1887

Abstract

Oxidative damage in microbial cells occurs during exposure to the toxic metal chromium, but it is not certain whether such oxidation accounts for the toxicity of Cr. Here, a Δ mutant (defective for the Cu,Zn-superoxide dismutase) was found to be hypersensitive to Cr(VI) toxicity under aerobic conditions, but this phenotype was suppressed under anaerobic conditions. Studies with cells expressing a Sod1p variant (Sod1) showed that the superoxide dismutase activity rather than the metal-binding function of Sod1p was required for Cr resistance. To help identify the macromolecular target(s) of Cr-dependent oxidative damage, cells deficient for the reduction of phospholipid hydroperoxides (Δ and Δ/Δ/Δ) and for the repair of DNA oxidation (Δ and Δ/Δ) were tested, but were found not to be Cr-sensitive. In contrast, Δ (Δ) and Δ (Δ) mutants defective for peptide methionine sulfoxide reductase (MSR) activity exhibited a Cr sensitivity phenotype, and cells overexpressing these enzymes were Cr-resistant. Overexpression of MSRs also suppressed the Cr sensitivity of Δ cells. The inference that protein oxidation is a primary mechanism of Cr toxicity was corroborated by an observed ∼20-fold increase in the cellular levels of protein carbonyls within 30 min of Cr exposure. Carbonylation was not distributed evenly among the expressed proteins of the cells; certain glycolytic enzymes and heat-shock proteins were specifically targeted by Cr-dependent oxidative damage. This study establishes an oxidative mode of Cr toxicity in , which primarily involves oxidative damage to cellular proteins.

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2005-06-01
2019-11-15
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References

  1. Ackerley, D. F., Gonzalez, C. F., Keyhan, M., Blake, R. & Matin, A. ( 2004; ). Mechanism of chromate reduction by the Escherichia coli protein, NfsA, and the role of different chromate reductases in minimizing oxidative stress during chromate reduction. Environ Microbiol 6, 851–860.[CrossRef]
    [Google Scholar]
  2. Aiyar, J., Berkovits, H. J., Floyd, R. A. & Wetterhahn, K. E. ( 1991; ). Reaction of chromium(VI) with glutathione or with hydrogen peroxide: identification of reactive intermediates and their role in chromium(VI)-induced DNA damage. Environ Health Perspect 92, 53–62.[CrossRef]
    [Google Scholar]
  3. Ausubel, F., Brent, R., Kingston, R. E., Moore, D. D., Seidman, J. G., Smith, J. A. & Struhl, K. ( 2004; ). Current Protocols in Molecular Biology. New York: Wiley.
  4. Avery, A. M. & Avery, S. V. ( 2001; ). Saccharomyces cerevisiae expresses three phospholipid hydroperoxide glutathione peroxidases. J Biol Chem 276, 33730–33735.[CrossRef]
    [Google Scholar]
  5. Avery, A. M., Willetts, S. A. & Avery, S. V. ( 2004; ). Genetic dissection of the phospholipid hydroperoxidase activity of yeast Gpx3 reveals its functional importance. J Biol Chem 279, 46652–46658.[CrossRef]
    [Google Scholar]
  6. Avery, S. V. ( 2001; ). Metal toxicity in yeasts and the role of oxidative stress. Adv Appl Microbiol 49, 111–142.
    [Google Scholar]
  7. Avery, S. V., Howlett, N. G. & Radice, S. ( 1996; ). Copper toxicity towards Saccharomyces cerevisiae: dependence on plasma-membrane fatty acid composition. Appl Environ Microbiol 62, 3960–3966.
    [Google Scholar]
  8. Cabiscol, E., Piulats, E., Echave, P., Herrero, E. & Ros, J. ( 2000; ). Oxidative stress promotes specific protein damage in Saccharomyces cerevisiae. J Biol Chem 275, 27393–27398.
    [Google Scholar]
  9. Cervantes, C., Campos-Garcia, J., Devars, S., Gutierrez-Corona, F., Loza-Tavera, H., Torres-Guzman, J. C. & Moreno-Sanchez, R. ( 2001; ). Interactions of chromium with microorganisms and plants. FEMS Microbiol Rev 25, 335–347.[CrossRef]
    [Google Scholar]
  10. Cheng, L., Liu, S. J. & Dixon, K. ( 1998; ). Analysis of repair and mutagenesis of chromium-induced DNA damage in yeast, mammalian cells, and transgenic yeast. Environ Health Perspect Suppl 4 106, 1027–1032.[CrossRef]
    [Google Scholar]
  11. Ciriolo, M. R., Civitareale, P., Carri, M. T., Demartino, A., Galiazzo, F. & Rotilio, G. ( 1994; ). Purification and characterization of Ag,Zn-superoxide dismutase from Saccharomyces cerevisiae exposed to silver. J Biol Chem 269, 25783–25787.
    [Google Scholar]
  12. Costa, W. M. V., Amorim, M. A., Quintanilha, A. & Moradas-Ferreira, P. ( 2002; ). Hydrogen peroxide-induced carbonylation of key metabolic enzymes in Saccharomyces cerevisiae: the involvement of the oxidative stress response regulators Yap1 and Skn7. Free Rad Biol Med 33, 1507–1515.[CrossRef]
    [Google Scholar]
  13. Culotta, V. C., Joh, H. D., Lin, S. J., Slekar, K. H. & Strain, J. ( 1995; ). A physiological role for Saccharomyces cerevisiae copper/zinc superoxide dismutase in copper buffering. J Biol Chem 270, 29991–29997.[CrossRef]
    [Google Scholar]
  14. Dayan, A. D. & Paine, A. J. ( 2001; ). Mechanisms of chromium toxicity, carcinogenicity and allergenicity: review of the literature from 1985 to 2000. Human Exp Toxicol 20, 439–451.[CrossRef]
    [Google Scholar]
  15. Delaunay, A., Pflieger, D., Barrault, M. B., Vinh, J. & Toledano, M. B. ( 2002; ). A thiol peroxidase is an H2O2 receptor and redox-transducer in gene activation. Cell 111, 471–481.[CrossRef]
    [Google Scholar]
  16. Feng, W. Y., Li, B., Liu, J., Chai, Z. F., Zhang, P. Q., Gao, Y. X. & Zhao, J. J. ( 2003; ). Study of chromium-containing proteins in subcellular fractions of rat liver by enriched stable isotopic tracer technique and gel filtration chromatography. Anal Bioanal Chem 375, 363–368.
    [Google Scholar]
  17. Fernandes, M. A. S., Santos, M. S., Alpoim, M. C., Madeira, V. M. C. & Vicente, J. A. F. ( 2002; ). Chromium(VI) interaction with plant and animal mitochondrial bioenergetics: a comparative study. J Biochem Mol Toxicol 16, 53–63.[CrossRef]
    [Google Scholar]
  18. Gadd, G. M. ( 1992; ). Metals and microorganisms – a problem of definition. FEMS Microbiol Lett 100, 197–203.[CrossRef]
    [Google Scholar]
  19. Gietz, R. D. & Woods, R. A. ( 2002; ). Transformation of yeast by lithium acetate/single-stranded carrier DNA/polyethylene glycol method. Methods Enzymol 350, 87–96.
    [Google Scholar]
  20. Godon, C., Lagniel, G., Lee, J., Buhler, J. M., Kieffer, S., Perrot, R., Boucherie, H., Toledano, M. B. & Labarre, J. ( 1998; ). The H2O2 stimulon in Saccharomyces cerevisiae. J Biol Chem 273, 22480–22489.[CrossRef]
    [Google Scholar]
  21. Grune, T., Reinheckel, T. & Davies, K. J. A. ( 1997; ). Degradation of oxidized proteins in mammalian cells. Faseb J 11, 526–534.
    [Google Scholar]
  22. Halliwell, B. & Gutteridge, J. M. C. ( 1999; ). Free Radicals in Biology and Medicine, 3rd edn. Oxford: Oxford University Press.
  23. Haracska, L., Yu, S. L., Johnson, R. E., Prakash, L. & Prakash, S. ( 2000; ). Efficient and accurate replication in the presence of 7,8-dihydro-8-oxoguanine by DNA polymerase ε. Nat Genet 25, 458–461.[CrossRef]
    [Google Scholar]
  24. Henderson, G. ( 1989; ). A comparison of the effects of chromate, molybdate and cadmium oxide on respiration in the yeast Saccharomyces cerevisiae. Biol Met 2, 83–88.[CrossRef]
    [Google Scholar]
  25. Hodges, N. J. & Chipman, J. K. ( 2002; ). Down-regulation of the DNA-repair endonuclease 8-oxo-guanine DNA glycosylase 1 (hOGG1) by sodium dichromate in cultured human A549 lung carcinoma cells. Carcinogenesis 23, 55–60.[CrossRef]
    [Google Scholar]
  26. Howlett, N. G. & Avery, S. V. ( 1997; ). Induction of lipid peroxidation during heavy metal stress in Saccharomyces cerevisiae and influence of plasma membrane fatty acid unsaturation. Appl Environ Microbiol 63, 2971–2976.
    [Google Scholar]
  27. Jamieson, D. J. ( 1998; ). Oxidative stress responses of the yeast Saccharomyces cerevisiae. Yeast 14, 1511–1527.[CrossRef]
    [Google Scholar]
  28. Kasprzak, K. S. ( 2002; ). Oxidative DNA and protein damage in metal-induced toxicity and carcinogenesis. Free Rad Biol Med 32, 958–967.[CrossRef]
    [Google Scholar]
  29. Kim, Y. H., Berry, A. H., Spencer, D. S. & Stites, W. E. ( 2001; ). Comparing the effect on protein stability of methionine oxidation versus mutagenesis: steps toward engineering oxidative resistance in proteins. Prot Eng 14, 343–347.[CrossRef]
    [Google Scholar]
  30. Koc, A., Gasch, A. P., Rutherford, J. C., Kim, H. Y. & Gladyshev, V. N. ( 2004; ). Methionine sulfoxide reductase regulation of yeast lifespan reveals reactive oxygen species-dependent and -independent components of aging. Proc Natl Acad Sci U S A 101, 7999–8004.[CrossRef]
    [Google Scholar]
  31. Kryukov, G. V., Kumar, R. A., Koc, A., Sun, Z. H. & Gladyshev, V. N. ( 2002; ). Selenoprotein R is a zinc-containing stereo-specific methionine sulfoxide reductase. Proc Natl Acad Sci U S A 99, 4245–4250.[CrossRef]
    [Google Scholar]
  32. Levine, R. L., Moskovitz, J. & Stadtman, E. R. ( 2000; ). Oxidation of methionine in proteins: roles in antioxidant defense and cellular regulation. IUBMB Life 50, 301–307.[CrossRef]
    [Google Scholar]
  33. Lu, Y., Roe, J. A., Bender, C. J., Peisach, J., Banci, L., Bertini, I., Gralla, E. B. & Valentine, J. S. ( 1996; ). New type 2 copper-cysteinate proteins. Copper site histidine-to-cysteine mutants of yeast copper-zinc superoxide dismutase. Inorg Chem 35, 1692–1700.[CrossRef]
    [Google Scholar]
  34. Luo, H., Lu, Y., Shi, X., Mao, Y. & Delal, N. S. ( 1996; ). Chromium (IV)-mediated Fenton-like reaction causes DNA damage: implication to genotoxicity of chromate. Ann Clin Lab Sci 26, 185–191.
    [Google Scholar]
  35. Moradas-Ferreira, P., Costa, V., Piper, P. & Mager, W. ( 1996; ). The molecular defences against reactive oxygen species in yeast. Mol Microbiol 19, 651–658.[CrossRef]
    [Google Scholar]
  36. Nguyen-Nhu, N. T. & Knoops, B. ( 2002; ). Alkyl hydroperoxide reductase 1 protects Saccharomyces cerevisiae against metal ion toxicity and glutathione depletion. Toxicol Lett 135, 219–228.[CrossRef]
    [Google Scholar]
  37. Nishida, C. R., Gralla, E. B. & Valentine, J. S. ( 1994; ). Characterization of three yeast copper-zinc superoxide dismutase mutants analogous to those coded for in familial amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A 91, 9906–9910.[CrossRef]
    [Google Scholar]
  38. O'Brien, T., Xu, J. & Patierno, S. R. ( 2001; ). Effects of glutathione on chromium-induced DNA crosslinking and DNA polymerase arrest. Mol Cell Biochem 222, 173–182.[CrossRef]
    [Google Scholar]
  39. O'Brien, T. J., Fornsaglio, J. L., Ceryak, S. & Patierno, S. R. ( 2002; ). Effects of hexavalent chromium on the survival and cell cycle distribution of DNA repair-deficient S. cerevisiae. DNA Repair 1, 617–627.[CrossRef]
    [Google Scholar]
  40. Pesti, M., Gazdag, Z., Emri, T., Farkas, N., Koosz, Z., Belagy, J. & Pocsi, I. ( 2002; ). Chromate sensitivity in fission yeast is caused by increased glutathione reductase activity and peroxide overproduction. J Basic Microbiol 42, 408–419.[CrossRef]
    [Google Scholar]
  41. Pourahmad, J. & O'Brien, P. J. ( 2001; ). Biological reactive intermediates that mediate chromium (VI) toxicity. Biol React Intermed VI Adv Exp Med Biol 500, 203–207.
    [Google Scholar]
  42. Ravichandran, V., Seres, T., Moriguchi, T., Thomas, J. A. & Johnston, R. B. ( 1994; ). S-thiolation of glyceraldehyde-3-phosphate dehydrogenase induced by the phagocytosis-associated respiratory burst in blood monocytes. J Biol Chem 269, 25010–25015.
    [Google Scholar]
  43. Requena, J. R., Chao, C. C., Levine, R. L. & Stadtman, E. R. ( 2001; ). Glutamic and aminoadipic semialdehydes are the main carbonyl products of metal-catalyzed oxidation of proteins. Proc Natl Acad Sci U S A 98, 69–74.[CrossRef]
    [Google Scholar]
  44. Reynolds, M., Peterson, E., Quievryn, G. & Zhitkovich, A. ( 2004; ). Human nucleotide excision repair efficiently removes chromium-DNA phosphate adducts and protects cells against chromate toxicity. J Biol Chem 279, 30419–30424.[CrossRef]
    [Google Scholar]
  45. Shanmuganathan, A., Avery, S. V., Willetts, S. A. & Houghton, J. E. ( 2004; ). Copper-induced oxidative stress in Saccharomyces cerevisiae targets enzymes of the glycolytic pathway. FEBS Lett 556, 253–259.[CrossRef]
    [Google Scholar]
  46. Shenton, D. & Grant, C. M. ( 2003; ). Protein S-thiolation targets glycolysis and protein synthesis in response to oxidative stress in the yeast Saccharomyces cerevisiae. Biochem J 374, 513–519.[CrossRef]
    [Google Scholar]
  47. Shrivastava, H. Y. & Nair, B. U. ( 2000; ). Protein degradation by peroxide catalyzed by chromium (III): role of coordinated ligand. Biochem Biophys Res Commun 270, 749–754.[CrossRef]
    [Google Scholar]
  48. Shrivastava, H. Y. & Nair, B. U. ( 2004; ). Fluorescence resonance energy transfer from tryptophan to a chromium(III) complex accompanied by non-specific cleavage of albumin: a step forward towards the development of a novel photoprotease. J Inorg Biochem 98, 991–994.[CrossRef]
    [Google Scholar]
  49. Sumner, E. R., Avery, A. M., Houghton, J. E., Robins, R. A. & Avery, S. V. ( 2003; ). Cell cycle- and age-dependent activation of Sod1p drives the formation of stress-resistant cell subpopulations within clonal yeast cultures. Mol Microbiol 50, 857–870.[CrossRef]
    [Google Scholar]
  50. Swanson, R. L., Morey, N. J., Doetsch, P. W. & Jinks-Robertson, S. ( 1999; ). Overlapping specificities of base excision repair, nucleotide excision repair, recombination, and translesion synthesis pathways for DNA base damage in Saccharomyces cerevisiae. Mol Cell Biol 19, 2929–2935.
    [Google Scholar]
  51. Wei, J. P. J., Srinivasan, C., Han, H., Valentine, J. S. & Gralla, E. B. ( 2001; ). Evidence for a novel role of copper-zinc superoxide dismutase in zinc metabolism. J Biol Chem 276, 44798–44803.[CrossRef]
    [Google Scholar]
  52. White, C., Sharman, A. K. & Gadd, G. M. ( 1998; ). An integrated microbial process for the bioremediation of soil contaminated with toxic metals. Nat Biotechnol 16, 572–575.[CrossRef]
    [Google Scholar]
  53. Willetts, S. A. ( 2004; ). Genetic and genomic approaches to understanding metal toxicity in Saccharomyces cerevisiae. PhD thesis, University of Nottingham.
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