Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Open Life Sciences

formerly Central European Journal of Biology

Editor-in-Chief: Ratajczak, Mariusz

1 Issue per year

IMPACT FACTOR 2016 (Open Life Sciences): 0.448

CiteScore 2016: 1.02

SCImago Journal Rank (SJR) 2016: 0.329
Source Normalized Impact per Paper (SNIP) 2016: 0.621

Open Access
See all formats and pricing
More options …
Volume 3, Issue 3


Volume 10 (2015)

Effects of intermittent hypoxia different regimes on mitochondrial lipid peroxidation and glutathione-redox balance in stressed rats

Olga Gonchar
  • Department of Hypoxic States, Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, 01024, Kyiv, Ukraine
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2008-07-12 | DOI: https://doi.org/10.2478/s11535-008-0016-7


The purpose of this study was to compare the influence of two regimes of intermittent hypoxia (IH) [repetitive 5 cycles of 5 min hypoxia (7% O2 or 12% O2 in N2) followed by 15 min normoxia, daily for three weeks] on oxidative stress protective systems in liver mitochondria. To estimate the effectiveness of hypoxia adaptation at the early and late preconditioning period, we exposed rats to acute 6-h immobilization at the 1st and 45th days after cessation of IH. We showed that severity of hypoxic episodes during IH might initiate different adaptive programs. Moderate hypoxia during IH prevents mitochondrial glutathione pool depletion induced by immobilization stress, maintains GSH-redox cycle via activation of glutathione peroxidase, glutathione-S-transferase, glutathione reductase, NADP+-dependent isocitrate dehydrogenase, and increases Mn-SOD activity. Such regimen of hypoxic preconditioning caused the decrease of mitochondrial superoxide anion generation as well as of basal and stimulated in vitro lipid peroxidation and this protective effect remained for 45 days under renormoxic conditions. Hypoxic adaptation in a more severe regimen exerted beneficial effects on the mitochondrial antioxidant defense system only at its later phase.

Keywords: Intermittent hypoxia; Adaptation; Mitochondria; Lipid peroxidation; Glutathione; Glutathione enzymes; Antioxidant defense

  • [1] 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, Current Concepts, New Delhi: Narosa, 2005 Google Scholar

  • [2] 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., 2007, 90, 2476–2487 Google Scholar

  • [3] W.-Z. Zhu, Y. Xie, L. Chen, H.-T. Yang, Z.-N. Zhou, Intermittent high altitude hypoxia inhibits opening of mitochondrial permeability transition pores against reperfusion injury, J. Mol. Cell Cardiol., 2006, 40, 96–106 http://dx.doi.org/10.1016/j.yjmcc.2005.09.016CrossrefGoogle Scholar

  • [4] Vanden Hoek T.L., Becker L.B., Shao Z.H., Li C.Q., Schumacker P.T., Preconditioning in cardiomyocytes protects by attenuating oxidant stress at reperfusion, Circ. Res., 2000, 86, 541–548 Google Scholar

  • [5] Lin A.M., Dung S.W., Chen C.F., Ho L.T., Hypoxic preconditioning prevents cortical infarction by transient focal ischemia-reperfusion, Ann. N.Y. Acad. Sci., 2003, 993, 168–178 Google Scholar

  • [6] 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 http://dx.doi.org/10.1602/neurorx.1.1.26CrossrefGoogle Scholar

  • [7] Gonchar O., Effect of intermittent hypoxia on proand antioxidant balance in rat heart during high-intensity chronic exercise, Acta Physiol. Hung., 2005, 92, 211–220 http://dx.doi.org/10.1556/APhysiol.92.2005.3-4.3CrossrefGoogle Scholar

  • [8] Yamashita N., Nishida M., Hoshida S., Kuzuya T., Hori M., Taniguchi N., et al., Induction of manganase superoxide dismutase in rat cardiac myocytes increases tolerance to hypoxia 24 hours after preconditioning, J. Clin. Invest., 1994, 94, 2193–2199 http://dx.doi.org/10.1172/JCI117580CrossrefGoogle Scholar

  • [9] Zong P., Setty S., Sun W., Martinez R., Tune J., Ehrenburg I.V., et al., Intermittent hypoxic training protects canine myocardium from infarction, Exp. Biol. Med., 2004, 229, 806–812 Google Scholar

  • [10] Joyeux-Faure M., Stanke-Labesque F., Lefebvre B., Beguin P., Godin-Ribuot D., Ribuot C., et al., Chronic intermittent hypoxia increases infarction in the isolated rat heart, J. Appl. Physiol., 2005, 98, 1691–1696 http://dx.doi.org/10.1152/japplphysiol.01146.2004CrossrefGoogle Scholar

  • [11] Du G., Mouithys-Mickalad A., Sluse F., Generation of superoxide anion by mitochondria and impairment of their functions during anoxia and reoxygenation in vitro, Free Radic. Biol. Med., 1998, 25, 1066–1074 http://dx.doi.org/10.1016/S0891-5849(98)00148-8CrossrefGoogle Scholar

  • [12] Schild L., Reiser G., Oxidative stress is involved in the permeabilization of the inner membrane of brain mitochondria exposed to hypoxia/reoxygenation and low micromolar Ca2+, FEBS J., 2005, 272, 3593–3601 http://dx.doi.org/10.1111/j.1742-4658.2005.04781.xCrossrefGoogle Scholar

  • [13] Waypa G.B., Schumacker P.T., Hypoxic pulmonary vasoconstriction: redox events in oxygen sensing, J. Appl. Physiol., 2005, 98, 404–414 http://dx.doi.org/10.1152/japplphysiol.00722.2004CrossrefGoogle Scholar

  • [14] Schild L., Reinheckel T., Wiswedel I., Augustin W., Short-term impairment of energy production in isolated rat liver mitochondria by hypoxia/reoxygenation: involvement of oxidative protein modification, Biochem. J., 1997, 328, 205–210 Google Scholar

  • [15] Bell E., Emerling B., Chandel N., Mitochondrial regulation of oxygen sensing, Mitochondrion, 2005, 5, 322–332 http://dx.doi.org/10.1016/j.mito.2005.06.005CrossrefGoogle Scholar

  • [16] Jezek P., Hlavata L., Mitochondria in homeostasis of reactive oxygen species in cell, tissues, and organism, Int. J. Biochem. Cell Biol., 2005, 37, 2478–2503 http://dx.doi.org/10.1016/j.biocel.2005.05.013CrossrefGoogle Scholar

  • [17] Dickinson D.A., Forman H.J., Cellular glutathione and thiols metabolism, Biochem. Pharmacol., 2002, 64, 1019–1026 http://dx.doi.org/10.1016/S0006-2952(02)01172-3CrossrefGoogle Scholar

  • [18] Arrigo A.P., Gene expression and the thiol redox state, Free Radic. Biol. Med., 1999, 27, 936–944 http://dx.doi.org/10.1016/S0891-5849(99)00175-6CrossrefGoogle Scholar

  • [19] Vogel R., Wiesinger H., Hamprecht B., Dringen R., The regeneration of reduced glutathione in rat forebrain mitochondria identifies metabolic pathways providing the NADPH required, Neurosci. Lett., 1999, 275, 97–100 http://dx.doi.org/10.1016/S0304-3940(99)00748-XCrossrefGoogle Scholar

  • [20] Jo S., Son M., Koh H., Lee S., Song I., Kim Y., et al., Control of mitochondrial redox balance and cellular defense against oxidative damage by mitochondrial NADP+-dependent isocitrate dehydrogenase, J. Biol. Chem., 2001, 276, 16168–16176 http://dx.doi.org/10.1074/jbc.M010120200CrossrefGoogle Scholar

  • [21] Mansfield K., Simon M., Keith B., Hypoxic reduction in cellular glutathione levels requires mitochondrial reactive oxygen species, J. Appl. Physiol., 2004, 97, 1358–1366 http://dx.doi.org/10.1152/japplphysiol.00449.2004CrossrefGoogle Scholar

  • [22] Jonson D., Lardy H., Isolation of liver and kidney mitochondria, Methods Enzymol., 1967,10, 94–96 http://dx.doi.org/10.1016/0076-6879(67)10018-9CrossrefGoogle Scholar

  • [23] Buege J., Aust S., Microsomal lipid peroxidation, Methods Enzymol., 1978, LII, 302–308 http://dx.doi.org/10.1016/S0076-6879(78)52032-6CrossrefGoogle Scholar

  • [24] Drossos G., Lazou A., Panagopoulos Ph., Westaby S., Deferoxamine Cardioplegia reduces superoxide radical production in human myocardium, Ann. Thorac. Surg., 1995, 59, 169–172 http://dx.doi.org/10.1016/0003-4975(94)00726-NCrossrefGoogle 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 Google Scholar

  • [26] Rotruck J.T., Pope A.L., Ganther H.E., Swanson A.B., Selenium: biochemical role as a component of glutathione peroxidase, Science, 1973, 179, 588–590 http://dx.doi.org/10.1126/science.179.4073.588CrossrefGoogle Scholar

  • [27] Warholm M., Guthenberg C., Bahr C., Mannervik B., Glutathione transferases from human liver, Methods Enzymol., 1985, 113, 499–501 http://dx.doi.org/10.1016/S0076-6879(85)13065-XCrossrefGoogle Scholar

  • [28] Carlberg I., Mannervik B., Glutathione Reductase, Methods Enzymol., 1985, 113, 484–490 http://dx.doi.org/10.1016/S0076-6879(85)13062-4CrossrefGoogle Scholar

  • [29] Putilina F.E., The NADP+-dependent isocitrate dehydrogenase activity determination, Methods Biochem., 1982, 1, 174–176 Google Scholar

  • [30] Anderson M., Determination of glutathione and glutathione disulfide in biological samples, Methods Enzymol., 1985, 113, 548–551 http://dx.doi.org/10.1016/S0076-6879(85)13073-9CrossrefGoogle Scholar

  • [31] Halliwell B., Gutteridge J.M.C., Free radicals in Biology and Medicine, Oxford University Press, Oxford, 1999 Google Scholar

  • [32] Chandel N.S., Budinger S., The cellular basis for diverse responses to oxygen, Free Radic. Biol. Med., 2007, 42, 165–174 http://dx.doi.org/10.1016/j.freeradbiomed.2006.10.048CrossrefGoogle Scholar

  • [33] Yuan G., Adhikary G., McCormick A., Holcroft J., Kumar G., Prabhakar N., Role of oxidative stress in intermittent hypoxia-induced immediate early gene activation in rat PC12 cells, J. Physiol., 2004, 557, 773–783 http://dx.doi.org/10.1113/jphysiol.2003.058503CrossrefGoogle Scholar

  • [34] Faraci F., Didion S., Vascular protection: superoxide dismutase isoforms in the vessel wall, Arterioscler. Thromb. Vasc. Biol., 2004, 24, 1367–1373 http://dx.doi.org/10.1161/01.ATV.0000133604.20182.cfCrossrefGoogle Scholar

  • [35] Jackson R.M., Parish G., Ho Y.S., Effects of hypoxia on expression of superoxide dismutase in cultured ATII cells and lung fibroblasts, Am. J. Physiol. Lung Cell Mol. Physiol., 1996, 271, L955–L962 Google Scholar

  • [36] MacMilan-Crow L.A., Crow J.P., Thompson J.A., Peroxynitrite-mediated inactivation of manganese superoxide dismutase involves nitration and oxidation of critical tyrosine residues, Biochemistry, 1998, 37, 1613–1622 http://dx.doi.org/10.1021/bi971894bCrossrefGoogle Scholar

  • [37] Schild L., Reinheckel T., Reiser M., Horn T., Wolf G., Augustin W., Nitric oxide produced in rat liver mitochondria causes oxidative stress and impairment of respiration after transient hypoxia, FASEB J., 2003, 17, 2194–2201 http://dx.doi.org/10.1096/fj.02-1170comCrossrefGoogle Scholar

  • [38] Lacza Z., Puskar M., Figueroa J., Zhang J., Rajapakse N., Busija D., Mitochondrial nitric oxide synthase is constitutively active and is functionally upregulated in hypoxia, Free Radic. Biol. Med., 2001, 31, 1609–1615 http://dx.doi.org/10.1016/S0891-5849(01)00754-7CrossrefGoogle Scholar

  • [39] Lluis J., Morales A., Blasco C., Colell A., Mari M., Garcia-Ruiz C., et al., Critical role of mitochondrial glutathione in the survival of hepatocytes during hypoxia, J. Biol. Chem., 2005, 280, 3224–3232 http://dx.doi.org/10.1074/jbc.M408244200CrossrefGoogle Scholar

  • [40] Arai M., Imai H., Koumura T., Yoshida M., Emoto K., Umeda M., et al., Mitochondrial phospholipids hydroperoxide glutathione peroxidase plays a major role in preventing oxidative injury to cells, J. Biol. Chem., 1999, 274, 4924–4933 http://dx.doi.org/10.1074/jbc.274.8.4924CrossrefGoogle Scholar

  • [41] Wispe J.R., Clark J.C., Bruhans M.S., Kropp K.E., Korfhagen T.R., Whitsett J.A., Synthesis and processing of the precursor for human manganosuperoxide dismutase, Biochim. Biophys. Acta., 1989, 994, 30–36 Google Scholar

  • [42] Lee S.M., Koh H.J., Park D.C., Song B.J., Huh T.L., Park J.W., Cytosolic NADP+-dependent isocitrate dehyrogenase status modulates oxidative damage to cells, Free Radic.Biol. Med., 2002, 32, 1185–1196 http://dx.doi.org/10.1016/S0891-5849(02)00815-8CrossrefGoogle Scholar

  • [43] Wenger R.H., Cellular adaptation to hypoxia: O2-sensing protein hydroxylases, hypoxia-inducible transcription factors, and O2-regulated gene expression, FASEB J., 2002,16, 1151–1162 http://dx.doi.org/10.1096/fj.01-0944revCrossrefGoogle Scholar

  • [44] Zhai X., Zhou X., Aschraf M., Late ischemic preconditioning is mediated in myocytes by enhanced endogenous antioxidant activity stimulated by oxygen-derived free radicals, Ann. NY Acad. Sci., 1996, 793, 156–166 http://dx.doi.org/10.1111/j.1749-6632.1996.tb33512.xCrossrefGoogle Scholar

About the article

Published Online: 2008-07-12

Published in Print: 2008-09-01

Citation Information: Open Life Sciences, Volume 3, Issue 3, Pages 233–242, ISSN (Online) 2391-5412, DOI: https://doi.org/10.2478/s11535-008-0016-7.

Export Citation

© 2008 Versita Warsaw. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

O. A. Gonchar and I. N. Mankovska
The Ukrainian Biochemical Journal, 2017, Volume 89, Number 6, Page 39
Gustavo Jabor Gozzi, Amanda do Rocio Andrade Pires, Glaucia Regina Martinez, Maria Eliane Merlin Rocha, Guilhermina Rodrigues Noleto, Aurea Echevarria, André Vinicius Canuto, and Sílvia Maria Suter Correia Cadena
Chemico-Biological Interactions, 2013, Volume 205, Number 3, Page 181
Olga Gonchar and Irina Mankovska
Open Life Sciences, 2012, Volume 7, Number 5
O. Gonchar and I. Mankovska
Journal of Biological Sciences, 2010, Volume 10, Number 6, Page 545

Comments (0)

Please log in or register to comment.
Log in