Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지

Oxidative Modification of Cytochrome c by Hydrogen Peroxide

  • Kim, Nam Hoon (Department of Genetic Engineering, Cheongju University) ;
  • Jeong, Moon Sik (Department of Genetic Engineering, Cheongju University) ;
  • Choi, Soo Young (Department of Biomedical Science, Division of Life Sciences, Hallym University) ;
  • Kang, Jung Hoon (Department of Genetic Engineering, Cheongju University)
  • Received : 2006.07.27
  • Accepted : 2006.08.24
  • Published : 2006.10.31
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Abstract

Oxidative alteration of mitochondrial cytochrome c has been linked to disease and is one of the causes of proapoptotic events. We have investigated the modification of cytochrome c by $H_2O_2$. When cytochrome c was incubated with $H_2O_2$, oligomerization of the protein increased and the formation of carbonyl derivatives and dityrosine was stimulated. Radical scavengers prevented these effects suggesting that free radicals are implicated in the $H_2O_2$-mediated oligomerization. Oligomerization was significantly inhibited by the iron chelator, deferoxamine. During incubation of deoxyribose with cytochrome c and $H_2O_2$, damage to the deoxyribose occurred in parallel with the release of iron from cytochrome c. When cytochrome c that had been exposed to $H_2O_2$ was analyzed by amino acid analysis, the tyrosine, histidine and methionine residues proved to be particularly sensitive. These results suggest that $H_2O_2$-mediated cytochrome c oligomerization is due to oxidative damage resulting from free radicals generated by a combination of the peroxidase activity of cytochrome c and the Fenton reaction of free iron released from the oxidatively-damaged protein.

Keywords

Acknowledgement

Supported by : Korea Research Foundation

References

  1. Atwood, C. S., Perry, G., Zeng, H., Kato, Y., Jones, W. D., et al. (2004) Copper mediates dityrosine cross-linking of Alzheimer's amyloid-beta. Biochemistry 43, 560−568 https://doi.org/10.1021/bi0358824
  2. Banci, L., Bertini, I., Cavallaro, G., and Luchinat, C. (2002) Chemical shift-based constraints for solution structure determination of paramagnetic low-spin heme proteins with bis-His and His-CN axial ligands: the cases of oxidized cytochrome b(5) and Met80Ala cyano- cytochrome c. J. Biol. Inorg. Chem. 7, 416−426 https://doi.org/10.1007/s00775-001-0313-3
  3. Barr, D. P., Gunther, M. R., Deterding, L. J., Tomer, K. B., and Mason, R. P. (1996) ESR spin-trapping of a protein-derived tyrosyl radical from the reaction of cytochrome c with hydrogen peroxide. J. Biol. Chem. 271, 15498−15503 https://doi.org/10.1074/jbc.271.26.15498
  4. Berlett, B. S. and Stadtman, E. R. (1997) Protein oxidation in aging, disease, and oxidative stress. J. Biol. Chem. 272, 20313− 20316
  5. Cadenas, E., Boveris, A., and Chance, B. (1980) Low-level chemiluminescence of hydroperoxide - supplemented cytochrome c. Biochem. J. 187, 131−140
  6. Chen, Y. R., Deterding, L. J., Sturgeon, B. E., Tomer, K. B., and Mason, R. P. (2002) Protein oxidation of cytochrome c by reactive halogen species enhances its peroxidase activity. J. Biol. Chem. 277, 29781−29791
  7. Davies, K. J. (1986) Intracellular proteolytic systems may function as secondary antioxidant defenses: a hypothesis. J. Free Radic. Biol. Med. 2, 155−173 https://doi.org/10.1016/S0748-5514(86)80066-6
  8. Deshmukh, M. and Johnson, E. M., Jr. (1998) Evidence of a novel event during neuronal death: development of competence- to-die in response to cytoplasmic cytochrome c. Neuron 21, 695−705 https://doi.org/10.1016/S0896-6273(00)80587-5
  9. Dumont, M. E., Cardillo, T. S., Hayes, M. K., and Sherman, F. (1991) Role of cytochrome c heme lyase in mitochondrial import and accumulation of cytochrome c in Saccharomyces cerevisiae. Mol. Cell. Biol. 11, 5487−5496
  10. Dumont, M. E., Corin, A. F., and Campbell, G. A. (1994) Noncovalent binding of heme induces a compact apocytochrome c structure. Biochemistry 33, 7368−7378
  11. Flaherty, J. T. and Weisfeldt, M. L. (1988) Reperfusion injury. Free Radic. Biol. Med. 5, 409−419
  12. Friedlander, R. M. (2003) Apoptosis and caspases in neurodegenerative diseases. N. Engl. J. Med. 348, 1365−1375 https://doi.org/10.1056/NEJMra022366
  13. Giulivi, C. and Davies, K. J. (1993) Dityrosine and tyrosine oxidation products are endogenous markers for the selective proteolysis of oxidatively modified red blood cell hemoglobin by (the 19 S) proteasome. J. Biol. Chem. 268, 8752−8759
  14. Green, D. R. and Evan, G. I. (2002) A matter of life and death. Cancer Cell 1, 19−30
  15. Halliwell, B. and Gutteridge, J. M. (1981) Formation of thiobarbituric- acid-reactive substance from deoxyribose in the presence of iron salts: the role of superoxide and hydroxyl radicals. FEBS Lett. 128, 347−352 https://doi.org/10.1016/0014-5793(81)80114-7
  16. Halliwell, B. and Gutteridge, J. M. C. (1999) Free Radicals in Biology and Medicine, Oxford Press, New York
  17. Hashimoto, M., Takeda, A., Hsu, L. J., Takenouchi, T., and Masliah, E. (1999) Role of cytochrome c as a stimulator of alpha-synuclein aggregation in Lewy body disease. J. Biol. Chem. 274, 28849−28852 https://doi.org/10.1074/jbc.274.41.28849
  18. Heinecke, J. W., Li, W., Daehnke, H. L. 3rd, and Goldstein, J. A. (1993) Dityrosine, a specific marker of oxidation, is synthesized by the myeloperoxidase-hydrogen peroxide system of human neutrophils and macrophages. J. Biol. Chem. 268, 4069−4077
  19. Huggins, T. G., Wells-Knecht, M. C., Detorie, N. A., Baynes, J. W., and Thorpe, S. R. (1993) Formation of o-tyrosine and dityrosine in proteins during radiolytic and metal-catalyzed oxidation. J. Biol. Chem. 268, 12341−12347
  20. Hugli, T. E. and Moore, S. (1972) Determination of the tryptophan content of proteins by ion exchange chromatography of alkaline hydrolysates. J. Biol. Chem. 247, 2828−2834
  21. Imlay, J. A., Chin, S. M., and Linn, S. (1988) Toxic DNA damage by hydrogen peroxide through the Fenton reaction in vivo and in vitro. Science 240, 640−642
  22. Kato, Y., Kitamoto, N., Kawai, Y., and Osawa, T. (2001) The hydrogen peroxide/copper ion system, but not other metalcatalyzed oxidation systems, produces protein-bound dityrosine. Free Radic. Biol. Med. 31, 624−632 https://doi.org/10.1016/S0891-5849(01)00623-2
  23. Kim, C. S., Lee, C.-H., Lee, P. H., and Han, S. (2004) Inactivation of mitochondrial electron transport by photosensitization of a pheophorbide a derivative. Mol. Cells 17, 347−352
  24. Laemmli, U. K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680−685
  25. Lawrence, A., Jones, C. M., Wardman, P., and Burkitt, M. J. (2003) Evidence for the role of a peroxidase compound Itype intermediate in the oxidation of glutathione, NADH, ascorbate, and dichlorofluorescin by cytochrome c/$H_2O_2$. Implications for oxidative stress during apoptosis. J. Biol. Chem. 278, 29410−29419 https://doi.org/10.1074/jbc.M300054200
  26. Levine, R. L., Williams, J. A., Stadtman, E. R., and Shacter, E. (1994) Carbonyl assays for determination of oxidatively modified proteins. Methods Enzymol. 233, 346−357
  27. Li, P., Nijhawan, D., Budihardjo, I., Srinivasula, S. M., Ahmad, M., et al. (1997) cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91, 479−489 https://doi.org/10.1016/S0092-8674(00)80434-1
  28. Liu, X., Kim, C. N., Yang, J., Jemmerson, R., and Wang, X. (1996) Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86, 147−157 https://doi.org/10.1016/S0092-8674(00)80085-9
  29. Millett, F. and Scott, R. (1996) In cytochrome c, A Multidisciplinary Approach, Mauk, A. G. and Scott, R. A. (eds.), pp. 475−487, University Science Books, Sausalito, CA
  30. Moore, G. R. and Pettigrew, G. W. (1990) cytochrome c: Evolutionary, Structure, and Physicochemical Aspects, Springer- Verlag, Berlin
  31. O'Connell, M. J. and Peters, T. J. (1987) Ferritin and haemosiderin in free radical generation, lipid peroxidation and protein damage. Chem. Phys. Lipids 45, 241−249
  32. Oliver, C. N., Levine, R. L., and Stadtman, E. R. (1987) A role of mixed-function oxidation reactions in the accumulation of altered enzyme forms during aging. J. Am. Geriatr. Soc. 35, 947−956
  33. Pelletier, H. and Kraut, J. (1992) Crystal structure of a complex between electron transfer partners, cytochrome c peroxidase and cytochrome c. Science 258, 1748−1755
  34. Pennathur, S., Jackson-Lewis, V., Przedborski, S., and Heinecke, J. W. (1999) Mass spectrometric quantification of 3-nitrotyrosine, ortho-tyrosine, and o,o′-dityrosine in brain tissue of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice, a model of oxidative stress in Parkinson's disease. J. Biol. Chem. 274, 34621−34628 https://doi.org/10.1074/jbc.274.49.34621
  35. Petrosillo, G., Ruggiero, F. M., Pistolese, M., and Paradies, G. (2001) Reactive oxygen species generated from the mitochondrial electron transport chain induce cytochrome c dissociation from beef-heart submitochondrial particles via cardiolipin peroxidation. Possible role in the apoptosis. FEBS Lett. 509, 435−438 https://doi.org/10.1016/S0014-5793(01)03206-9
  36. Pieroni, L., Khalil, L., Charlotte, F., Poynard, T., Piton, A., et al. (2001) Comparison of bathophenanthroline sulfonate and ferene as chromogens in colorimetric measurement of low hepatic iron concentration. Clin. Chem. 47, 2059−2061
  37. Radi, R., Thomson, L., Rubbo, H., and Prodanov, E. (1991) cytochrome c-catalyzed oxidation of organic molecules by hydrogen peroxide. Arch. Biochem. Biophys. 288, 112−117 https://doi.org/10.1016/0003-9861(91)90171-E
  38. Radi, R., Sims, S., Cassina, A., and Turrens, J. F. (1993) Roles of catalase and cytochrome c in hydroperoxide-dependent lipid peroxidation and chemiluminescence in rat heart and kidney mitochondria. Free Radic. Biol. Med. 15, 653−659 https://doi.org/10.1016/0891-5849(93)90169-U
  39. Sagripanti, J. L. and Kraemer, K. H. (1989) Site-specific oxidative DNA damage at polyguanosines produced by copper plus hydrogen peroxide. J. Biol. Chem. 264, 1729−1734
  40. Sagripanti, J. L., Swicord, M. L., and Davis, C. C. (1987) Microwave effects on plasmid DNA. Radiat. Res. 110, 219−231
  41. Smith, P. K., Krohn, R. I., Hermanson. G. T., Mallia, A. K., Gartner, F. H., et al. (1985) Measurement of protein using bicinchoninic acid. Anal. Biochem. 150, 76−85
  42. Stadtman, E. R. (1993) Oxidation of free amino acids and amino acid residues in proteins by radiolysis and by metal-catalyzed reactions. Annu. Rev. Biochem. 62, 797−821 https://doi.org/10.1146/annurev.bi.62.070193.004053
  43. Towbin, H., Staehelin, T., and Gordon, J. (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc. Natl. Acad. Sci. USA 76, 4350−4354
  44. Wang, X. and Pielak, G. J. (1999) Equilibrium thermodynamics of a physiologically-relevant heme-protein complex. Biochemistry 38, 16876−16881 https://doi.org/10.1021/bi992005i
  45. Zou, H., Li, Y., Liu, X., and Wang, X. (1999) An APAF-1- cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J. Biol. Chem. 274, 11549−11556 https://doi.org/10.1074/jbc.274.17.11549
  46. Zweier, J. L., Kuppusamy, P., Williams, R., Rayburn, B. K., Smith, D., et al. (1989) Measurement and characterization of postischemic free radical generation in the isolated perfused heart. J. Biol. Chem. 264, 18890−18895