Skip to main content
Log in

Moderate intermittent hypoxia/hyperoxia: implication for correction of mitochondrial dysfunction

  • Research Article
  • Published:
Central European Journal of Biology

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

The purpose of this study was to appreciate the acute hypoxia-induced mitochondrial oxidative damage development and the role of adaptation to hypoxia/hyperoxia (H/H) in correction of mitochondrial dysfunction. It was demonstrated that long-term sessions of moderate H/H [5 cycles of 5 min hypoxia (10% O2 in N2) alternated with 5 min hyperoxia (30% O2 in N2) daily for two weeks]_attenuated basal and Fe2+/ascorbate-induced lipid peroxidation (LPO) as well as production of carbonyl proteins and H2O2 in liver mitochondria of rats exposed to acute severe hypoxia (7% O2 in N2, 60 min) in comparison with untreated animals. It was shown that H/H increases the activity of glutathione peroxidase (GPx), reduces hyperactivation of Mn-SOD, and decreases Cu,Zn-SOD activity as compared with untreated rats. It has been suggested that the induction of Mn-SOD protein expression and the coordinated action of Mn-SOD and GPx could be the mechanisms underlying protective effects of H/H, which promote the correction of the acute hypoxia-induced mitochondrial dysfunction. The increase in Mn-SOD protein synthesis without changes in Mn-SOD mRNA level under H/H pretreatment indicates that the Mn-SOD activity is most likely dependent on its posttranslational modification or on the redox state of liver mitochondria.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Li C., Jackson R.M., Reactive species mechanisms of cellular hypoxia-reoxygenation injury, Am. J. Physiol., 2002, 282, C227–C241

    CAS  Google Scholar 

  2. Cadenas E., Mitochondrial free radical production and cell signaling, Mol. Aspects Med., 2004, 25, 17–26

    Article  PubMed  CAS  Google Scholar 

  3. Fujishiro N., Endo Y., Warashina A., Inoue M., Mechanisms for hypoxia detection in O2-sensitive cells, Jap. J. Physiol., 2004, 54, 109–123

    Article  CAS  Google Scholar 

  4. Chandel N., Budinger G.,. The cellular basis for diverse responses to oxygen, Free Radic. Biol. Med., 2007, 42, 165–174

    Article  PubMed  CAS  Google Scholar 

  5. Bartosz G., Reactive oxygen species: destroyers or messengers?, Biochem. Pharmacol., 2009, 77, 1303–1315

    Article  PubMed  CAS  Google Scholar 

  6. Poyton R., Ball K., Castello P., Mitochondrial generation of free radicals and hypoxic signaling, Trends Endocrinol. Metabol., 2009, 20, 332–340

    Article  CAS  Google Scholar 

  7. Okado-Matsumoto A., Fridovich I. Subcellular distribution of superoxide dismutase in rat liver, J. Biol Chem., 2001, 276, 38388–38393

    Article  PubMed  CAS  Google Scholar 

  8. Yu B.P., Cellular defenses against damage from reactive oxygen species, Physiol Rev., 1994, 74, 139–162

    PubMed  CAS  Google Scholar 

  9. Clanton T.L., Klawitter P.F., Physiological and Genomic Consequences of Intermittent Hypoxia. Invited Review: Adaptive responses of skeletal muscle to intermittent hypoxia: the known and the unknown, J. Appl. Physiol., 2001, 90, 2476–2487

    PubMed  CAS  Google Scholar 

  10. Vogt M., Puntschart, A., Geiser, J., Zuleger, C., Billeter, R., Hoppeler, H. Molecular adaptations in human skeletal muscle to endurance training under hypoxic conditions., J. Appl. Physiol., 2001, 91, 173–182

    PubMed  CAS  Google Scholar 

  11. Sharp F., Ran R., Lu A., Tang Y., Strauss K., Glass T., et al., Hypoxic preconditioning protects against ischemic brain injury, Neuro Rx®., 2004, 1, 26–35

    Article  Google Scholar 

  12. Lee E., Smith W., Quach H., Jones B., Moderate hyperoxia (40%) increases antioxidant levels in mouse tissue, J. Surg. Res., 2005, 127, 80–84

    Article  PubMed  CAS  Google Scholar 

  13. Gonchar O., Effect of intermittent hypoxia different regimes on mitochondrial lipid peroxidation and glutathione-redox balance in stressed rats, Cent. Eur. J. Biol., 2008, 3, 233–242

    Article  CAS  Google Scholar 

  14. Gonchar O., Mankovskaya I., Effect of moderate hypoxia/reoxygenation on mitochondrial adaptation to acute severe hypoxia, Acta Biol. Hung., 2009. 60, 185–194

    Article  PubMed  Google Scholar 

  15. Bigdeli M., Preconditioning with prolonged normobaric hyperoxia induces ischemic tolerance partly by upregulation of antioxidant enzymes in rat brain tissue, Brain Res., 2009, 1260, 47–54

    Article  PubMed  CAS  Google Scholar 

  16. Lukyanova L.D., Novel approach to the understanding of molecular mechanisms of adaptation to hypoxia, In: Hargens A., Takeda N., Singal P. (Eds.), Adaptation Biology and Medicine, Vol. 4., Current Concepts, New Delhi: Narosa, 2005

    Google Scholar 

  17. Sazontova T.G., Arhipenko Y.V., Intermittent hypoxia in resistance of cardiac membrane structures:role of reactive oxygen species and redox signaling, In: Lei Hi, Serebrovskaya T. (Eds.), Intermittent hypoxia: from molecular mechanisms to clinical Application, Nova Science Publishers, Inc. New York, 2009

    Google Scholar 

  18. Bonfigli A., Colafarina S., Falone S., Di Giulio C., Di Ilio C., Amicarelli F., High levels of antioxidant enzymatic defence assure good protection against hypoxic stress in spontaneously diabetic rats, The Int. J. Biochem. Cell Biol., 2006, 38, 2196–2208

    Article  CAS  Google Scholar 

  19. Shan X., Chi L., Ke Y., Luo C., Qian S., Gozal D., et al., Manganese superoxide dismutase protects mouse cortical neurons from chronic intermittent hypoxia-mediated oxidative damage, Neurobiol. Dis., 2007, 28, 206–215

    Article  PubMed  CAS  Google Scholar 

  20. Pardo M., Tirosh, O., Protective signaling effect of manganese superoxide dismutase in hypoxia-reoxygenation of hepatocytes, Free Radic. Res., 2009, 43, 1225–1239

    Article  PubMed  CAS  Google Scholar 

  21. Jonson D., Lardy H., Isolation of liver and kidney mitochondria, Methods Enzymol., 1967, 10, 94–96

    Article  Google Scholar 

  22. Buege J., Aust S., Microsomal lipid peroxidation, Methods Enzymol., 1978, 32, 302–308

    Article  Google Scholar 

  23. Levine R.L., Garland D., Oliver C.N., Amici A., Climent I., Lenz A., et al., Determination of carbonyl content in oxidatively modified proteins, Methods Enzymol., 1990, 186, 464–478

    Article  PubMed  CAS  Google Scholar 

  24. Huwiler M., Kohler H. Pseudo-catalytic degradation of hydrogen peroxide in the lactoperoxidase/H2O2/ iodide system, Eur. J. Biochem., 1984, 141, 69–74

    Article  PubMed  CAS  Google Scholar 

  25. Misra H., Fridovich I., The role of superoxide anion in the autoxidation of epinephrine and a simple assay superoxide dismutase, J. Biol. Chem., 1972, 247, 3170–3175

    PubMed  CAS  Google Scholar 

  26. Flohe L., Gunzler W.A., Assay of glutathione peroxidase, Methods Enzymol., 1984, 105, 114–120

    Article  PubMed  CAS  Google Scholar 

  27. Laemmli U., Cleavage of structural proteins during the assembly of the head of bacteriophage T4, Nature, 1970, 227, 680–685

    Article  PubMed  CAS  Google Scholar 

  28. Dean R.T., Fu S., Stocker R., Davies M.J., Biochemistry and pathology of radical-mediated protein oxidation, Biochem J., 1997, 324, 1–18

    PubMed  CAS  Google Scholar 

  29. Stadtman E.R., Berlett B.S., Resctive oxygenmediated protein oxidation in aging and disease, Drug Metab. Rev., 1998, 30, 225–243

    Article  PubMed  CAS  Google Scholar 

  30. Berlett B.S., Stadtman E.R. Protein oxidation in aging, disease, and oxidative stress, J Biol. Chem., 1997, 272, 20313–20316

    Article  PubMed  CAS  Google Scholar 

  31. Amstad P., Moret R., Cerutti P., Glutathione peroxidase compensates for the hypersensitivity of Cu,Zn-superoxide dismutase overproducers to oxidant stress, J. Biol. Chem., 1994, 269, 1606–1609

    PubMed  CAS  Google Scholar 

  32. Kato H., Kogure K., Araki T., Liu X., Keto K., Itoyama Y., Immunohistochemical localization of superoxide dismutase in the hippocampus following ischemia in a gerbil model of ischemic tolerance, J. Cereb. Blood Metab., 1995, 15, 60–70

    Article  CAS  Google Scholar 

  33. Fridovich I., Superoxide dismutases, Biochim. Biophys Acta., 1975, 877, 147–159

    Google Scholar 

  34. Yamakura F., Kawasaki H., Post-translational modifications of superoxide dysmutase, Biochim. Biophys. Acta., 2010, 1804, 318–325

    Article  PubMed  CAS  Google Scholar 

  35. Ho Y., Dey M., Crapo J., Antioxidant enzyme expression in rat lungs during hyperoxia, Am. J. Physiol., 1996, 270, L810–L818

    PubMed  CAS  Google Scholar 

  36. Shen C., Lee J., Su C., Wang D., Chen C., Hypoxia and reoxygenation of the lung tissues induced mRNA expressions of superoxide dismutase and catalase and interventions from different antioxidants, Transplant Proc., 2008, 40, 182–184

    Google Scholar 

  37. Oh-Ishi S., Kitzaki T., Yamashita H., Nagata N., Suzuki K., Taniguchi N., et al., Alterations of superoxide dismutase iso-enzyme activity, content, and mRNA expression with aging in rat skeletal muscle, Mech. Aging Dev., 1996, 84, 65–76

    Article  Google Scholar 

  38. Gonchar O., Mankovska. I., Activity and expression of the antioxidant enzyme MnSOD in the mitochondria during prolonged hypoxia/hyperoxia exposure, Int. J. Biol Chem., 2011, 5, 342–351

    Article  CAS  Google Scholar 

  39. Gonchar O., Mankovskaya I., Antioxidant system in adaptation to intermittent hypoxia, J. Biol. Sci., 2010, 10, 545–554

    Article  CAS  Google Scholar 

  40. Sen C., Packer L., Antioxidant and redox regulation of gene transcription, FASEB J., 1996, 10, 709–720

    PubMed  CAS  Google Scholar 

  41. Haddad J.J., Antioxidant and prooxidant mechanisms in the regulation of redox(y)-sensitive transcription factors, Cell Sign., 2002, 14, 879–897

    Article  CAS  Google Scholar 

  42. Jackson R., Parish G., Ho Y., Effects of hypoxia on expression of superoxide dismutases in cultured AT II cells and lung fibroblasts, Am. J. Physiol. Lung Cell Mol. Physiol., 1996, 271, L955–L962

    CAS  Google Scholar 

  43. Chen C., Tsai S., Ma M., Wu M., Hypoxic preconditioning enhanced renal superoxide dismutase levels in rats, J. Physiol., 2003, 552, 561–569

    Article  PubMed  CAS  Google Scholar 

  44. Saba H., Batinic-Haberle I., Munusamy S., Mitchell T., Lichti C., Megyesi J., et al., Manganese porphyrin reduce renal injury and mitochondrial damage during ischemia/reperfusion, Free Radic. Biol. Med., 2007, 42, 1571–1578

    Article  PubMed  CAS  Google Scholar 

  45. Keller J., Kindy M., Holtsberg F., Clai D., Yen H., Germeyer A., et al., Mitochondrial manganese superoxide dismutase prevents neural apoptosis and reduce ischemic brain injury: suppression of peroxynitrite production, lipid peroxidation, and mitochondrial dysfunction, J. Neurosci., 1998, 18, 687–697

    PubMed  CAS  Google Scholar 

  46. Cruthirds D., Novak L., Akhi K., Sanders P., Thompson J., MacMillan-Crow L., Mitochondrial targets of oxidative stress during renal ischemia/ reperfusion, Arch Biochem. Biophys., 2003, 412, 27–33

    Article  PubMed  CAS  Google Scholar 

  47. MacMillan-Crow L., Cruthirds D., Manganase superoxide dismutase in disease, Free Radic. Res., 2001, 34, 325–326

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Olga A. Gonchar.

About this article

Cite this article

Gonchar, O.A., Mankovska, I.N. Moderate intermittent hypoxia/hyperoxia: implication for correction of mitochondrial dysfunction. cent.eur.j.biol. 7, 801–809 (2012). https://doi.org/10.2478/s11535-012-0072-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2478/s11535-012-0072-x

Keywords

Navigation