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Introduction

  • Adi Haber
Chapter
Part of the Springer Theses book series (Springer Theses)

Abstract

“Free radicals” is the term commonly used for molecules or ions that contain an odd number of electrons. The unavoidable presence of (at least) one unpaired electron has an enormous impact on the chemical reactivity of free radicals. They react very fast with non-radical species by either abstraction of an electron (acting as an oxidizing agent), donation of an electron (acting as a reducing agent), or by attachment to the non-radical (Slater, Biochem J 222:1–5, 1984). The product formed in the latter case (commonly termed secondary radical) also contains an unpaired electron, and hence may react with another non-radical and propagate a chain reaction.

Keywords

High Density Lipoprotein Reactive Nitrogen Species Reverse Cholesterol Transport Cholesterol Ester Transfer Protein Peroxynitrous Acid 
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.

References

  1. 1.
    Slater, T.F.: Free-radical mechanisms in tissue injury. Biochem. J. 222, 1–15 (1984)Google Scholar
  2. 2.
    Cadenas, E.: Basic mechanisms of antioxidant activity. BioFactors 6, 391–397 (1997)CrossRefGoogle Scholar
  3. 3.
    Finkel, T., Holbrook, N.J.: Oxidants, oxidative stress and the biology of ageing. Nature 408, 239–247 (2000)CrossRefGoogle Scholar
  4. 4.
    Fridovich, I.: Superoxide radical: an endogenous toxicant. Annu. Rev. Pharmacol. Toxicol. 23, 239–257 (1983)CrossRefGoogle Scholar
  5. 5.
    Griendling, K.K., Sorescu, D., Ushio-Fukai, M.: NAD(P)H oxidase : role in cardiovascular biology and disease. Circul. Res. 86, 494–501 (2000)CrossRefGoogle Scholar
  6. 6.
    Pagano, P.J., et al.: An NADPH oxidase superoxide-generating system in the rabbit aorta. Am. J. Physiol. 268, H2274–H2280 (1995)Google Scholar
  7. 7.
    Fridovich, I.: Superoxide dismutases. Annu. Rev. Biochem. 44, 147–159 (1975)CrossRefGoogle Scholar
  8. 8.
    Chance, B., Sies, H., Boveris, A.: Hydroperoxide metabolism in mammalian organs. Physiol. Rev. 59, 527–605 (1979)Google Scholar
  9. 9.
    Fleming, I., Busse, R.: Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase. Am. J. Physiol. 284, R1–R12 (2003)Google Scholar
  10. 10.
    Vásquez-Vivar, J., et al.: Superoxide generation by endothelial nitric oxide synthase: the influence of cofactors. Proc. Natl. Acad. Sci. USA 95, 9220–9225 (1998)CrossRefGoogle Scholar
  11. 11.
    Kelm, M., Dahmann, R., Wink, D., Feelisch, M.: The nitric oxide/superoxide assay. J. Biol. Chem. 272, 9922–9932 (1997)CrossRefGoogle Scholar
  12. 12.
    Pacher, P., Beckman, J.S., Liaudet, L.: Nitric oxide and peroxynitrite in health and disease. Physiol. Rev. 87, 315–424 (2007)CrossRefGoogle Scholar
  13. 13.
    Ducrocq, C., Blanchard, B.: Peroxynitrite: an endogenous oxidizing and nitrating agent. Cell. Mol. Life Sci. 55, 1068–1077 (1999)CrossRefGoogle Scholar
  14. 14.
    Ross, R.: The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362, 801–809 (1993)CrossRefGoogle Scholar
  15. 15.
    Glass, C.K., Witztum, J.L.: Atherosclerosis: the road ahead. Cell 104, 503–516 (2001)CrossRefGoogle Scholar
  16. 16.
    Brown, M.S., Goldstein, J.L.: The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 89, 331–340 (1997)CrossRefGoogle Scholar
  17. 17.
    Stocker, R., Keaney, J.F.: New insights on oxidative stress in the artery wall. J. Thromb. Haemost. 3, 1825–1834 (2005)CrossRefGoogle Scholar
  18. 18.
    Palinski, W., et al.: Low density lipoprotein undergoes oxidative modification in vivo. Proc. Natl. Acad. Sci. USA 86, 1372–1376 (1989)CrossRefGoogle Scholar
  19. 19.
    Nishi, K., et al.: Oxidized LDL in carotid plaques and plasma associates with plaque instability. Atert. Thromb. Vasc. Biol. 22, 1649–1654 (2002)CrossRefGoogle Scholar
  20. 20.
    Ehara, S., et al.: Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes. Circulation 103, 1955–1960 (2001)CrossRefGoogle Scholar
  21. 21.
    Aviram, M., Fuhrman, B.: LDL oxidation by arterial wall macrophages depends on the oxidative status in the lipoprotein and in the cells: role of prooxidants vs. antioxidants. Mol. Cell. Biochem. 188, 149–159 (1998)CrossRefGoogle Scholar
  22. 22.
    Leeuwenburgh, C., et al.: Reactive nitrogen intermediates promote low density lipoprotein oxidation in human atherosclerotic intima. J. Biol. Chem. 272, 1433–1436 (1997)CrossRefGoogle Scholar
  23. 23.
    Kontush, A., Chapman, M.J.: Functionally defective high-density lipoprotein: a new therapeutic target at the crossroads of dyslipidemia, inflammation, and atherosclerosis. Pharmacol. Rev. 58, 342–374 (2006)CrossRefGoogle Scholar
  24. 24.
    Kontush, A., Chapman, M.J.: Antiatherogenic small, dense HDL—guardian angel of the arterial wall? Nat. Clin. Pract. Cardiovasc. Med. 3, 144–153 (2006)CrossRefGoogle Scholar
  25. 25.
    Aviram, M., Rosenblat, M.: Paraoxonases 1, 2, and 3, oxidative stress, and macrophage foam cell formation during atherosclerosis development. Free Radic. Biol. Med. 37, 1304–1316 (2004)CrossRefGoogle Scholar
  26. 26.
    Nakajima, T., et al.: Characterization of the epitopes specific for the monoclonal antibody 9F5-3a and quantification of oxidized HDL in human plasma. Ann. Clin. Biochem. 41, 309–315 (2004)CrossRefGoogle Scholar
  27. 27.
    Zheng, L., et al.: Apolipoprotein A-I is a selective target for myeloperoxidase-catalyzed oxidation and functional impairment in subjects with cardiovascular disease. J. Clin. Invest. 114, 529–541 (2004)Google Scholar
  28. 28.
    Francis, G.A.: High density lipoprotein oxidation: in vitro susceptibility and potential in vivo consequences. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1483, 217–235 (2000)CrossRefGoogle Scholar
  29. 29.
    Grundy, S.M., et al.: Implications of recent clinical trials for the national cholesterol education program adult treatment panel III guidelines. Circulation 110, 227–239 (2004)CrossRefGoogle Scholar
  30. 30.
    Lenfant, C.: Clinical research to clinical practice—lost in translation? N. Engl. J. Med. 349, 868–874 (2003)CrossRefGoogle Scholar
  31. 31.
    Steinberg, D., Glass, C.K., Witztum, J.L.: Evidence mandating earlier and more aggressive treatment of hypercholesterolemia. Circulation 118, 672–677 (2008)CrossRefGoogle Scholar
  32. 32.
    Waters, D.D., et al.: Predictors of new-onset diabetes in patients treated with atorvastatin: results from 3 large randomized clinical trials. J. Am. Coll. Cardiol. 57, 1535–1545 (2011)CrossRefGoogle Scholar
  33. 33.
    Preiss, D., et al.: Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy. JAMA J. Am. Med. Assoc. 305, 2556–2564 (2011)CrossRefGoogle Scholar
  34. 34.
    Rietjens, I.M.C.M., et al.: The pro-oxidant chemistry of the natural antioxidants vitamin C, vitamin E, carotenoids and flavonoids. Environ. Toxicol. Pharmacol. 11, 321–333 (2002)CrossRefGoogle Scholar
  35. 35.
    Fuhrman, B., Aviram, M.: Anti-atherogenicity of nutritional antioxidants. IDrugs 4, 82–92 (2001)Google Scholar
  36. 36.
    Steinhubl, S.R.: Why have antioxidants failed in clinical trials? Am. J. Cardiol. 101, 14D–19D (2008)CrossRefGoogle Scholar
  37. 37.
    Bjelakovic, G., Nikolova, D., Gluud, L.L., Simonetti, R.G., Gluud, C.: Mortality in randomized trials of antioxidant supplements for primary and secondary prevention—Systematic review and meta-analysis. JAMA, J. Am. Med. Assoc. 297, 842–857 (2007)Google Scholar
  38. 38.
    Gross, Z., Galili, N., Saltsman, I.: The first direct synthesis of corroles from pyrrole. Angew. Chem., Int. Ed. 38, 1427–1429 (1999)Google Scholar
  39. 39.
    Mahammed, A., Goldberg, I., Gross, Z.: Highly selective chlorosulfonation of tris(pentafluorophenyl)corrole as a synthetic tool for the preparation of amphiphilic corroles and metal complexes of planar chirality. Org. Lett. 3, 3443–3446 (2001)CrossRefGoogle Scholar
  40. 40.
    Saltsman, I., et al.: Selective substitution of corroles: nitration, hydroformylation, and chlorosulfonation. J. Am. Chem. Soc. 124, 7411–7420 (2002)CrossRefGoogle Scholar
  41. 41.
    Haber, A., Aviram, M., Gross, Z.: Protecting the beneficial functionality of lipoproteins by 1-Fe, a corrole-based catalytic antioxidant. Chem. Sci. 2, 295–302 (2011)CrossRefGoogle Scholar
  42. 42.
    Kanamori, A., Catrinescu, M.M., Mahammed, A., Gross, Z., Levin, L.A.: Neuroprotection against superoxide anion radical by metallocorroles in cellular and murine models of optic neuropathy. J. Neurochem. 114, 488–498 (2010)CrossRefGoogle Scholar
  43. 43.
    Kupershmidt, L., et al.: Metallocorroles as cytoprotective agents against oxidative and nitrative stress in cellular models of neurodegeneration. J. Neurochem. 113, 363–373 (2010)CrossRefGoogle Scholar
  44. 44.
    Okun, Z., et al.: Manganese corroles prevent intracellular nitration and subsequent death of insulin-producing cells. ACS Chem. Biol. 4, 910–914 (2009)CrossRefGoogle Scholar
  45. 45.
    Haber, A., et al.: Amphiphilic/bipolar metallocorroles that catalyze the decomposition of reactive oxygen and nitrogen species, rescue lipoproteins from oxidative damage, and attenuate atherosclerosis in mice. Angew. Chem. Int. Ed. 47, 7896–7900 (2008)Google Scholar
  46. 46.
    Agadjanian, H., et al.: Tumor detection and elimination by a targeted gallium corrole. Proc. Natl. Acad. Sci. USA 106, 6105–6110 (2009)CrossRefGoogle Scholar
  47. 47.
    Agadjanian, H., et al.: Specific delivery of corroles to cells via noncovalent conjugates with viral proteins. Pharm. Res. 23, 367–377 (2006)CrossRefGoogle Scholar
  48. 48.
    Aviv, I., Gross, Z.: Corrole-based applications. Chem. commun. (20), 1987–1999 (2007)Google Scholar
  49. 49.
    Gross, Z., Gray, H.B.: How do corroles stabilize high valent metals? Comments Inorg. Chem. 27, 61–72 (2006)CrossRefGoogle Scholar
  50. 50.
    Simonson, S.G., et al.: Aerosolized manganese SOD decreases hyperoxic pulmonary injury in primates. I. Physiology and biochemistry. J. Appl. Physiol. 83, 550–558 (1997)Google Scholar
  51. 51.
    Salvemini, D., Wang, Z.-Q., Stern, M.K., Currie, M.G., Misko, T.P.: Peroxynitrite decomposition catalysts: therapeutics for peroxynitrite-mediated pathology. Proc. Natl. Acad. Sci. USA 95, 2659–2663 (1998)CrossRefGoogle Scholar
  52. 52.
    Batinić-Haberle, I., Rebouças, J.S., Spasojević, I.: Superoxide dismutase mimics: chemistry, pharmacology, and therapeutic potential. Antioxid. Redox Signal. 13, 877–918 (2010)CrossRefGoogle Scholar
  53. 53.
    Eckshtain, M., et al.: Superoxide dismutase activity of corrole metal complexes. Dalton Trans. (38), 7879–7882 (2009)Google Scholar
  54. 54.
    Mahammed, A., Gross, Z.: Highly efficient catalase activity of metallocorroles. Chem. Comm. 46, 7040–7042 (2010)CrossRefGoogle Scholar
  55. 55.
    Mahammed, A., Gross, Z.: Iron and manganese corroles are potent catalysts for the decomposition of peroxynitrite. Angew. Chem. Int. Ed. 45, 6544–6547 (2006)CrossRefGoogle Scholar
  56. 56.
    Lee, J., Hunt, J.A., Groves, J.T.: Manganese porphyrins as redox-coupled peroxynitrite reductases. J. Am. Chem. Soc. 120, 6053–6061 (1998)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Technion—Israel Institute of TechnologyHaifaIsrael

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