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Signal transduction by nitric oxide in cellular stress responses

  • Bruce Demple
Chapter
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 37)

Abstract

Nitric oxide (NO) has received wide attention as a biological signaling molecule that uses cyclic GMP as a cellular second messenger. Other work has supported roles for cysteine oxidation or nitrosylation as signaling events. Recent studies in bacteria and mammalian cells now point to the existence of at least two other pathways independent of cGMP. For theE. coliSoxR protein, signaling occurs by nitrosylation of its binuclear iron-sulfur clusters, a reaction that is unprecedented in gene activation. In intact cells, these nitrosylated centers are very rapidly replaced by unmodified iron-sulfur clusters, a result that points to the existence of an active repair pathway for this type of protein damage. Exposure of mammalian cells to NO elicits an adaptive resistance that confers elevated resistance of the cells to higher levels of NO. This resistance in many cell types involves the important defense protein heme oxygenase 1, although the mechanism by which this enzyme mediates NO resistance remains unknown. Induction of heme oxygenase in some cell types occurs through the stabilization of its mRNA. NO-induced stabilization of mRNA is mediated by pre-existing proteins and points to the existence of an important new signaling pathway that counteracts the damage and stress exerted by this free radical. (Mol Cell Biochem 234/235: 11–18, 2002)

Key words

signal transduction stress responses nitric oxide 

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References

  1. 1.
    Sies H (ed): Oxidative Stress: Oxidants and Antioxidants. Academic Press, London, 1991Google Scholar
  2. 2.
    Sies H: Biochemistry of oxidative stress. Angew Chem Int Ed Eng125: 1058–1071,1986CrossRefGoogle Scholar
  3. 3.
    Demple B, Harrison L: Repair of oxidative damage to DNA: Enzymology and biology. Annu Rev Biochem 63: 915–948, 1994PubMedCrossRefGoogle Scholar
  4. 4.
    Moskovitz J, Weissbach H, Brot N: Cloning the expression of a mammalian gene involved in the reduction of methionine sulfoxide residues in proteins. Proc Natl Acad Sci USA 93: 2095–2099, 1996PubMedCrossRefGoogle Scholar
  5. 5.
    Demple B: Redox-regulated gene expression. In: K. Adolph (ed). Methods: A Companion to Methods in Enzymology. 1997, pp 265–400Google Scholar
  6. 6.
    Hidalgo E, Demple B: Adaptive responses to oxidative stress: ThesoxRSandoxyRregulons. In: E.C.C. Lin, A.S. Lynch (eds). Regulation of Gene Expression inEscherichia coli.R.G. Landes, Austin, TX, 1996, pp 435–452CrossRefGoogle Scholar
  7. 7.
    Zheng M, Wang X, Templeton LJ, Smulski DR, LaRossa RA, Storz G: DNA microarray-mediated transcriptional profiling of theEscherichia coliresponse to hydrogen peroxide. J Bacteriol 183: 4562–4570, 2001PubMedCrossRefGoogle Scholar
  8. 8.
    Pomposiello PJ, Bennik MH, Demple B: Genome-wide transcriptional profiling of theEscherichia coliresponses to superoxide stress and sodium salicylate. J Bacteriol 183: 3890–3902, 2001PubMedCrossRefGoogle Scholar
  9. 9.
    Zheng M, Aslund F, Storz G: Activation of the OxyR transcription factor by reversible disulfide bond formation. Science 279: 1718–1721, 1998PubMedCrossRefGoogle Scholar
  10. 10.
    Carmel-Harel O, Storz G: Roles of the glutathione-and thioredoxindependent reduction systems in theEscherichia coliandSaccharomyces cerevisiaeresponses to oxidative stress. Annu Rev Microbiol 54: 439–461, 2000PubMedCrossRefGoogle Scholar
  11. 11.
    Jakob U, Muse W, Eser M, Bardwell JC: Chaperone activity with a redox switch. Cell 96: 341–352, 1999PubMedCrossRefGoogle Scholar
  12. 12.
    Gaudu P, Weiss B: SoxR, a [2Fe-2S] transcription factor, is active only in its oxidized form. Proc Natl Acad Sci USA 93: 10094–10098, 1996PubMedCrossRefGoogle Scholar
  13. 13.
    Hidalgo E, Ding H, Demple B: Redox signal transduction: Mutations shifting [2Fe-2S] centers of the SoxR sensor-regulator to the oxidized form. Cell 88: 121–129, 1997PubMedCrossRefGoogle Scholar
  14. 14.
    Hidalgo E, Demple B: An iron-sulfur center essential for transcriptional activation by the redox-sensing SoxR protein. EMBO J 13: 138–146, 1994PubMedGoogle Scholar
  15. 15.
    Hidalgo E, Ding H, Demple B: Redox signal transduction via iron-sulfur clusters in the SoxR transcription factor. Trends Biochem Sci 22: 207 210, 1997Google Scholar
  16. 16.
    Hidalgo E, Bollinger JM Jr, Bradley TM, Walsh CT, Demple B: Binuclear [2Fe-2S] clusters in theEscherichia coliSoxR protein and role of the metal centers in transcription. J Biol Chem 270: 20908–20914, 1995PubMedCrossRefGoogle Scholar
  17. 17.
    Hidalgo E, Leautaud V, Demple B: The redox-regulated SoxR protein acts from a single DNA site as a repressor and an allosteric activator. EMBO J 17: 2629–2636, 1998PubMedCrossRefGoogle Scholar
  18. 18.
    Ding H, Demple B:In vivokinetics of a redox-regulated transcriptional switch. Proc Natl Acad Sci USA 94: 8445–8449, 1997PubMedCrossRefGoogle Scholar
  19. 19.
    Ignarro LI: Biosynthesis and metabolism of endothelial-derived nitric oxide. Annu Rev Pharmacol Toxicol 30: 535–560, 1990PubMedCrossRefGoogle Scholar
  20. 20.
    MacMicking J, Xie QW, Nathan C: Nitric oxide and macrophage function. Annu Rev Immunol 15: 323–350, 1997PubMedCrossRefGoogle Scholar
  21. 21.
    Nunoshiba T, deRojas-Walker T, Wishnok JS, Tannenbaum SR, Demple B: Activation by nitric oxide of an oxidative-stress response that defendsEscherichia coliagainst activated macrophages. Proc Natl Acad Sci USA 90: 9993 9997, 1993Google Scholar
  22. 22.
    Nunoshiba T, deRojas-Walker T, Tannenbaum SR, Demple B: Roles of nitric oxide in inducible resistance ofEscherichia colito activated murine macrophages. Infect Immun 63: 794–798, 1995PubMedGoogle Scholar
  23. 23.
    Ding H, Demple B: Direct nitric oxide signal transduction via nitrosylation of iron-sulfur centers in the SoxR transcription activator. Proc Natl Acad Sci USA 97: 5146–5150, 2000PubMedCrossRefGoogle Scholar
  24. 24.
    Lancaster JR Jr, Hibbs JB Jr: EPR demonstration of iron-nitrosyl complex formation by cytotoxic activated macrophages. Proc Natl Acad Sci USA 87: 1223–1227, 1990PubMedCrossRefGoogle Scholar
  25. 25.
    Pellat C, Henry Y, Drapier JC: IFN-gamma-activated macrophages: Detection by electron paramagnetic resonance of complexes between L-arginine-derived nitric oxide and non-heme iron proteins. Biochem Biophys Res Commun 166: 119–125, 1990PubMedCrossRefGoogle Scholar
  26. 26.
    Hidalgo E, Demple B: Activation of SoxR-dependent transcriptionin vitroby noncatalytic or NifS-mediated assembly of [2Fe-2S] clusters into apo-SoxR. J Biol Chem 271: 7269–7272, 1996PubMedCrossRefGoogle Scholar
  27. 27.
    Ding H, Demple B: Thiol-mediated disassembly and reassembly of [2Fe-2S] clusters in the redox-regulated transcription factor SoxR. Biochemistry 37: 17280–17286, 1998PubMedCrossRefGoogle Scholar
  28. 28.
    Rogers PA, Ding H: L-cysteine-mediated destabilization of dinitrosyl iron complexes in proteins. J Biol Chem 276: 30980–30986, 2001PubMedCrossRefGoogle Scholar
  29. 29.
    Heldwein EE, Brennan RG: Crystal structure of the transcription activator BmrR bound to DNA and a drug. Nature 409: 378–382, 2001PubMedCrossRefGoogle Scholar
  30. 30.
    Beckman JS, Koppenol WH: Nitric oxide, superoxide, and peroxynitrite: The good, the bad, and ugly. Am J Physiol 271: C1424–1437, 1996Google Scholar
  31. 31.
    Bredt DS, Hwang PM, Glatt CE, Lowenstein C, Reed RR, Snyder SH: Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase. Nature 351: 714–718, 1991PubMedCrossRefGoogle Scholar
  32. 32.
    Durham HD, Dahrouge S, Cashman NR: Evaluation of the spinal cord neuron X neuroblastoma hybrid cell line NSC-34 as a model for neurotoxicity testing. Neurotoxicology 14: 387–395, 1993PubMedGoogle Scholar
  33. 33.
    Bishop A, Marquis JC, Cashman NR, Demple B: Adaptive resistance to nitric oxide in motor neurons. Free Radic Biol Med 26: 978–986, 1999PubMedCrossRefGoogle Scholar
  34. 34.
    Kim Y-M, Bergonia H, Lancaster JRJ: Nitrogen oxide-induced auto-protection in isolated rat hepatocytes. FEBS Lett 374: 228–232, 1995PubMedCrossRefGoogle Scholar
  35. 35.
    Motterlini R, Foresti R, Intaglietta M, Winslow RM: NO-mediated activation of heme oxygenase: Endogenous cytoprotection against oxidative stress to endothelium. Am J Physiol 270: H107–114, 1996PubMedGoogle Scholar
  36. 36.
    Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN: Bilirubin is an antioxidant of possible physiological importance. Science 235: 1043–1046, 1987PubMedCrossRefGoogle Scholar
  37. 37.
    Steiner AA, Branco LG: Carbon monoxide is the heme oxygenase product with a pyretic action: Evidence for a cGMP signaling pathway. Am J Physiol Regul Integr Comp Physiol 280: R448–457, 2001Google Scholar
  38. 38.
    Brouard S, Otterbein LE, Anrather J, Tobiasch E, Bach FH, Choi AM, Soares MP: Carbon monoxide generated by heme oxygen-ase 1 suppresses endothelial cell apoptosis. J Exp Med 192: 1015–1026, 2000CrossRefGoogle Scholar
  39. 39.
    Vile GF, Basu-Modak S, Waltner C, Tyrrell RM: Heme oxygenase 1 mediates an adaptive response to oxidative stress in human skin fibroblasts. Proc Natl Acad Sci USA 91: 2607–2610, 1994PubMedCrossRefGoogle Scholar
  40. 40.
    Hentze MW, Kühn LC: Molecular control of vertebrate iron metabolism: mRNA-based regulatory circuits operated by iron, nitric oxide and oxidative stress. Proc Natl Acad Sci USA 93: 8175–8182, 1996PubMedCrossRefGoogle Scholar
  41. 41.
    Liu Y, Ortiz de Montellano PR: Reaction intermediates and single turnover rate constants for the oxidation of heme by human heme oxygenase-1. J Biol Chem 275: 5297–307, 2000PubMedCrossRefGoogle Scholar
  42. 42.
    Marquis JC, Demple B: Complex genetic response of human cells to sublethal levels of pure nitric oxide. Cancer Res 58: 3435–3440, 1998PubMedGoogle Scholar
  43. 43.
    Tyrrell RM: Approaches to define pathways of redox regulation of a eukaryotic gene: The heme oxygenase 1 example. Methods 11: 313–318, 1997PubMedCrossRefGoogle Scholar
  44. 44.
    Bouton C, Demple B: Nitric oxide-inducible expression of heme oxygenase-1 in human cells. Translation-independent stabilization of the mRNA and evidence for direct action of nitric oxide. J Biol Chem 275: 32688–32693,2000PubMedCrossRefGoogle Scholar
  45. 45.
    Hobbs AJ, Ignarro LJ: Nitric oxide-cyclic GMP signal transduction system. Meth Enzymol 269: 134–148, 1996PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Bruce Demple
    • 1
  1. 1.Department of Cancer Cell BiologyHarvard School of Public HealthBostonUSA

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