Enzymatic Targets of Nitric Oxide as Detected by EPR Spectroscopy within Mammal Cells

  • Yann A. Henry
  • Béatrice Ducastel
  • Annie Guissani


We concluded in chapter 6 that all metalloproteins are potential targets of NO, as proven by EPR spectroscopy, which is too unspecific to be a really interesting statement. We now turn to some more biologically relevant aspects of NO binding. Its production from L-arginine catalyzed by the inducible NO-synthase (iNOS, NOS II) in murine macrophages and their tumoral target cells was the simplest case to characterize at the molecular level by EPR spectroscopy. [FeS]-containing proteins and ribonucleotide reductase responsible for basic vital cellular functions such as mitochondrial respiration and DNA replication were the earliest enzymatic targets characterized in whole cultured mammal cells.


Nitric Oxide Electron Paramagnetic Resonance Guanylate Cyclase Ribonucleotide Reductase Soluble Guanylate Cyclase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ignarro LJ. Biosynthesis and metabolism of endothelium-derived nitric oxide. Annu Rev Pharmacol Toxicol 1990; 30:535–560.PubMedCrossRefGoogle Scholar
  2. 2.
    Ignarro LJ. Haem-dependent activation of guanylate cyclase and cyclic GMP formation by endogenous nitric oxide: a unique transduction mechanism for transcellular signalling. Pharmacol Toxicol 1990; 67:1–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Ignarro LJ. Signal transduction mechanisms involving nitric oxide. Biochem Pharmacol 1991; 41:485–490.PubMedCrossRefGoogle Scholar
  4. 4.
    Garbers DL, Lowe DG. Guanylyl cyclase receptors. J Biol Chem 1994; 269:30741–30744.PubMedGoogle Scholar
  5. 5.
    Arnold WP, Mittal CK, Katsuki S et al. Nitric oxide activates guanylate cyclase and increases guanosine 3′:5′-cyclic monophosphate levels in various tissue preparations. Proc Natl Acad Sci USA 1977; 74:3203–3207.PubMedCrossRefGoogle Scholar
  6. 6.
    Miki N, Kawabe Y, Kuriyama K. Activation of cerebral guanylate cyclase by nitric oxide. Biochem Biophys Res Commun 1977; 75:851–856.PubMedCrossRefGoogle Scholar
  7. 7.
    Mittal C, Murad F. Activation of guanylate cyclase by superoxide dismutase and hydroxyl radical: a physiological regulator of guanosine 3′,5′-monophosphate formation. Proc Natl Acad Sci USA 1977; 74:4360–4364.PubMedCrossRefGoogle Scholar
  8. 8.
    Murad F, Mittal CK, Arnold WP et al. Guanylate cyclase: activation by azide, nitro compounds, nitric oxide, and hydroxyl radical and inhibition by hemoglobin and myoglobin. Adv Cyclic Nucleotide Res 1978; 9:145–157.PubMedGoogle Scholar
  9. 9.
    Gruetter CA, Barry B, McNamara DB et al. Relaxation of bovine coronary artery and activation of coronary arterial guanylate cyclase by nitric oxide, nitroprusside and a carcinogenic nitrosoamine. J Cyclic Nucleotide Res 1979; 5:211–224.PubMedGoogle Scholar
  10. 10.
    Ignarro LJ, Edwards JC, Gruetter DY et al. Possible involvement of S-nitrosothiols in the activation of guanylate cyclase by nitroso compounds. FEBS Lett 1980; 110:275–278.PubMedCrossRefGoogle Scholar
  11. 11.
    Ignarro LJ, Barry BK, Gruetter DY et al. Guanylate cyclase activation by nitroprusside and nitrosoguanidine is related to formation of S-nitrosothiol intermediates. Biochem Biophys Res Commun 1980; 94:93–100.PubMedCrossRefGoogle Scholar
  12. 12.
    Ignarro LJ, Gruetter CA. Requirement of thiols for activation of coronary arterial guanylate cyclase by glyceryl trinitrate and sodium nitrite. Possible involvement of S-nitrosothiols. Biochim Biophys Acta 1980; 631:221–231.PubMedGoogle Scholar
  13. 13.
    Feelisch M, Noack EA. Correlation between nitric oxide formation during degradation of organic nitrates and activation of guanylate cyclase. Eur J Pharmacol 1987; 139:19–30.PubMedCrossRefGoogle Scholar
  14. 14.
    Brüne B, Schmidt K-U, Ullrich V. Activation of soluble guanylate cyclase by carbon monoxide and inhibition by superoxide anion. Eur J Biochem 1990; 192:683–688.PubMedCrossRefGoogle Scholar
  15. 15.
    Utz J, Ullrich V. Carbon monoxide relaxes ileal smooth muscle through activation of guanylate cyclase. Biochem Pharmacol 1991; 41:1195–1201.PubMedCrossRefGoogle Scholar
  16. 16.
    Schmidt HHHW. NO, CO and OH. Endogenous soluble guanylyl cyclase-activating factors. FEBS Lett 1992; 307:102–107.PubMedCrossRefGoogle Scholar
  17. 17.
    Maines MD. Carbon monoxide: an emerging regulator of cGMP in the brain. Mol Cell Neurosci 1993; 4:389–397.PubMedCrossRefGoogle Scholar
  18. 18.
    Marks GS. Heme oxygenase: the physiological role of one of its metabolites, carbon monoxide and interactions with zinc protoporphyrin, cobalt protoporphyrin and other metalloporphyrins. Cell Mol Biol 1994; 40:863–870.PubMedGoogle Scholar
  19. 19.
    Stone JR, Sands RH, Dunham WR et al. Electron paramagnetic resonance spectral evidence for the formation of a penta-coordinated nitrosyl-heme complex on soluble guanylate cyclase. Biochem Biophys Res Commun 1995; 207:572–577.PubMedCrossRefGoogle Scholar
  20. 20.
    Stone JR, Marietta MA. Heme stoichiometry of heterodimeric soluble guanylate cyclase. Biochemistry 1995; 34:14668–14674.PubMedCrossRefGoogle Scholar
  21. 21.
    Stone JR, Marietta MA. The ferrous heme of soluble guanylate cyclase: formation of hexacoordinate complexes with carbon monoxide and nitrosomethane. Biochemistry 1995; 34:16397–16403.PubMedCrossRefGoogle Scholar
  22. 22.
    Verma A, Hirsch DJ, Glatt CE et al. Carbon monoxide: a putative neural messenger. Science 1993; 259:381–384.PubMedCrossRefGoogle Scholar
  23. 23.
    Vigne P, Feolde E, Ladoux A et al. Contributions of NO synthase and heme oxygenase to cGMP formation by cytokine and hemin treated brain capillary endothelial cells. Biochem Biophys Res Commun 1995; 214:1–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Wedel B, Humbert P, Harteneck C et al. Mutation of His-105 in the β1 subunit yields a nitric oxide-insensitive form of soluble guanylyl cyclase. Proc Natl Acad Sci USA 1994; 91:2592–2596.PubMedCrossRefGoogle Scholar
  25. 25.
    Gerzer R, Böhme E, Hofmann F et al. Soluble guanylate cyclase purified from bovine lung contains heme and copper. FEBS Lett 1981; 132:71–74.PubMedCrossRefGoogle Scholar
  26. 26.
    Stone JR, Marietta MA. Soluble guanylate cyclase from bovine lung: activation with nitric oxide and carbon monoxide and spectral characterization of the ferrous and ferric states. Biochemistry 1994; 33:5636–5640.PubMedCrossRefGoogle Scholar
  27. 27.
    Ignarro LJ, Wood KS, Wolin MS. Activation of purified soluble guanylate cyclase by protoporphyrin IX. Proc Natl Acad Sci USA 1982; 79:2870–2873.PubMedCrossRefGoogle Scholar
  28. 28.
    Wolin MS, Wood KS, Ignarro LJ. Guanylate cyclase from bovine lung. A kinetic analysis of the regulation of the purified soluble enzyme by protoporphyrin IX, heme, and nitrosyl-heme. J Biol Chem 1982; 257:13312–13320.PubMedGoogle Scholar
  29. 29.
    Ohlstein EH, Wood KS, Ignarro LJ. Purification and properties of heme-deficient hepatic soluble guanylate cyclase: effects of heme and other factors on enzyme activation by NO, NO-heme, and protoporphyrin IX. Arch Biochem Biophys 1982; 218:187–198.PubMedCrossRefGoogle Scholar
  30. 30.
    Ignarro LJ, Ballot B, Wood KS. Regulation of soluble guanylate cyclase activity by porphyrins and metalloporphyrins. J Biol Chem 1984; 259:6201–6207.PubMedGoogle Scholar
  31. 31.
    Ignarro LJ, Adams JB, Horwitz PM et al. Activation of soluble guanylate cyclase by NO-hemoproteins involves NO-heme exchange. Comparison of heme-containing and heme-deficient enzyme forms. J Biol Chem 1986; 261:4997–5002.PubMedGoogle Scholar
  32. 32.
    Mülsch A, Gerzer R. Purification of heme-containing soluble guanylyl cyclase. Methods Enzymol 1991; 195:377–383.PubMedCrossRefGoogle Scholar
  33. 33.
    DeRubertis FR, Craven PA, Pratt DW. Electron spin resonance study of the role of nitrosyl-heme in the activation of guanylate cyclase by nitrosoguanidine and related agonists. Biochem Biophys Res Commun 1978; 83:158–167.PubMedCrossRefGoogle Scholar
  34. 34.
    Craven PA, DeRubertis FR. Restoration of the responsiveness of purified guanylate cyclase to nitrosoguanidine, nitric oxide, and related activators by heme and hemoproteins. Evidence for involvement of the paramagnetic nitrosyl-heme complex in enzyme activation. J Biol Chem 1978; 253:8433–8443.PubMedGoogle Scholar
  35. 35.
    Craven PA, DeRubertis FR, Pratt DW. Electron spin resonance study of the role of NO-catalase in the activation of guanylate cyclase by NaN3 and NH2OH. Modulation of enzyme responses by heme proteins and their nitrosyl derivatives. J Biol Chem 1979; 254:8213–8222.PubMedGoogle Scholar
  36. 36.
    Traylor TG, Sharma VS. Why NO? Biochemistry 1992; 31:2847–2849.PubMedCrossRefGoogle Scholar
  37. 37.
    Traylor TG, Duprat AF, Sharma VS. Nitric oxide-triggered heme-mediated hydrolysis: a possible model for biological reactions of NO. J Am Chem Soc 1993; 115:810–811.CrossRefGoogle Scholar
  38. 38.
    Tsai A. How does NO activates heme-proteins? FEBS Lett 1994; 341:141–145.PubMedCrossRefGoogle Scholar
  39. 39.
    Yu AE, Hu S, Spiro TG et al. Resonance Raman spectroscopy of soluble guanylyl cyclase reveals displacement of distal and proximal heme ligands by NO. J Am Chem Soc 1994; 116:4117–4118.CrossRefGoogle Scholar
  40. 40.
    Stone JR, Sands RH, Dunham WR et al. Spectral and ligand-binding properties of an unusual hemoprotein, the ferric form of soluble guanylate cyclase. Biochemistry 1996; 35:3258–3262.PubMedCrossRefGoogle Scholar
  41. 41.
    Burstyn JN, Yu AE, Dierks EA et al. Studies of the heme coordination and ligand binding properties of soluble guanylyl cyclase (sGC): characterization of Fe(II)sGC and Fe(II)sGC(CO) by electronic absorption and magnetic circular dichroism spectroscopies and failure of CO to activate the enzyme. Biochemistry 1995; 34:5896–5903.PubMedCrossRefGoogle Scholar
  42. 42.
    Kharitonov VG, Sharma VS, Pilz RB et al. Basis of guanylate cyclase activation by carbon monoxyde. Proc Natl Acad Sci USA 1995; 92:2568–2571.PubMedCrossRefGoogle Scholar
  43. 43.
    Stone JR, Marietta MA. Spectral and kinetic studies on the activation of soluble guanylate cyclase by nitric oxide. Biochemistry 1996; 35:1093–1099.PubMedCrossRefGoogle Scholar
  44. 44.
    Kim Y-M, Bergonia HA, Müller C et al. Loss and degradation of enzyme-bound heme induced by cellular nitric oxide synthesis. J Biol Chem 1995; 270:5710–5713.PubMedCrossRefGoogle Scholar
  45. 45.
    Bonkale WL, Winblad B, Ravid R et al. Reduced nitric oxide responsive soluble guanylyl cyclase in the superior temporal cortex of patients with Alzheimer’s disease. Neurosci Lett 1995; 187:5–8.PubMedCrossRefGoogle Scholar
  46. 46.
    Hibbs JB, Taintor RR, Vavrin Z. Iron depletion: possible cause of tumor cell cytotoxicity induced by activated macrophages. Biochem Biophys Res Commun 1984; 123:716–723.PubMedCrossRefGoogle Scholar
  47. 47.
    Drapier J-C, Hibbs JB. Murine cytotoxic activated macrophages inhibit aconitase in tumor cells. Inhibition involves the iron-sulfur prosthetic group and is reversible. J Clin Invest 1986; 78:790–797.PubMedCrossRefGoogle Scholar
  48. 48.
    Stuehr DJ, Marietta MA. Induction of nitrite/nitrate synthesis in murine macrophages by BCG infection, lymphokines, or interferon-γ. J Immunol 1987; 139:518–525.PubMedGoogle Scholar
  49. 49.
    Hibbs JB, Vavrin Z, Taintor RR. L-arginine is required for expression of the activated macrophage effector mechanism causing selective metabolic inhibition in target cells. J Immunol 1987; 138:550–565.PubMedGoogle Scholar
  50. 50.
    Wharton M, Granger DL, Durack DT. Mitochondrial iron loss from leukemia cells injured by macrophages. A possible mechanism for electron transport chain defects. J Immunol 1988; 141:1311–1317.PubMedGoogle Scholar
  51. 51.
    Drapier J-C, Hibbs JB. Differentiation of murine macrophages to express nonspecific cytotoxicity for tumor cells results in L-arginine-dependent inhibition of mitochondrial iron-sulfur enzymes in the macrophage effector cells. J Immunol 1988; 140:2829–2838.PubMedGoogle Scholar
  52. 52.
    Drapier J-C, Wietzerbin J, Hibbs JB. Interferon gamma and tumor necrosis factor induce the L-arginine-dependent cytotoxic effector mechanism in murine macrophages. Eur J Immunol 1988; 18:1587–1592.PubMedCrossRefGoogle Scholar
  53. 53.
    Hibbs JB, Taintor RR, Vavrin Z et al. Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun 1988; 157:87–94.PubMedCrossRefGoogle Scholar
  54. 54.
    Hibbs JB, Taintor RR, Vavrin Z et al. Synthesis of nitric oxide from a terminal guanidino nitrogen atom of L-arginine: a molecular mechanism regulating cellular proliferation that targets intracellular iron. In: Moncada S and Higgs EA, eds. Nitric Oxide from L-Arginine: a Bioregulatory System. Amsterdam: Elsevier Science Publishers BV, 1990:189–223.Google Scholar
  55. 55.
    Participants in the 39th Forum in Immunology. L-arginine-derived nitric oxide and the cell-mediated immune response. Res Immunol 1991; 142:553–602.CrossRefGoogle Scholar
  56. 56.
    Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J 1992; 6:3051–3064.PubMedGoogle Scholar
  57. 57.
    Stuehr DJ, Griffith OW. Mammalian nitric oxide synthases. Adv Enzymol 1992; 65:287–346.PubMedGoogle Scholar
  58. 58.
    Hibbs Jr JB. Cytokine induced synthesis of nitric oxide from L-arginine: a cytotoxic mechanism that targets intracelluler iron. In: Riederer P and Youdim MBH, eds. Iron in Central Nervous System Disorders. Wien, New York: Springer-Verlag, 1993: 155–171.Google Scholar
  59. 59.
    Lepoivre M, Chenais B, Yapo A et al. Alterations of ribonucleotide reductase activity following induction of the nitrite-generating pathway in adenocarcinoma cells. J Biol Chem 1990; 265:14143–14149.PubMedGoogle Scholar
  60. 60.
    Kwon NS, Stuehr DJ, Nathan CF. Inhibition of tumor cell ribonucleotide reductase by macrophage-derived nitric oxide. J Exp Med 1991; 174:761–767.PubMedCrossRefGoogle Scholar
  61. 61.
    Lepoivre M, Flaman J-M, Henry Y. Early loss of the tyrosyl radical in ribonucleotide reductase of adenocarcinoma cells producing nitric oxide. J Biol Chem 1992; 267:22994–23000.PubMedGoogle Scholar
  62. 62.
    Lepoivre M, Flaman J-M, Bobé P et al. Quenching of the tyrosyl free radical of ribonucleotide reductase by nitric oxide. Relationship to cytostasis induced in tumor cells by cytotoxic macrophages. J Biol Chem 1994; 269:21891–21897.PubMedGoogle Scholar
  63. 63.
    Pellat C, Henry Y, Drapier J-C. IFN-γ-activated macrophages: detection by electron paramagnetic resonance of complexes between L-arginine-derived nitric oxide and non-heme iron proteins. Biochem Biophys Res Commun 1990; 166:119–125.PubMedCrossRefGoogle Scholar
  64. 64.
    Pellat C, Henry Y, Drapier J-C. Detection by electron paramagnetic resonance of a nitrosyl-iron-type signal in interferon-γ-activated macrophages. In: Moncada S and Higgs EA, eds. Nitric Oxide from L-Arginine: a Bioregulatory System. Amsterdam, Elsevier Science Publishers BV, 1990: 281–289.Google Scholar
  65. 65.
    Lancaster JR, Hibbs JB. EPR demonstration of iron-nitrosyl complex formation by cytotoxic activated macrophages. Proc Natl Acad Sci USA 1990; 87:1223–1227.PubMedCrossRefGoogle Scholar
  66. 66.
    Henry Y, Ducrocq C, Drapier J-C et al. Nitric oxide, a biological effector. Electron paramagnetic resonance detection of nitro-syl-iron-protein complexes in whole cells. Eur Biophys J 1991; 20:1–15.PubMedCrossRefGoogle Scholar
  67. 67.
    Beinert H, Kennedy MC. Engineering of protein bound iron-sulfur clusters. A tool for the study of protein and cluster chemistry and mechanism of iron-sulfur enzymes. Eur J Biochem 1989; 186:5–15.PubMedCrossRefGoogle Scholar
  68. 68.
    Beinert H. Recent developments in the field of iron-sulfur proteins. FASEB J 1990; 4:2483–2491.PubMedGoogle Scholar
  69. 69.
    Drapier J-C, Pellat C, Henry Y Generation of EPR-detectable nitrosyl-iron complexes in tumor target cells cocultured with activated macrophages. J Biol Chem 1991; 266:10162–10167.PubMedGoogle Scholar
  70. 70.
    Drapier J-C, Pellat C, Henry Y. Characterization of the nitrosyl-iron complexes generated in tumour cells after co-culture with activated macrophages. In: Moncada S, Marietta MA, Hibbs JB et al, eds. The Biology of Nitric Oxide. London, UK: Portland Press, 1992:72–76.Google Scholar
  71. 71.
    Pellat C, Henry Y, Drapier J-C. Detection of nitrosyl-iron complexes in tumor target cells after coculture with activated macrophages. In: Melzer MS and Mantovani A, eds. Cellular and Cytokine Networks in Tissue Immunity. Wiley-Liss, 1991:229–234.Google Scholar
  72. 72.
    Henry Y, Lepoivre M, Drapier J-C et al. EPR characterisation of molecular targets for NO in mammalian cells and organelles. FASEB J 1993; 7:1124–1134.PubMedGoogle Scholar
  73. 73.
    Geng YJ, Hellstrand K, Wennmalm Å et al. Apoptotic death of human leukemic cells induced by vascular cells expressing nitric oxide synthase in response to γ-interferon and tumor necrosis factor-a. Cancer Res 1996; 56:866–874.PubMedGoogle Scholar
  74. 74.
    Vanin AF, Men’shikov GB, Moroz IA et al. The source of non-heme iron that binds nitric oxide in cultivated macrophages. Biochim Biophys Acta 1992; 1135:275–279.PubMedCrossRefGoogle Scholar
  75. 75.
    Vanin AF, Mordvintcev PI, Hauschildt S et al. The relationship between L-arginine-dependent nitric oxide synthesis, nitrite release and dinitrosyl-iron complex formation by activated macrophages. Biochim Biophys Acta 1993; 1177:37–42.PubMedCrossRefGoogle Scholar
  76. 76.
    Cooper CE, Brown GC. The interactions between nitric oxide and brain nerve terminals as studied by electron paramagnetic resonance. Biochem Biophys Res Commun 1995; 212:404–412.PubMedCrossRefGoogle Scholar
  77. 77.
    McDonald CC, Phillips WD, Mower HF. An electron spin resonance of some complexes of iron, nitric oxide, and anionic ligands. J Am Chem Soc 1965; 87:3319–3326.CrossRefGoogle Scholar
  78. 78.
    Woolum JC, Tiezzi E, Commoner B. Electron spin resonance of iron-nitric oxide complexes with amino acids, peptides and proteins. Biochim Biophys Acta 1968; 160:311–320.PubMedGoogle Scholar
  79. 79.
    Woolum J, Commoner B. Isolation and identification of a paramagnetic complex from the livers of carcinogen-treated rats. Biochim Biophys Acta 1970; 201:131–140.PubMedGoogle Scholar
  80. 80.
    Salerno JC, Ohnishi T, Lim J et al. Tetranuclear and binuclear iron-sulfur clusters in succinate dehydrogenase: a method of iron quantitation by formation of paramagnetic complexes. Biochem Biophys Res Commun 1976; 73:833–840.PubMedCrossRefGoogle Scholar
  81. 81.
    Meyer J. Comparison of carbon monoxide, nitric oxide, and nitrite as inhibitors of the nitrogenase from Clostridium pasteurianum. Arch Biochem Biophys 1981; 210:246–256.PubMedCrossRefGoogle Scholar
  82. 82.
    Reddy D, Lancaster JR, Cornforth DP. Nitrite inhibition of Clostridium botulinum: electron spin resonance detection of iron-nitric oxide complexes. Science 1983; 221:769–770.PubMedCrossRefGoogle Scholar
  83. 83.
    Michalski WP, Nicholas DJD. Inhibition of nitrogenase by nitrite and nitric oxide in Rhodopseudomonas sphaeroides f. sp. denitrificans. Arch Microbiol 1987; 147:304–308.CrossRefGoogle Scholar
  84. 84.
    Butler AR, Glidewell C, Li M-H. Nitrosyl complexes of iron-sulfur clusters. Adv Inorg Chem 1988; 32:335–393.CrossRefGoogle Scholar
  85. 85.
    Payne MJ, Glidewell C, Cammack. Interactions of iron-thiol-nitrosyl compounds with the phophoroclastic system of Clostridium sporogenes. J Gen Microbiol 1990; 136:2077–2087.PubMedGoogle Scholar
  86. 86.
    Hyman MR, Seefeldt LC, Morgan TV et al. Kinetic and spectroscopic analysis of the inactivating effects of nitric oxide on the individual components of Azotobacter vinelandii nitrogenase. Biochemistry 1992; 31:2947–2955.PubMedCrossRefGoogle Scholar
  87. 87.
    Calmels S, Ohshima H, Henry Y et al. Characterization of bacterial cytochrome cd1-nitrite reductase as one enzyme responsible for catalysis of nitrosation of secondary amines. Carcinogenesis 1996; 17:533–536.PubMedCrossRefGoogle Scholar
  88. 88.
    Kennedy MC, Gan T, Antholine WE et al. Metallothionein reacts with Fe2+ and NO to form products with g = 2.039 ESR signal. Biochem Biophys Res Commun 1993; 196:632–635.PubMedCrossRefGoogle Scholar
  89. 89.
    Lee M, Arosio P, Cozzi A et al. Identification of the EPR-active iron-nitrosyl complexes in mammalian ferritins. Biochemistry 1994; 33:3679–3687.PubMedCrossRefGoogle Scholar
  90. 90.
    Hausladen A, Fridovich I. Superoxide and peroxy ni trite inactivate aconitases, but nitric oxide does not. J Biol Chem 1994; 269:29405–29408.PubMedGoogle Scholar
  91. 91.
    Castro L, Rodriguez M, Radi R. Aconitase is readily inactivated by peroxynitrite, but not by its precursor, nitric oxide. J Biol Chem 1994; 269:29409–29415.PubMedGoogle Scholar
  92. 92.
    Keller R, Keist R, Klauser S et al. The macrophage response to bacteria: flow of L-arginine through the nitric oxide and urea pathways and induction of tumoricidal activity. Biochem Biophys Res Commun 1991; 177:821–827.PubMedCrossRefGoogle Scholar
  93. 93.
    Corbett JA, Lancaster JR, Sweetland MA et al. Interleukin-lβ-induced formation of EPR-detectable iron-nitrosyl complexes in islets of Langerhans. J Biol Chem 1991; 266:21351–21354.PubMedGoogle Scholar
  94. 94.
    Corbett JA, Wang JL, Hughes JH et al. Nitric oxide and cyclic GMP formation induced by interleukin 1β in islets of Langerhans. Evidence for an effector role of nitric oxide in islet dysfunction. Biochem J 1992; 229–235.Google Scholar
  95. 95.
    Corbett JA, Wang JL, Sweetland MA et al. Interleukin lβ induces the formation of nitric oxide by β-cells purified from rodent islets of Langerhans. Evidence for the β-cell as a source and site of action of nitric oxide. J Clin Invest 1992; 90:2384–2391.PubMedCrossRefGoogle Scholar
  96. 96.
    Corbett JA, Sweetland MA, Wang JL et al. Nitric oxide mediates cytokine-induced inhibition of insulin secretion by human islets of Langerhans. Proc Natl Acad Sci USA 1993; 90:1731–1735.PubMedCrossRefGoogle Scholar
  97. 97.
    Nussler AK, Geller DA, Sweetland MA et al. Induction of nitric oxide synthesis and its reactions in cultured human and rat hepatocytes stimulated with cytokines plus LPS. Biochem Biophys Res Commun 1993; 194:826–835.PubMedCrossRefGoogle Scholar
  98. 98.
    Stadler J, Bergonia HA, Di Silvio M et al. Nonheme iron-nitrosyl complex formation in rat hepatocytes: detection by electron paramagnetic resonance spectroscopy. Arch Biochem Biophys 1993; 302:4–11.PubMedCrossRefGoogle Scholar
  99. 99.
    Nussler AK, Di Silvio M, Liu Z et al. Further characterization and comparison of inducible nitric oxide synthase in mouse, rat, and human hepatocytes. Hepatology 1995; 21:1552–1560.PubMedGoogle Scholar
  100. 100.
    Lancaster JR, Werner-Felmayer G, Wachter H. Coinduction of nitric oxide synthesis and intracellular nonheme iron-nitrosyl complexes in murine cytokine-treated fibroblasts. Free Rad Biol Med 1994; 16:869–870.PubMedCrossRefGoogle Scholar
  101. 101.
    Geng YJ, Petersson AS, Wennmalm Å et al. Cytokine-induced expression of nitric oxide synthase results in nitrosylation of heme and nonheme iron proteins in vascular smooth muscle cells. Exp Cell Res 1994; 214:418–428.PubMedCrossRefGoogle Scholar
  102. 102.
    Mülsch A, Mordvintcev P, Vanin AF et al. Formation and release of dinitrosyl iron complexes by endothelial cells. Biochem Biophys Res Commun 1993; 196:1303–1308.PubMedCrossRefGoogle Scholar
  103. 103.
    Stubbe J. Ribonucleotide reductases. Adv Enzymol 1990; 63:349–419.PubMedGoogle Scholar
  104. 104.
    Fontecave M, Nordlund P, Eklund H et al. The redox centers of ribonucleotide reductase of Escherichia coli. Adv Enzymol 1992; 65:147–183.PubMedGoogle Scholar
  105. 105.
    Reichard P. From RNA to DNA, why so many ribonucleotide reductases? Science 1993; 260:1773–1777.PubMedCrossRefGoogle Scholar
  106. 106.
    Lepoivre M, Fieschi F, Coves J et al. Inactivation of ribonucleotide reductase by nitric oxide. Biochem Biophys Res Commun 1991; 179:442–448.PubMedCrossRefGoogle Scholar
  107. 107.
    Lepoivre M, Fieschi F, Coves J et al. Inhibition of ribonucleotide reductase by nitric oxide donors. In: Moncada S, Marietta MA, Hibbs J et al, eds. The biology of nitric oxide. London, UK: Portland Press, 1992: 95–98.Google Scholar
  108. 108.
    Lepoivre M, Boudbid H, Petit JF. Antiproliferative activity of γ-interferon combined with lipopolysaccharide on murine adenocarcinoma: dependence on an L-arginine metabolism with production of nitrite and citrulline. Cancer Res 1989; 49:1970–1976.PubMedGoogle Scholar
  109. 109.
    Lepoivre M, Bobé P, Henry Y. Reversible alteration of ribonucleotide reductase E.P.R. properties in tumor target cells cocultured with NO-producing macrophages. In: Moncada S, Feelisch M, Busse R, Higgs EA, eds. The Biology of Nitric Oxide, Vol 4. London, UK, Portland Press, 1994:186–189.Google Scholar
  110. 110.
    Roy B, Lepoivre M, Henry Y et al. Inhibition of ribonucleotide reductase by nitric oxide derived from thionitrites: reversible modifications of both subunits. Biochemistry 1995; 34:5411–5418.PubMedCrossRefGoogle Scholar
  111. 111.
    Haskin CJ, Ravi N, Lynch JB et al. Reaction of NO with the reduced R2 protein of ribonucleotide reductase from Escherichia coli. Biochemistry 1995; 34:11090–11098.PubMedCrossRefGoogle Scholar
  112. 112.
    Roy B, Du Moulinet d’Hardemare A, Fontecave M. New thionitrites: synthesis, stability, and nitric oxide generation. J Org Chem 1994; 59:7019–7026.CrossRefGoogle Scholar
  113. 113.
    Szekeres T, Gharehbaghi K, Fritzer M et al. Biochemical and antitumor activity of trimidox, a new inhibitor of ribonucleotide reductase. Cancer Chemother Pharmacol 1994; 34:63–66.PubMedCrossRefGoogle Scholar
  114. 114.
    Szekeres T, Vielnascher E, Novotny L et al. Iron binding capacity of trimidox (3,4,5-trihydroxybenzamidoxime), a new inhibitor of the enzyme ribonucleotide reductase. Eur J Clin Chem Clin Biochem 1995; 33:785–789.PubMedGoogle Scholar
  115. 115.
    Ponka P, Schulman HM, Woodworth RC. Iron Transport and Storage. Boca Raton, USA: CRC Press, 1990.Google Scholar
  116. 116.
    Crichton RR, Charloteaux-Wauters M. Iron transport and storage. Eur J Biochem 1987; 164:485–506.PubMedCrossRefGoogle Scholar
  117. 117.
    Crichton RR, Ward RJ. Iron metabolism — New perspectives in view. Biochemistry 1992; 24:11255–11264.CrossRefGoogle Scholar
  118. 118.
    Klausner RD, Rouault TA. A double life: cytosolic aconitase as a regulatory RNA binding protein. Mol Biol Cell 1993; 4:1–5.PubMedGoogle Scholar
  119. 119.
    Klausner RD, Rouault TA, Harford JB. Regulating the fate of mRNA: the control of cellular iron metabolism. Cell 1993; 72:19–28.PubMedCrossRefGoogle Scholar
  120. 120.
    Lazo JS, Pitt BR. Metallothioneins and cell death by anticancer drugs. Annu Rev Pharmacol Toxicol 1995; 35:635–653.PubMedCrossRefGoogle Scholar
  121. 121.
    Pauwels M, Van Weyenbergh J, Soumillion A et al. Induction by zinc of specific metallothionein isoforms in human monocytes. Eur J Biochem 1994; 220:105–110.PubMedCrossRefGoogle Scholar
  122. 122.
    Takeda K, Fujita H, Shibahara S. Differential control of the metal-mediated activation of the human heme oxygenase-1 and metallothionein IIA genes. Biochem Biophys Res Commun 1995; 207:160–167.PubMedCrossRefGoogle Scholar
  123. 123.
    Yu X, Wu Z, Fenselau C. Covalent sequestration of melphalan by metallothionein and selective alkylation of cysteines. Biochemistry 1995; 34:3377–3385.PubMedCrossRefGoogle Scholar
  124. 124.
    Schwarz MA, Lazo JS, Yalowich JC et al. Cytoplasmic metallothionein overexpression protects NIH 3T3 cells from tert-buty hydroperoxide toxicity. J Biol Chem 1994; 269:15238–15243.PubMedGoogle Scholar
  125. 125.
    Shibuya K, Satoh M, Muraoka M et al. Induction of metallothionein synthesis in transplanted murine tumors by X irradiation. Radiat Res 1995; 143:54–57.PubMedCrossRefGoogle Scholar
  126. 126.
    Choudhuri S, McKim JM, Klaassen CD. Induction of metallothionein by superantigenic bacterial exotoxin: probable involvement of the immune system. Biochim Biophys Acta 1994; 1225:171–179.PubMedGoogle Scholar
  127. 127.
    Sato M, Sasaki M, Hojo H. Differential induction of metallothionein synthesis by interleukin-6 and tumor necrosis factor-α in rat tissues. Int J Immunopharmac 1994; 16:187–195.CrossRefGoogle Scholar
  128. 128.
    Sato M, Sasaki M, Hojo H. Antioxidative roles of metallothionein and manganese superoxide dismutase induced by tumor necrosis factor-a and interleukin-6. Arch Biochem Biophys 1995; 316:738–744.PubMedCrossRefGoogle Scholar
  129. 129.
    Stennard FA, Holloway AF, Hamilton J et al. Characterization of six additional human metallothionein genes. Biochim Biophys Acta 1994; 1218:357–365.PubMedGoogle Scholar
  130. 130.
    Goulding H, Jasani B, Pereira H et al. Metallothionein expression in human breast cancer. Br J Cancer 1995; 72:968–972.PubMedCrossRefGoogle Scholar
  131. 131.
    Nagel WW, Vallee BL. Cell cycle regulation of metallothionein in human colonic cancer cells. Proc Natl Acad Sci USA 1995; 92:579–583.PubMedCrossRefGoogle Scholar
  132. 132.
    Otsuka F, Iwamatsu A, Suzuki K et al. Purification and characterization of a protein that binds to metal responsive elements of the human metallothionein IIA gene. J Biol Chem 1994; 269:23700–23707.PubMedGoogle Scholar
  133. 133.
    Zeng J, Heuchel R, Schaffner W et al. Thionein (apometallothionein) can modulate DNA binding and transcription activation by zinc finger containing factor Sp1. FEBS Lett 1991; 279:310–312.PubMedCrossRefGoogle Scholar
  134. 134.
    Zeng J, Vallee BL, Kägi JHR. Zinc transfer from transcription factor IIIA fingers to thionein clusters. Proc Natl Acad Sci USA 1991; 88:9984–9988.PubMedCrossRefGoogle Scholar
  135. 135.
    Schwarz MA, Lazo JS, Yalowich JC et al. Metallothionein protects against the cytotoxic and DNA-damaging effects of nitric oxide. Proc Natl Acad Sci USA 1995; 92:4452–4456.PubMedCrossRefGoogle Scholar
  136. 136.
    Kröncke K-D, Fehsel K, Schmidt T et al. Nitric oxide destroys zinc-sulfur clusters inducing zinc release from metallothionein and inhibition of the zinc finger-type yeast transcription activator Lac9. Biochem Biophys Res Commun 1994; 200:1105–1110.PubMedCrossRefGoogle Scholar
  137. 137.
    Chasteen ND, Woodworth RC. Transferrin and lactoferrin. In: Ponka P, Schulman HM, Woodworth RC, eds. Iron Transport and Storage. Boca Raton, USA: CRC Press, 1990: 67–79.Google Scholar
  138. 138.
    Schlabach MR, Bates GW. The synergistic binding of anions and Fe3+ by transferrin. Implications for the interlocking sites hypothesis. J Biol Chem 1975; 250:2182–2188.PubMedGoogle Scholar
  139. 139.
    Bailey S, Evans RW, Garratt RC et al. Molecular structure of serum transferrin at 3.3 Å resolution. Biochemistry 1988; 27:5804–5812.PubMedCrossRefGoogle Scholar
  140. 140.
    Anderson BF, Baker HM, Norris GE et al. Structure of human lactoferrin: crystallo-graphic structure analysis and refinement at 2.8 Å resolution. J Mol Biol 1989; 209:711–734.PubMedCrossRefGoogle Scholar
  141. 141.
    Anderson BF, Baker HM, Norris GE et al. Apolactoferrin structure demonstrates ligand-induced conformational change in transferrins. Nature 1990; 344:784–787.PubMedCrossRefGoogle Scholar
  142. 142.
    Smith CA, Anderson BF, Baker HM et al. Metal substitution in transferrins: the crystal structure of human copper-lactoferrin at 2.1 Å resolution. Biochemistry 1992; 31:4527–4533.PubMedCrossRefGoogle Scholar
  143. 143.
    Harris DC, Rinehart AL, Hereld D et al. Reduction potential of iron in transferrin. Biochim Biophys Acta 1985; 838:295–301.PubMedGoogle Scholar
  144. 144.
    Bakoy OE, Thorstensen K. The process of cellular uptake of iron from transferrin. A computer simulation program. Eur J Biochem 1994; 222:105–122.PubMedCrossRefGoogle Scholar
  145. 145.
    Harris WR, Chen Y. Electron paramagnetic resonance and difference ultraviolet studies of Mn2+ binding to serum transferrin. J Inorg Biochem 1994; 54:1–19.PubMedCrossRefGoogle Scholar
  146. 146.
    Kubal G, Mason AB, Patel SU et al. Oxalate- and Ga3+-induced structural changes in human serum transferrin and its recombinant N-lobe. 1H NMR detection of preferential C-lobe Ga3+ binding. Biochemistry 1993; 32:3387–3395.PubMedCrossRefGoogle Scholar
  147. 147.
    Aramini JM, Vogel HJ. A scandium-45 NMR study of ovotransferrin and its half-molecules. J Am Chem Soc 1994; 116:1988–1993.CrossRefGoogle Scholar
  148. 148.
    Aramini JM, Krygsman PH, Vogel HJ. Thallium-205 and carbon-13 NMR studies of human sero- and chicken ovotransferrin. Biochemistry 1994; 33:3304–3311.PubMedCrossRefGoogle Scholar
  149. 149.
    Scidel A, Bill E, Häggström L et al. Complementary Mössbauer and EPR studies of iron(III) in diferric human serum transferrin with oxalate or bicarbonate as synergistic anions. Arch Biochem Biophys 1994; 308:52–63.CrossRefGoogle Scholar
  150. 150.
    Grady JK, Mason AB, Woodworth RC et al. The effect of salt and site-directed mutations on the iron(III)-binding site of human serum transferrin as probed by EPR spectroscopy. Biochem J 1995; 309:403–410.PubMedGoogle Scholar
  151. 151.
    Dubach J, Gaffney BJ, More K et al. Effect of the synergistic anion on electron paramagnetic resonance spectra of iron-transfer-rin anion complexes is consistent with bidendate binding of the anion. Biophys J 1991; 59:1091–1100.PubMedCrossRefGoogle Scholar
  152. 152.
    Battistuzzi G, Sola M. Fe3+ binding to ovotransferrin in the presence of α-amino acids. Biochim Biophys Acta 1992; 1118:313–317.PubMedCrossRefGoogle Scholar
  153. 153.
    Vanin AF. Identification of divalent iron complexes with cysteine in biological systems by the EPR method. Biokhimia 1967; 32:228–232 (English translation 228–232).Google Scholar
  154. 154.
    Jezowska-Trezebiatowska B, Jezierski A. Electron spin resonance spectroscopy of iron nitrosyl complexes with organic ligands. J Molec Struct 1973; 19:635–640.CrossRefGoogle Scholar
  155. 155.
    Carmichael AJ, Steel-Goodwin L, Gray B et al. Nitric oxide interaction with lactoferrin and its production by macrophage cells studied by EPR and spin trapping. Free Rad Res Comms 1993; 19.S201–209.CrossRefGoogle Scholar
  156. 156.
    Richardson DR, Neumannova V, Ponka P. Nitrogen monoxide decreases iron uptake from transferrin but does not mobilise iron from prelabelled neoplastic cells. Biochim Biophys Acta 1995; 1266:250–260.PubMedCrossRefGoogle Scholar
  157. 157.
    Richardson DR, Neumannova V, Nagy E et al. The effect of redox-related species of nitrogen monoxide on transferrin and iron uptake and cellular proliferation of erythroleukemia (K562) cells. Blood 1995; 86:3211–3219.PubMedGoogle Scholar
  158. 158.
    Takenaka K, Suzuki S, Sakai N et al. Transferrin induces nitric oxide synthase mRNA in rat cultured aortic smooth muscle cells. Biochem Biophys Res Commun 1995; 213:608–615.PubMedCrossRefGoogle Scholar
  159. 159.
    159- LeBrun NE, Cheesman RM, Thomson AJ et al. An EPR investigation of non-haem iron sites in Escherichia coli bacterioferritin and their interaction with phosphate. A study using nitric oxide as a spin probe. FEBS Lett 1993; 323:261–266.CrossRefGoogle Scholar
  160. 160.
    LeBrun NE, Wilson MT, Andrews SC et al. Kinetic and structural characterization of an intermediate in the biomineralization of bacterioferritin. FEBS Lett 1993; 333:197–202.CrossRefGoogle Scholar
  161. 161.
    Watt GD, Frankel RB, Papaefthymiou GC. Reduction of mammalian ferritin. Proc Natl Acad Sci USA 1985; 82:3640–3643.PubMedCrossRefGoogle Scholar
  162. 162.
    Bolann BJ, Ulvik RJ. On the limited ability of superoxide to release iron from ferritin. Eur J Biochem 1990; 193:899–904.PubMedCrossRefGoogle Scholar
  163. 163.
    Bolann BJ, Ulvik RJ. Decay of superoxide catalyzed by ferritin. FEBS Lett 1993; 318:149–152.PubMedCrossRefGoogle Scholar
  164. 164.
    Monteiro HP, Vile GF, Winterbourn CC. Release of iron from ferritin by semiquinone, anthracycline, bipyridyl, and nitroaromatic radicals. Free Rad Biol Med 1989; 6:587–591.PubMedCrossRefGoogle Scholar
  165. 165.
    Moreno JJ, Foroozesh M, Church DF et al. Release of iron from ferritin by aqueous extracts of cigarette smoke. Chem Res Toxicol 1992; 5:116–123.PubMedCrossRefGoogle Scholar
  166. 166.
    Reif DW. Ferritin as a source of iron for oxidative damage. Free Rad Biol Med 1992; 12:417–427.PubMedCrossRefGoogle Scholar
  167. 167.
    Reif DW, Simmons RD. Nitric oxide mediates iron release from ferritin. Arch Biochem Biophys 1990; 283:537–541.PubMedCrossRefGoogle Scholar
  168. 168.
    Laulhère JP, Fontecave M. Nitric oxide does not promote iron release from ferritin. BioMetals 1996; 9:10–14.Google Scholar
  169. 169.
    Oria R, Sanchez L, Houston T et al. Effect of nitric oxide on expression of transferrin receptor and ferritin and on cellular iron metabolism in K562 human eryth-roleukemia cells. Blood 1995; 85:2962–2966.PubMedGoogle Scholar
  170. 170.
    Kim Y-M, Bergonia HA, Lancaster JR. Nitrogen oxide-induced autoprotection in isolated rat hepatocytes. FEBS Lett 1995; 374:228–232.PubMedCrossRefGoogle Scholar
  171. 171.
    Balla G, Jacob HS, Balla J et al. Ferritin: a cytoprotective antioxidant stratagem of endothelium. J Biol Chem 1992; 267:18148–18153.PubMedGoogle Scholar
  172. 172.
    Theil EC. Iron regulatory elements (IREs): a family of mRNA non-coding sequences. Biochem J 1994; 304:1–11.PubMedGoogle Scholar
  173. 173.
    Melefors Ö, Hentze MW. Iron regulatory factor — the conductor of cellular iron regulation. Blood Reviews 1993; 7:251–258.PubMedCrossRefGoogle Scholar
  174. 174.
    Haile DJ, Rouault TA, Tang CK et al. Reciprocal control of RNA-binding and aconitase activity in the regulation of the iron-responsive element binding protein: role of the iron-sulfur cluster. Proc Natl Acad Sci USA 1992; 89:7536–7540.PubMedCrossRefGoogle Scholar
  175. 175.
    Haile DJ, Rouault TA, Harford JB et al. Cellular regulation of the iron-responsive element binding protein: disassembly of the cubane iron-sulfur cluster results in high-affinity RNA binding. Proc Natl Acad Sci USA 1992; 89:11735–11739.PubMedCrossRefGoogle Scholar
  176. 176.
    Kennedy MC, Mende-Mueller L, Blondin GA et al. Purification and characterization of cytosolic aconitase from beef liver and its relationship to the iron-responsive element binding protein. Proc Natl Acad Sci USA 1992; 89:11730–11734.PubMedCrossRefGoogle Scholar
  177. 177.
    Basilion JP, Rouault TA, Massinople CM et al. The iron-responsive element-binding protein: localization of the RNA-binding site to the aconitase active-site cleft. Proc Natl Acad Sci USA 1994; 91:574–578.PubMedCrossRefGoogle Scholar
  178. 178.
    Hiding H, Henderson BR, Kühn LC. Mutational analysis of the [4Fe-4S]-cluster converting iron regulatory factor from its RNA-binding form to cytoplasmic aconitase. EMBO J 1994; 13:453–461.Google Scholar
  179. 179.
    Philpott CC, Klausner RD, Rouault TA. The bifunctional iron-responsive element binding protein/cytosolic aconitase: the role of active-site residues in ligand binding and regulation. Proc Natl Acad Sci USA 1994; 91:7321–7325.PubMedCrossRefGoogle Scholar
  180. 180.
    Ward RJ, Kühn LC, Kaldy P et al. Control of cellular iron homeostasis by iron-responsive elements in vivo. Eur J Biochem 1994; 220:927–931.PubMedCrossRefGoogle Scholar
  181. 181.
    Drapier J-C, Hiding H, Wietzerbin J et al. Biosynthesis of nitric oxide activates iron regulatory factor in macrophages. EMBO J 1993; 12:3643–3649.PubMedGoogle Scholar
  182. 182.
    Drapier J-C, Hirling H, Bouton C et al. Evidence that nitric oxide modulates IRP activities by targetting its [Fe-S] cluster. J Inorg Chem 1994; 56:44.Google Scholar
  183. 183.
    Weiss G, Goossen B, Doppler W et al. Translational regulation via iron-responsive elements by the nitric oxide/NO-synthase pathway. EMBO J 1993; 12:3651–3657.PubMedGoogle Scholar
  184. 184.
    Bouton C, Raveau M, Drapier J-C. Modulation of iron regulatory protein functions. Further insights into the role of nitrogen-and oxygen-derived reactive species. J Biol Chem 1996; 271:2300–2306.PubMedCrossRefGoogle Scholar
  185. 185.
    Drapier J-C, Bouton C. Modulation by nitric oxide of metalloprotein regulatory activities. BioEssays 1996, 18:549–556.PubMedCrossRefGoogle Scholar
  186. 186.
    Weiss G, Werner-Felmayer G, Werner ER et al. Iron regulates nitric oxide synthase activity by controlling nuclear transcription. J Exp Med 1994; 180:969–976.PubMedCrossRefGoogle Scholar
  187. 187.
    Pantopoulos K, Hentze MW. Nitric oxide signaling to iron-regulatory protein: direct control of ferritin mRNA translation and transferrin receptor mRNA stability in transfected fibroblasts. Proc Natl Acad Sci USA 1995; 92:1267–1271.PubMedCrossRefGoogle Scholar
  188. 188.
    Cairo G, Pietrangelo A. Nitric oxide-mediated activation of iron-regulatory protein controls hepatic iron metabolism during acute inflammation. Eur J Biochem 1995; 232:358–363.PubMedCrossRefGoogle Scholar
  189. 189.
    Jaffrey SR, Cohen NA, Rouault TA et al. The iron-responsve element binding protein: a target for synaptic actions of nitric oxide. Proc Natl Acad Sci USA 1994; 91:12994–12998.PubMedCrossRefGoogle Scholar
  190. 190.
    Ferreira GC, Franco R, Lloyd SG et al. Structure and function of ferrochelatase. J Bioenerg Biomembr 1995; 27:221–229.PubMedCrossRefGoogle Scholar
  191. 191.
    Dailey HA, Finnegan MG, Johnson MK. Human ferrochelatase is an iron-sulfur protein. Biochemistry 1994; 33:403–407.PubMedCrossRefGoogle Scholar
  192. 192.
    Ferreira GC. Mammalian ferrochelatase. Overexpression in Escherichia coli as a soluble protein, purification and characterization. J Biol Chem 1994; 269:4396–4400.PubMedGoogle Scholar
  193. 193.
    Ferreira GC, Franco R, Lloyd SG et al. Mammalian ferrochelatase, a new addition to the metalloenzyme family. J Biol Chem 1994; 269:7062–7065.PubMedGoogle Scholar
  194. 194.
    Franco R, Moura JJG, Moura I et al. Characterization of the iron-binding site in mammalian ferrochelatase by kinetic and Mössbauer methods. J Biol Chem 1995; 270:26352–26357.PubMedCrossRefGoogle Scholar
  195. 195.
    Ferreira GC. Ferrochelatase binds the iron-responsive element present in the erythroid 5-aminolevulinate mRNA. Biochem Biophys Res Commun 1995; 214:875–878.PubMedCrossRefGoogle Scholar
  196. 196.
    Furukawa T, Kohno H, Tokunaga R et al. Nitric oxide-mediated inactivation of mammalian ferrochelatase in vivo and in vitro: possible involvement of the iron-sulphur cluster of the enzyme. Biochem J 1995; 310:533–538.PubMedGoogle Scholar
  197. 197.
    Sellers VM, Johnson MK, Dailey HA. Function of the [2Fe-2S] cluster in mammalian ferrochelatase: a possible role as a nitric oxide sensor. Biochemistry 1996; 35:2699–2704.PubMedCrossRefGoogle Scholar
  198. 198.
    Hidalgo E, Demple B. An iron-sulfur center essential for transcriptional activation by the redox-sensing SoxR protein. EMBO J 1994; 13:138–146.PubMedGoogle Scholar
  199. 199.
    Hidalgo E, Bollinger JM, Bradley TM et al. Binuclear [2Fe-2S] clusters in the Escherichia coli SoxR protein and role of the metal centers in transcription. J Biol Chem 1995; 270:20908–20914.PubMedCrossRefGoogle Scholar
  200. 200.
    Nunoshiba T, DeRojas-Walker T, Wishnok JS et al. Activation by nitric oxide of an oxidative-stress response that defends Escherichia coli against activated macrophages. Proc Natl Acad Sci USA 1993; 90:9993–9997.PubMedCrossRefGoogle Scholar
  201. 201.
    Cunningham RP, Asahara H, Bank JF et al. Endonuclease III is an iron-sulfur protein. Biochemistry 1989; 28:4450–4455.PubMedCrossRefGoogle Scholar
  202. 202.
    Pantopoulos K, Hentze MW. Rapid responses to oxidative stress mediated by iron regulatory protein. EMBO J 1995; 14:2917–2924.PubMedGoogle Scholar
  203. 203.
    Juckett MB, Weber M, Balla J et al. Nitric oxide donors modulate ferritin and protect endothelium from oxidative injury. Free Rad Biol Med 1996; 20:63–73.PubMedCrossRefGoogle Scholar
  204. 204.
    Henry YA, Singel DJ. Metal-nitrosyl interactions in nitric oxide biology probed by electron paramagnetic resonance spectroscopy. In: Feelisch M, Stamler JS, eds. Methods in Nitric Oxide Research. John Wiley & Sons, 1996:357–372.Google Scholar

Copyright information

© R.G. Landes Company 1997

Authors and Affiliations

  • Yann A. Henry
  • Béatrice Ducastel
  • Annie Guissani

There are no affiliations available

Personalised recommendations