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Hypoxia pp 249-272 | Cite as

The heme oxygenase system and cellular defense mechanisms

Do HO-1 and HO-2 have different functions?
  • Mahin D. Maines
  • Nariman Panahian
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 502)

Abstract

Heme oxygenase isozymes, HO-1, HO-2 and HO-3, are HSP32 protein cognates, with a known function of catalyzing the isomer specific oxidation of the heme molecule, including that of NO synthase. Unknown until recent years was that the system is a central component of the cellular defense mechanisms; this can be attributed to a combination of many factors. In biological systems HO activity is responsible for production of equimolar amounts of CO, biliverdin and free Fe. The serine/threonine kinase, biliverdin reductase, catalyzes reduction of biliverdin to bilirubin. Bilirubin is a potent antioxidant and CO is a signal molecule. Although both active HO isozymes catalyze the same reaction, HO-1 and HO-2 may function in a rather distinct fashion in protection against tissue injury. HO-1 is the stress responsive cognate that is rapidly induced by free and stable radicals as well as by hypoxia. Supra induction of HO-1 completely protects ischemic kidney against tissue pathology. This involves rapid inactivation of the pro-oxidant heme of denatured hemoproteins and converting it to bilirubin and CO. In the case of severe tissue injury, such as compression injury, HO-1 is induced and colocalizes with cGMP and pro-apoptotic oncogenes. HO-2, which is the constitutive form, in addition to maintaining cell heme homeostasis, inactivates NO derived radicals. The isozyme binds the free radical at its “heme regulatory motifs” and is “suicide” inactivated at the protein and transcript levels. Data are shown that provide evidence for role of the HO system in the cellular defense mechanism against free radical-mediated tissue damage, and are consistent with the forwarded concept that HO isozymes have common, as well as distinct, roles in cellular defense mechanisms.

Key words

bile pigments carbon monoxide formation heme oxygenase kidney ischemia/reperfusion oxidative stress spinal cord injury 

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References

  1. 1.
    Amersi F, Buelow R, Kato H, Ke B., Coito AJ, Shen XD, Zhao D, Zaky J, Melinek J, Lassman CR, Kolls JK, Alam J, Ritter T, Volk HD, Farmer DG, Ghobrial RM, Busuttil RW, and Kupiec WJ. Upregulation of heme oxygenase-1 protects genetically fat Zucker rat livers from ischemia/reperfusion injury. J Clin Invest 104:1631–9, 1999.PubMedCrossRefGoogle Scholar
  2. 2.
    Aust SD, and Svingen BA. Role of Fe in enzymatic lipid peroxidation. NY: Acad Press, 1982.Google Scholar
  3. 3.
    Beckman JS, and Koppenol WH. Nitric oxide, superoxide and peroxynitrite: the good, the bad, and the ugly. Am J Physiol 40:C1424-C1437, 1996.Google Scholar
  4. 4.
    Bergeron M, Ferriero DM, and Vreman HJ, Stevenson DK, Sharp FR. Hypoxia-ischemia, but not hypoxia alone, induces the expression of heme oxygenase-1 (HSP32) in newborn rat brain. J Cereb Blood Flow Metab 17:647–658, 1997.PubMedCrossRefGoogle Scholar
  5. 5.
    Brune B, and Ullrich V. Inhibition of platelet aggregation by carbon monoxide is mediated by activation of guanylate cyclase. Mol Pharmacol 32:497–504, 1987.PubMedGoogle Scholar
  6. 6.
    Chen K, Gunter K, and Maines MD. Nitric oxide induces heme oxygenase-1 via mitogen- activated protein kinases ERK and p38. Cell Mol Biol 46:609–617, 2000.PubMedGoogle Scholar
  7. 7.
    Cruse I, Maines MD. Evidence suggesting that the two forms of heme oxygenase are products of different genes. J Biol Chem 263:3348–3353, 1988.PubMedGoogle Scholar
  8. 8.
    Dennery PA, Spitz, DR, Yang G, Tatarov A, Lee CS, Shegog ML, and Poss KD. Oxygen toxicity and iron accumulation in the lungs of mice lacking heme oxygenase-2. J Clin Invest 101:1001–1011, 1998.PubMedCrossRefGoogle Scholar
  9. 9.
    Ding Y, McCoubrey WJ, and Maines MD. Interaction of heme oxygenase-2 with nitric oxide donors. Is the oxygenase an intracellular ‘sink’ for NO? Eur J Biochem 264:854–861, 1999.PubMedCrossRefGoogle Scholar
  10. 10.
    Dore S, Sampei K, Goto S, Alkayed N J, Guastella D, Blackshaw S, Gallagher M, Traystman RJ, Hum PD, Koehler RC and Snyder SH. Heme oxygenase-2 is neuroprotective in cerebral ischemia. Mol Med 5:656–663, 1999.PubMedGoogle Scholar
  11. 11.
    Durante W, Christodoulides N, Cheng K, Peyton KJ., Sunahara RK, and Schafer AI. cAMP induces heme oxygenase-1 gene expression and carbon monoxide production in vascular smooth muscle. Am J Physiol 273:H317-H323, 1997.PubMedGoogle Scholar
  12. 12.
    Emami A, Schwarty JH, and Borkan. Transient ischemia or heat stress induces a cytoprotectant protein in rat kidney. Am J Physiol 260:F479-F485, 1991.PubMedGoogle Scholar
  13. 13.
    Estevez AG, Spear N, Manuel SM, Barbeito L, Radi R, and Beckman JS. Role of endogenous nitric oxide and peroxynitrite formation in the survival and death of motor neurons in culture. Prog Brain Res 118:269–280, 1998.PubMedCrossRefGoogle Scholar
  14. 14.
    Evans CA. Spintrapping. Aldrichimica Acta 12:23–29, 1979.Google Scholar
  15. 15.
    Ewing J, and Maines MD. Histochemical localization of heme oxygenase-2 protein and mRNA expression in rat brain. Brain Res Prot 1:165–174, 1997.CrossRefGoogle Scholar
  16. 16.
    Ewing JF, and Maines MD. Distribution of constitutive (HO-2) and heat inducible heme oxygenase (HO-1) isozymes in rat testes: HO-2 displays stage-specific expression in germ cells. Endocrinology 136:2294–2302, 1995.PubMedCrossRefGoogle Scholar
  17. 17.
    Ewing JF, and Maines MD. In situ hybridization and immunohistochemical localization of HO-2 mRNA and protein in normal rat brain: Differential distribution of isozyme 1 and 2. Mol Cell Neurosci 3:559–570, 1992.PubMedCrossRefGoogle Scholar
  18. 18.
    Ewing JF, and Maines MD. Rapid induction of heme oxygenase-1 mRNA and protein by hyperthermia in rat brain: heme oxygenase-2 is not a heat shock protein. Proc Natl Acad Sci 88:5364–5348, 1991.PubMedCrossRefGoogle Scholar
  19. 19.
    Ewing JF, Raju VS, and Maines MD. Induction of heart heme oxygenase-1 (HSP32) by hyperthermia: possible role in stress-mediated elevation of cyclic 3′:5′-guanosine monophosphate. J Pharmacol Exp Ther 271:408–14, 1994.PubMedGoogle Scholar
  20. 20.
    Fakhrai H, and Maines MD. Expression and characterization of a cDNA for rat kidney biliverdin reductase. Evidence suggesting the liver and kidney enzymes are the same transcript product. J Biol Chem 267:4023–4029, 1992.PubMedGoogle Scholar
  21. 21.
    Faraci FM, and Sobey CG. Role of soluble guanylate cyclase in dilator responses of the cerebral microcirculation. Brain Res 821:368–373, 1999.PubMedCrossRefGoogle Scholar
  22. 22.
    Foresti R, Clark JE, Green CJ, and Motterlini R. Thiol compounds interact with nitric oxide in regulating heme oxygenase-1 induction in endothelial cells. J Biol Chem 272:18411–18417,1997.PubMedCrossRefGoogle Scholar
  23. 23.
    Hartsfield CL, Alam J, Cook JL, and Choi AM. Regulation of heme oxygenase-1 gene expression in vascular smooth muscle cells by nitric oxide. Am J Physiol 273:L980-L988, 1997.PubMedGoogle Scholar
  24. 24.
    Hopkins PN, Wu LL, Hunt SC, James BC, Vincent GM, and Williams RR. Higher serum bilirubin is associated with decreased risk for early familial coronary artery disease. Arterioscler Thromb Vasc Biol 16:250–255, 1996.PubMedCrossRefGoogle Scholar
  25. 25.
    Ingi T, Chiang G, and Ronnett GV. The regulation of heme turnover and CO biosynthesis in cultured primary rat olfactory receptor neurons. J Neurosci 16:5621–5628, 1996.PubMedGoogle Scholar
  26. 26.
    Kutty RK, and Maines MD. Purification and characterization of biliverdin reductase from the rat liver. J Biol Chem 256:3956–3962,1981.PubMedGoogle Scholar
  27. 27.
    Li X, and Clark JD. Chronic morphine exposure and the expression of heme oxygenase type 2. Mol Brain Res 75:179–184,2000.PubMedCrossRefGoogle Scholar
  28. 28.
    Liu N, Wang X, McCoubrey WK, and Maines MD. Developmentally regulated expression of two transcripts for heme oxygenase-2 with a first exon specific to rat testis; control by corticosterone of the oxygenase protein expression. Gene 241:175–183,2000.PubMedCrossRefGoogle Scholar
  29. 29.
    Liu V, Christou H, Morita T, Laughner E, Semenza GL, and Kourembanas S. Carbon monoxide and nitric oxide suppress the hypoxic induction of vascular endothelial growth factor gene via the 5 ′ enhancer. J Biol Chem 273:15257–15262, 1998.PubMedCrossRefGoogle Scholar
  30. 30.
    Maines MD. Carbon monoxide: An emerging regulator of cGMP in the brain. Mol Cell Neurosci 4:389–397, 1993.PubMedCrossRefGoogle Scholar
  31. 31.
    Maines MD. HEME OXYGENASE: Clinical applications and functions. FL: CRC Press, 1992.Google Scholar
  32. 32.
    Maines MD. The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Tox 37:517–54, 1997.CrossRefGoogle Scholar
  33. 33.
    Maines M.D. New developments in the regulation of heme metabolism and their implications. CRC Critical Rev Toxicol 12:241–314, 1984.CrossRefGoogle Scholar
  34. 34.
    Maines MD, Eke BC, Zhao X. Corticosterone promotes increased heme oxygenase-2 protein and transcript expression in the newborn rat brain. Brain Res 722:83–94, 1996.PubMedCrossRefGoogle Scholar
  35. 35.
    Maines MD, and Kappas A. Cobalt induction of hepatic heme oxygenase; with evidence that cytochrome P-450 is not essential for this enzyme activity. Proc Natl Acad Sci USA 71:4293–4297, 1996.CrossRefGoogle Scholar
  36. 36.
    Maines MD, and Kappas A. Metals as regulators of heme metabolism: physiological and toxicological implications. Science 198:1215–1221, 1977.PubMedCrossRefGoogle Scholar
  37. 37.
    Maines MD, Mark JA, Ewing JF. HO, A likely regulator of cGMP production in the brain: Induction in vivo of HO-1 compensates for depression in NO synthase activity. Mol Cell Neurosci 4:398–405, 1993.Google Scholar
  38. 38.
    Maines MD, Mayer RD, Ewing JF, and McCoubrey WJ. Induction of kidney heme oxygenase-1 (HSP32) mRNA and protein by ischemia/reperfusion: possible role of heme as both promotor of tissue damage and regulator of HSP32. J Pharmacol Exp Ther 264:457–462, 1993.PubMedGoogle Scholar
  39. 39.
    Maines MD, Polevoda BV, Huang TJ, and McCoubrey WJ. Human biliverdin IXalpha reductase is a zinc-metalloprotein. Characterization of purified and Escherichia coli expressed enzymes. Eur J Biochem 235:372–381, 1996.PubMedCrossRefGoogle Scholar
  40. 40.
    Maines MD, Raju VS, and Panahian N. Spin trap (N-t-butyl-alpha-phenylnitrone)- mediated suprainduction of heme oxygenase-1 in kidney ischemia/reperfusion model: role of the oxygenase in protection against oxidative injury. J Pharmacol Exp Ther 291(2):911–919, 1999.PubMedGoogle Scholar
  41. 41.
    Maines MD, Trakshel GM, and Kutty RK. Characterization of two constitutive forms of rat liver microsomal heme oxygenase. Only one molecular species of the enzyme is inducible. J Biol Chem 261:411–941, 1986.PubMedGoogle Scholar
  42. 42.
    Mancuso C, Tringali G, Grossman A, Preziosi P, and Navarra P. The generation of nitric oxide and carbon monoxide produces opposite effects on the release of immunoreactive interleukin-1beta from the rat hypothalamus in vitro: evidence for the involvement of different signaling pathways. Endocrinology 139:1031–1037, 1998.PubMedCrossRefGoogle Scholar
  43. 43.
    Marks GS, Brien JF, Nakakatsa K, and McLaughlin BE. Does carbon monoxide have a physiological function? Trends Pharmacol Sci 12:185–188, 1991.PubMedCrossRefGoogle Scholar
  44. 44.
    McCoubrey WK, Jr, Ewing JF and Maines MD. Human heme oxygenase: characterization and expression of a full length cDNA and evidence suggesting the two HO-2 transcripts differ by choice of polyadenylation signal. Arch Biochem Biophys 295: 13–20, 1992.PubMedCrossRefGoogle Scholar
  45. 45.
    McCoubrey WK, Huang TJ, and Maines MD. Heme oxygenase-2 is a hemoprotein and binds heme through heme regulatory motifs that are not involved in heme catalysis. J Biol Chem 272:12568–12574, 1997.PubMedCrossRefGoogle Scholar
  46. 46.
    McCoubrey WJ, Huang TJ, and Maines MD. Isolation and characterization of a cDNA from the rat brain that encodes hemoprotein heme oxygenase-3. Eur J Biochem 247:725–732, 1997.PubMedCrossRefGoogle Scholar
  47. 47.
    McCoubrey WJ, and Maines MD. The structure, organization and differential expression of the gene encoding rat heme oxygenase-2. Gene 139:155–161, 1994.PubMedCrossRefGoogle Scholar
  48. 48.
    Motterlini R, Gonzales A, Foresti, R, Clark JE, Freen CJ, and Winslow RM. Heme oxygenase-1 derived carbon monoxide contributes to the suppression of acute hypertensive responses in vivo. Cire Res 83:568–577,1998.CrossRefGoogle Scholar
  49. 49.
    Morita T, Perrella MA, Lee M-E, and Kourembanas S. Smooth muscle cell-derived carbon monoxide is a regulator of vascular cGMP. Proc Natl Acad Sci USA 92:1475–1479, 1995.PubMedCrossRefGoogle Scholar
  50. 50.
    Müller RM, Taguchi H, and Shibahara S. Nucleotide sequence and organization of the rat HO gene. J Biol Chem 262:6795–6802, 1987.PubMedGoogle Scholar
  51. 51.
    Nakagami T, Toyomura K, Kinoshita T, and Morisawa S. A beneficial role of bile pigments as an endogenous tissue protector: anti-complement effects of biliverdin and conjugated bilirubin. Biochim Biophys Acta 1158:189–193, 1993.PubMedCrossRefGoogle Scholar
  52. 52.
    Neuzil J, and Stocker R Free and albumin-bound bilirubin are efficient co-antioxidants for alpha-tocopherol, inhibiting plasma and low density lipoprotein lipid peroxidation. J Biol Chem 269:16712–16719, 1994.PubMedGoogle Scholar
  53. 53.
    Nimura T, Weinstein PR, Massa SM, Panter S, and Sharp FR. Heme oxygenase-1 (HO-1) protein induction in rat brain following focal ischemia. Brain Res Mol Brain Res 37:201–208, 1996.PubMedCrossRefGoogle Scholar
  54. 54.
    Panahian N, and Maines MD. Site of injury-directed induction of heme oxygenase-1 and- 2 in experimental spinal cord injury: differential functions in neuronal defense mechanisms? J Neurochem 76:539–554, 2001.PubMedCrossRefGoogle Scholar
  55. 55.
    Panahian N, Yoshiura M, and Maines MD. Overexpression of heme oxygenase-1 is neuroprotective in a model of permanent middle cerebral artery occlusion in transgenic mice. J Neurochem 72: 1187–203, 1999.PubMedCrossRefGoogle Scholar
  56. 56.
    Parry N, Buelow R, Jiang J, Garcia B, and Zhong R A rationally designed immunomodulatory peptide upregulates expression of heme oxygenase 1 and attenuates chronic rejection in a rat renal allograft model. Transplantation 67:5252–5258, 1999.CrossRefGoogle Scholar
  57. 57.
    Phillis JW. Free radical scavengers and spin trips. In Primer on Cerebrovascular Diseases. 75:261–265, 1997.CrossRefGoogle Scholar
  58. 58.
    Polte T, Abate A, Dennery PA, Schroder H. Heme oxygenase-1 is a cGMP-inducible endothelial protein and mediates the cytoprotective action of nitric oxide. Arterioscler Thromb Vasc Biol 20:1209–1215,2000.PubMedCrossRefGoogle Scholar
  59. 59.
    Pompella A, Maellaro E, Casini AF, and Comporti M. Histochemical detection of lipid peroxidation in the liver of bromobenzene-poisoned mice. Am J Path 129:295–301, 1987.PubMedGoogle Scholar
  60. 60.
    Ponka P, Beaumont C, and Richardson DR. Function and regulation of transferrin and ferritin. Hematology 35:35–54, 1998.Google Scholar
  61. 61.
    Possoli G, Mancuso C, Mirtelia A, Preziosi P, Grossman A B, and Navara P. Carbon monoxide as a novel neuroendocrine modulator: Inhibition of stimulated corticotrophin-releasing hormone release from acute rat hypothalamic expiants. Endocrinology 135:2314–2317, 1994.CrossRefGoogle Scholar
  62. 62.
    Prabhakar R, Dinerman JL, Agani FH, and Snyder SH. CO: a role in carotid body chemoreception. Proc Natl Acad Sci USA 92:1994–1997, 1995.PubMedCrossRefGoogle Scholar
  63. 63.
    Raju VS, and Maines MD. Renal ischemia/reperfusion up-regulates heme oxygenase-1 (HSP32) expression and increases cGMP in rat heart. J Pharmacol Exp Ther 277:1814–22, 1996.PubMedGoogle Scholar
  64. 64.
    Raju VS, McCoubrey WK, and Maines MD. Regulation of HO-2 mRNA and protein by glucocorticoids: characterization of a functional GRE. Biochim Biophys Acta 351:89–104, 1997.Google Scholar
  65. 65.
    Rattan S, and Chakder S. Inhibitory effect of CO on internal sphincter: HO inhibitor inhibits NANC relaxation. Am J Physiol 265:G799-G804, 1993.PubMedGoogle Scholar
  66. 66.
    Rotenberg MO, and Maines MD. Isolation, characterization, and expression in Escherichia coli of a cDNA encoding rat heme oxygenase-2. J Biol Chem 265:7501–7506, 1990.PubMedGoogle Scholar
  67. 67.
    Salim M, Brown BA, and Maines MD. Human biliverdin reductase is autophosphorylated and phosphorylation is required for bilirubin formation. J Biol Chem in press, 2001.Google Scholar
  68. 68.
    Shibahara S, Muller R, Taguchi H, and Yoshida T. Cloning and expression of a cDNA for rat heme oxygenase. Proc Natl Acad Sci USA 82:7865–7878, 1985.PubMedCrossRefGoogle Scholar
  69. 69.
    Smith MA, Richey PL, Kutty RK, Wiggert B, and Perry G. Ultrastructural localization of heme oxygenase-1 to the neurofibrillary pathology of Alzheimer’s disease. Mol Chem Neuropath 24:227–230, 1995.CrossRefGoogle Scholar
  70. 70.
    Snyder SH, Jaffrey SR, and Zakhary R. Nitric oxide and carbon monoxide: parallel roles as neural messengers. Brain Res Brain Res Rev 26:167–175, 1998.PubMedCrossRefGoogle Scholar
  71. 71.
    Soares MP, Lin Y, Anrather J, Csizmadia E, Takigami K, Sato K, Grey ST, Colvin RB, Choi AM, Poss KD, and Bach FH. Expression of heme oxygenase-1 can determine cardiac xenograft survival. Nat Med 4:1073–1077, 1998.PubMedCrossRefGoogle Scholar
  72. 72.
    Stocker R. Induction of haem oxygenase as a defense against oxidative stress. Free Rad Res Commun 9:101–112,1990.CrossRefGoogle Scholar
  73. 73.
    Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, and Ames BN. Bilirubin is an antioxidant of possible physiological importance. Science 235:1043–1047, 1987.PubMedCrossRefGoogle Scholar
  74. 74.
    Suematsu M, Kashiwagi S, Sano T, Goda N, Shinoda Y, and Ishimura Y. Carbon monoxide as an endogenous modulator of hepatic vascular perfusion. Biochem Biophys Res Commun 205:1332–1337, 1994.CrossRefGoogle Scholar
  75. 75.
    Sun Y, Rotenberg MO, and Maines MD. Developmental expression of heme oxygenase isozymes in rat brain. Two HO-2 mRNAs are detected. J Biol Chem 265:8212–8217, 1990.PubMedGoogle Scholar
  76. 76.
    Takeda A, Parry G, Abraham NG, Dwyer BE, Kutty RK, Laitinen JT, Petersen RB and Smith MA. Overexpression of heme oxygenase in neuronal cells, the possible interaction with Tau. J Biol Chem 275:5395–5399, 2000.PubMedCrossRefGoogle Scholar
  77. 77.
    Tamaka J, Markerink-van Ittersum M, Steinbusch HWM, and de Vente J. Nitric oxide-mediated cyclic GMP synthesis in oligodendrocytes in the developing rat brain. Glia 19:286–297, 1997.CrossRefGoogle Scholar
  78. 78.
    Thorn SR, Fisher D, Xu YA, Notarfrancesco K, and Ischiropoulos IH. Adaptive responses and apoptosis in endothelial cells exposed to carbon monoxide. Proc Natl Acad Sci USA 97:1305–1320, 2000.CrossRefGoogle Scholar
  79. 79.
    Trakshel GM, Kutty RK, and Maines MD. Purification and characterization of the major constitutive form of testicular heme oxygenase. The noninducible isoform. J Biol Chem 261:11131–11137, 1986.PubMedGoogle Scholar
  80. 80.
    Verma A, Hirsh D, Glatt CE, Ronnett G. V., and Snyder S. H. CO: A putative neural messenger. Science 259:381–383, 1993.PubMedCrossRefGoogle Scholar
  81. 81.
    Vile GF, Basu-Modak S, Waltner C, and Tyrrell RM. Heme oxygenase-1 mediates an adaptive response to oxidative stress in human skin fibroblasts. Proc Natl Acad Sci USA 91:2607–2610, 1994.PubMedCrossRefGoogle Scholar
  82. 82.
    Vincent SR, Das S, and Maines MD. Brain heme oxygenase isoenzymes and nitric oxide synthase are co-localized in select neurons. Neuroscience 63: 223–231, 1994.PubMedCrossRefGoogle Scholar
  83. 83.
    von Euler M, Seiger A, and Sundstrom E. Clip compression injury in the spinal cord: a correlative study of neurological and morphological alterations. Exp Neurol 145:502–510, 1997.CrossRefGoogle Scholar
  84. 84.
    Weber CM, Eke BC, and Maines MD. Corticosterone regulates heme oxygenase-2 and NO synthase transcription and protein expression in rat brain. J Neurochem 63:953–962, 1994.PubMedCrossRefGoogle Scholar
  85. 85.
    Weiner CP, Knowles RG, Nelson SE, and Stegink LD. Pregnancy increases guanosine 3′-5′ monophosphate in myometrium independent of NOS. Endocrinology 135:2473–2478, 1994.PubMedCrossRefGoogle Scholar
  86. 86.
    Weiss G, Werner-Felmayer G, Werner ER, Grünewald K, Wachter H, and Hentze MW. Iron regulates NO synthase activity by controlling nuclear transcription. J Expt Med 1994; 180:969–976.CrossRefGoogle Scholar
  87. 87.
    Willis D, Moore AR, and Willoughby DA. Heme oxygenase isoform expression in cellular and antibody-mediated models of acute inflammation in the rat. J Pathol 190:627–634, 2000.PubMedCrossRefGoogle Scholar
  88. 88.
    Wink DA, Nims RW, Darbyshire JF, Christodoulou D, Hanbauer I, Cox GW, Laval F, Laval J, Cook JA, and Krishna MC, et al. Reaction kinetics for nitrosation of cysteine and glutathione in aerobic nitric oxide solutions at neutral pH. Insights into the fate and physiological effects of intermediates generated in the NO/O2 reaction. Chem Res Toxicol 7:519–525, 1994.PubMedCrossRefGoogle Scholar
  89. 89.
    Woo J, Iyer S. Cornejo M-C, Mori N, Gao L, Maines MD, and Buelow R. Stress protein induced immunosuppression: inhibition of cellular immune effector functions following overexpression of heme oxygenase-1 (hsp 32). Transplant Immunol 6:85–93, 1998.CrossRefGoogle Scholar
  90. 90.
    Zhou M, Small SA, Kandel ER, and Hawkins RD. Nitric oxide and carbon monoxide produce activity-dependent long term synaptic enhancement in hippocampus. Science 260:1946–1950, 1993.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Mahin D. Maines
    • 1
  • Nariman Panahian
    • 1
  1. 1.Department of Biochemistry/BiophysicsUniversity of Rochester Medical CenterRochesterUSA

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