Cell Biology and Toxicology

, Volume 25, Issue 4, pp 363–378

Acrolein toxicity involves oxidative stress caused by glutathione depletion in the yeast Saccharomyces cerevisiae

  • M. Kwolek-Mirek
  • S. Bednarska
  • G. Bartosz
  • T. Biliński


Exposure of yeast cells to allyl alcohol results in intracellular production of acrolein. The toxicity of so formed acrolein involves oxidative stress, as (1) strains deficient in antioxidant defense are hypersensitive to allyl alcohol, (2) exposure to allyl alcohol increases the level of thiobarbituric-acid-reactive substances and decreases glutathione level in the cells, (3) hypoxic and anoxic atmosphere and antioxidants protect against allyl alcohol toxicity, and (4) allyl alcohol causes activation of Yap1p. No increased formation of reactive oxygen species was detected in cells exposed to allyl alcohol, so oxidative stress is due to depletion of cellular thiols and thus alteration in the redox state of yeast cells.


Yeast Saccharomyces cerevisiae Acrolein Allyl alcohol Oxidative stress Glutathione 



allyl alcohol




alcohol dehydrogenase


dihydrodichlorofluorescein diacetate






reactive oxygen species


  1. Azevedo D, Tacnet F, Delaunay A, Rodrigues-Pousada C, Toledano MB. Two redox centers within Yap1 for H2O2 and thiol-reactive chemicals signaling. Free Radic Biol Med 2003;35:889–902.PubMedCrossRefGoogle Scholar
  2. Bakker BM, Bro C, Kotter P, Luttik MA, van Dijken JP, Pronk JT. The mitochondrial alcohol dehydrogenase ADH3p is involved in a redox shuttle in Saccharomyces cerevisiae. J Bacteriol 2000;182:4730–7.PubMedCrossRefGoogle Scholar
  3. Benov L, Sztejnberg L, Fridovich I. Critical evaluation of the use of hydroethidine as a measure of superoxide anion radical. Free Radic Biol Med 1998;25:826–31.PubMedCrossRefGoogle Scholar
  4. Bilinski T, Lukaszkiewicz J, Sledziewski A. Demonstration of anaerobic catalase synthesis in the cz1 mutant of Saccharomyces cerevisiae. Biochem Biophys Res Commun 1978;83:1225–33.PubMedCrossRefGoogle Scholar
  5. Bilinski T, Litwinska J, Blaszczynski M, Bajus A. Superoxide dismutase deficiency and the toxicity of the products of autooxidation of polyunsaturated fatty acids in yeast. Biochim Biophys Acta 1989;1001:102–6.PubMedGoogle Scholar
  6. Biliński T, Kwolek M, Sas E, Krynicka M, Koziol S, Owsiak-Teleon A, et al. A novel test for identifying genes involved in aldehyde detoxification in the yeast. Increased sensitivity of superoxide-deficient yeast to aldehydes and their metabolic precursors. Biofactors 2005;24:59–65.PubMedCrossRefGoogle Scholar
  7. Delaunay A, Pflieger D, Barrault M, Vinh J, Toledano MB. A thiol peroxidase is an H2O2 receptor and redox-transducer in gene activation. Cell 2002;111:471–81.PubMedCrossRefGoogle Scholar
  8. Drakulic T, Temple MD, Guido R, Jarolim S, Breitenbach M, Attfield PV, et al. Involvement of oxidative stress response genes in redox homeostasis, the level of reactive oxygen species, and ageing in Saccharomyces cerevisiae. FEMS Yeast Res 2005;5:1215–28.PubMedCrossRefGoogle Scholar
  9. Enoiu M, Herber R, Wennig R, Marson C, Bodaud H, Leroy P, et al. gamma-Glutamyltranspeptidase-dependent metabolism of 4-hydroxynonenal-glutathione conjugate. Arch Biochem Biophys 2002;397:18–27.PubMedCrossRefGoogle Scholar
  10. Esterbauer H, Schaur RJ, Zollner H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 1991;11:81–128.PubMedCrossRefGoogle Scholar
  11. Falcon-Perez JM, Mazon MJ, Molano J, Eraso P. Functional domain analysis of yeast ABC transporter Ycf1p by site-directed mutagenesis. J Biol Chem 1999;274:23584–90.PubMedCrossRefGoogle Scholar
  12. Grant CM. Role of the glutathione/glutaredoxin and thioredoxin systems in yeast growth and response to stress conditions. Mol Microbiol 2001;39:533–41.PubMedCrossRefGoogle Scholar
  13. Howlett NG, Avery SV. Induction of lipid peroxidation during heavy metal stress in Saccharomyces cerevisiae and influence of plasma membrane fatty acid unsaturation. Appl Environ Microbiol 1997;63:2971–6.PubMedGoogle Scholar
  14. Ikner A, Shiozaki K. Yeast signaling pathways in the oxidative stress response. Mutation Res 2005;569:13–27.PubMedGoogle Scholar
  15. Izawa S, Maeda K, Sugiyama K, Mano J, Inoue Y. Thioredoxin deficiency causes the constitutive activation of Yap1, an AP-1-like transcription factor in Saccharomyces cerevisiae. J Biol Chem 1999;274:28459–65.PubMedCrossRefGoogle Scholar
  16. Koziol S, Zagulski M, Bilinski T, Bartosz G. Antioxidants protect the yeast Saccharomyces cerevisiae against hypertonic stress. Free Radic Res 2005;39:365–71.PubMedCrossRefGoogle Scholar
  17. Kuge S, Jones N, Nomoto A. Regulation of yAP-1 nuclear localization in response to oxidative stress. EMBO J 1997;16:1710–20.PubMedCrossRefGoogle Scholar
  18. Kuhry JG, Fonteneau P, Duportail G, Maechling C, Laustriat G. TMA-DPH: a suitable fluorescence polarization probe for specific plasma membrane fluidity studies in intact living cells. Cell Biophys 1983;5:129–40.PubMedGoogle Scholar
  19. Lemar KM, Passa O, Aon MA, Cortassa S, Műller CT, Plummer S, et al. Allyl alcohol and garlic (Allium sativum) extract produce oxidative stress in Candida albicans. Microbiology 2005;151:3257–65.PubMedCrossRefGoogle Scholar
  20. Leskovac V, Trivic S, Anderson BM. Use of competitive dead-end inhibitors to determine the chemical mechanism of action of yeast alcohol dehydrogenase. Mol Cell Biochem 1998;178:219–27.PubMedCrossRefGoogle Scholar
  21. Leskovac V, Trivic S, Pericin D. The three zinc-containing alcohol dehydrogenases from baker’s yeast, Saccharomyces cerevisiae. FEMS Yeast Res 2002;2:481–94.PubMedGoogle Scholar
  22. Li ZS, Szczypka M, Lu YP, Thiele DJ, Rea PA. The yeast cadmium factor protein (YCF1) is a vacuolar glutathione S-conjugate pump. J Biol Chem 1996;271:6509–17.PubMedCrossRefGoogle Scholar
  23. López-Mirabal HR, Thorsen M, Kielland-Brandt Morten C, Toledano MB, Winther JR. Cytoplasmic glutathione redox status determines survival upon exposure to the thiol-oxidant 4,4¢-dipyridyl disulfide. FEMS Yeast Res 2007;7:391–403.PubMedCrossRefGoogle Scholar
  24. Nair S, Singh SV, Krishan A. Flow cytometric monitoring of glutathione content and anthracycline retention in tumor cells. Cytometry 1991;12:336–42.PubMedCrossRefGoogle Scholar
  25. Okazaki S, Naganuma A, Kuge S. Peroxiredoxin-mediated redox regulation of the nuclear localization of Yap1, a transcription factor in budding yeast. Antioxid Redox Signal 2005;7:327–34.PubMedCrossRefGoogle Scholar
  26. Penninckx MJ. An overview on glutathione in Saccharomyces versus non-conventional yeasts. FEMS Yeast Res 2002;2:295–305.PubMedGoogle Scholar
  27. Rice-Evans CA, Diplock AT, Symons MCR. Techniques in free radical research. Amsterdam: Elsevier; 1991.Google Scholar
  28. Trotter EW, Collinson EJ, Dawes IW, Grant CM. Old yellow enzymes protect against acrolein toxicity in the yeast Saccharomyces cerevisiae. Appl Environ Microbiol 2006;72:4885–92.PubMedCrossRefGoogle Scholar
  29. Turton HE, Dawes IW, Grant CM. Saccharomyces cerevisiae exhibits a yAP-1-mediated adaptive response to malondialdehyde. J Bacteriol 1997;179:1096–101.PubMedGoogle Scholar
  30. Uchida K, Kanematsu M, Morimitsu Y, Osawa T, Noguchi N, Niki E. Acrolein is a product of lipid peroxidation reaction. Formation of free acrolein and its conjugate with lysine residueas in oxidized low density lipoproteins. J Biol Chem 1998a;273:16058–66.PubMedCrossRefGoogle Scholar
  31. Uchida K, Kanematsu M, Sakai K, Matsuda T, Hattori N, Mizuno Y, et al. Protein-bound acrolein: Potential markers for oxidative stress. Proc Natl Acad Sci USA 1998b;95:4882–7.PubMedCrossRefGoogle Scholar
  32. Wills C, Hom D. An efficient selection producing structural gene mutants of yeast alcohol dehydrogenase resistant to pyrazole. Genetics 1988;119:791–5.PubMedGoogle Scholar
  33. Wills C, Phelps J. Functional mutants of yeast alcohol dehydrogenase affecting kinetics, cellular redox balance and electrophoretic mobility. Biochem Genet 1978;16:415–32.PubMedCrossRefGoogle Scholar
  34. Yang M, Schaich KM. Factors affecting DNA damage caused by lipid hydroperoxides and aldehydes. Free Radic Biol Med 1996;20:225–36.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • M. Kwolek-Mirek
    • 1
  • S. Bednarska
    • 1
  • G. Bartosz
    • 1
    • 2
  • T. Biliński
    • 1
  1. 1.Department of Biochemistry and Cell BiologyUniversity of RzeszówRzeszówPoland
  2. 2.Department of Molecular BiophysicsUniversity of ŁódźŁódźPoland

Personalised recommendations