. [PubMed] [Google Scholar]
  5. Denis M. Tumor necrosis factor and granulocyte macrophage-colony stimulating factor stimulate human macrophages to restrict growth of virulent Mycobacterium avium and to kill avirulent M. avium: killing effector mechanism depends on the generation of reactive nitrogen intermediates. J Leukoc Biol. 1991 Apr;49(4):380–387. doi: 10.1002/jlb.49.4.380. [DOI] [PubMed] [Google Scholar]
  6. Ding A. H., Nathan C. F., Stuehr D. J. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J Immunol. 1988 Oct 1;141(7):2407–2412. [PubMed] [Google Scholar]
  7. Galea E., Feinstein D. L., Reis D. J. Induction of calcium-independent nitric oxide synthase activity in primary rat glial cultures. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10945–10949. doi: 10.1073/pnas.89.22.10945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Happ M. P., Heber-Katz E. Differences in the repertoire of the Lewis rat T cell response to self and non-self myelin basic proteins. J Exp Med. 1988 Feb 1;167(2):502–513. doi: 10.1084/jem.167.2.502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hibbs J. B., Jr, Westenfelder C., Taintor R., Vavrin Z., Kablitz C., Baranowski R. L., Ward J. H., Menlove R. L., McMurry M. P., Kushner J. P. Evidence for cytokine-inducible nitric oxide synthesis from L-arginine in patients receiving interleukin-2 therapy. J Clin Invest. 1992 Mar;89(3):867–877. doi: 10.1172/JCI115666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lowenstein C. J., Glatt C. S., Bredt D. S., Snyder S. H. Cloned and expressed macrophage nitric oxide synthase contrasts with the brain enzyme. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6711–6715. doi: 10.1073/pnas.89.15.6711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. MacMicking J. D., Willenborg D. O., Weidemann M. J., Rockett K. A., Cowden W. B. Elevated secretion of reactive nitrogen and oxygen intermediates by inflammatory leukocytes in hyperacute experimental autoimmune encephalomyelitis: enhancement by the soluble products of encephalitogenic T cells. J Exp Med. 1992 Jul 1;176(1):303–307. doi: 10.1084/jem.176.1.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Maeda H., Akaike T. Oxygen free radicals as pathogenic molecules in viral diseases. Proc Soc Exp Biol Med. 1991 Nov;198(2):721–727. doi: 10.3181/00379727-198-43309c. [DOI] [PubMed] [Google Scholar]
  13. Marsden P. A., Ballermann B. J. Tumor necrosis factor alpha activates soluble guanylate cyclase in bovine glomerular mesangial cells via an L-arginine-dependent mechanism. J Exp Med. 1990 Dec 1;172(6):1843–1852. doi: 10.1084/jem.172.6.1843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J. 1992 Sep;6(12):3051–3064. [PubMed] [Google Scholar]
  15. Nussler A. K., Di Silvio M., Billiar T. R., Hoffman R. A., Geller D. A., Selby R., Madariaga J., Simmons R. L. Stimulation of the nitric oxide synthase pathway in human hepatocytes by cytokines and endotoxin. J Exp Med. 1992 Jul 1;176(1):261–264. doi: 10.1084/jem.176.1.261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ochoa J. B., Udekwu A. O., Billiar T. R., Curran R. D., Cerra F. B., Simmons R. L., Peitzman A. B. Nitrogen oxide levels in patients after trauma and during sepsis. Ann Surg. 1991 Nov;214(5):621–626. doi: 10.1097/00000658-199111000-00013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rock D. L., Fraser N. W. Detection of HSV-1 genome in central nervous system of latently infected mice. Nature. 1983 Apr 7;302(5908):523–525. doi: 10.1038/302523a0. [DOI] [PubMed] [Google Scholar]
  18. Schneider R. J., Shenk T. Impact of virus infection on host cell protein synthesis. Annu Rev Biochem. 1987;56:317–332. doi: 10.1146/annurev.bi.56.070187.001533. [DOI] [PubMed] [Google Scholar]
  19. Shankar V., Dietzschold B., Koprowski H. Direct entry of rabies virus into the central nervous system without prior local replication. J Virol. 1991 May;65(5):2736–2738. doi: 10.1128/jvi.65.5.2736-2738.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Shankar V., Kao M., Hamir A. N., Sheng H., Koprowski H., Dietzschold B. Kinetics of virus spread and changes in levels of several cytokine mRNAs in the brain after intranasal infection of rats with Borna disease virus. J Virol. 1992 Feb;66(2):992–998. doi: 10.1128/jvi.66.2.992-998.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Simmons M. L., Murphy S. Induction of nitric oxide synthase in glial cells. J Neurochem. 1992 Sep;59(3):897–905. doi: 10.1111/j.1471-4159.1992.tb08328.x. [DOI] [PubMed] [Google Scholar]
  22. Simpson L. L. The study of clostridial and related toxins. The search for unique mechanisms and common denominators. J Physiol (Paris) 1990;84(2):143–151. [PubMed] [Google Scholar]
  23. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  24. Wright C. D., Mülsch A., Busse R., Osswald H. Generation of nitric oxide by human neutrophils. Biochem Biophys Res Commun. 1989 Apr 28;160(2):813–819. doi: 10.1016/0006-291x(89)92506-0. [DOI] [PubMed] [Google Scholar]
  25. Xie Q. W., Cho H. J., Calaycay J., Mumford R. A., Swiderek K. M., Lee T. D., Ding A., Troso T., Nathan C. Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science. 1992 Apr 10;256(5054):225–228. doi: 10.1126/science.1373522. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES