Ukr.Biochem.J. 2014; Volume 86, Issue 6, Nov-Dec, pp. 106-118

doi: https://doi.org/10.15407/ubj86.06.106

Functional and dynamic state of inner mitochondrial membrane of sarcoma 37 in mice under administration of sodium dichloroacetate

S. V. Khyzhnyak1, L. V. Sorokina2, L. I. Stepanova3, A. A. Kaplia4

1National University of Life and Environmental Sciences of Ukraine, Kyiv;
e-mail: khs2014@ukr.net;
2R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology,
National Academy of Sciences of Ukraine, Kyiv;
3ESC “Institute of Biology”, Taras Shevchenko National University of Kyiv, Ukraine;
4Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv

The activity of enzymes of the respiratory chain and structural-dynamic properties of the inner mitochondrial membrane (IMM) of sarcoma 37 (S37) in mice under  sodium dichloroacetate (SDA) administration in a daily dose of 86 mg/kg of body weight starting from the 2nd day after tumor transplantation were investigated. The dynamic and structural state of the IMM components was determined using the fluorescent probes. With S37 growth the intensification of glycolytic metabolism occurred on the background of suppressed functional capacity of mitochondrial respiratory chain enzymes. The changes of conformational properties of protein molecules and the increase of IMM lipid phase microviscosity were shown. The administration of SDA promotes the decrease of lactate content and the increase of pyruvate dehydrogenase activity in S37. This was accompanied by further suppression of the functional activity of the respiratory chain complexes and Н+-АТРase coupled with conformational modification of protein molecules and changes of the structural orderliness of the IMM lipid phase, possibly due to intensification of reactive oxygen species generation.

Keywords: , , , , , ,


References:

  1. Brahimi-Horn MC, Bellot G, Pouysségur J. Hypoxia and energetic tumour metabolism. Curr Opin Genet Dev. 2011 Feb;21(1):67-72. Review. PubMed, CrossRef
  2. Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol. 2003 Oct 15;552(Pt 2):335-44. Review. PubMed, PubMedCentral, CrossRef
  3. Fogg VC, Lanning NJ, Mackeigan JP. Mitochondria in cancer: at the crossroads of life and death. Chin J Cancer. 2011 Aug;30(8):526-39. Review. PubMed, PubMedCentral, CrossRef
  4. Michelakis ED, Webster L, Mackey JR. Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer. Br J Cancer. 2008 Oct 7;99(7):989-94. Review. PubMed, PubMedCentral, CrossRef
  5. Wong JY, Huggins GS, Debidda M, Munshi NC, De Vivo I. Dichloroacetate induces apoptosis in endometrial cancer cells. Gynecol Oncol. 2008 Jun;109(3):394-402.  PubMed, PubMedCentral, CrossRef
  6. Archer SL, Gomberg-Maitland M, Maitland ML, Rich S, Garcia JG, Weir EK. Mitochondrial metabolism, redox signaling, and fusion: a mitochondria-ROS-HIF-1alpha-Kv1.5 O2-sensing pathway at the intersection of pulmonary hypertension and cancer. Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H570-8. Review. PubMed, CrossRef
  7. McMurtry MS, Bonnet S, Wu X, Dyck JR, Haromy A, Hashimoto K, Michelakis ED. Dichloroacetate prevents and reverses pulmonary hypertension by inducing pulmonary artery smooth muscle cell apoptosis. Circ Res. 2004 Oct 15;95(8):830-40. PubMed, CrossRef
  8. Kimura S, Ohtuki N, Nezu A, Tanaka M, Takeshita S. Clinical and radiologic improvements in mitochondrial encephalomyelopathy following sodium dichloroacetate therapy. Brain Dev. 1997 Dec;19(8):535-40. PubMed, CrossRef
  9. Diller IC. Cytological studies of sarcoma 37. Growth. 1952 Jun;16(2):109-25. PubMed
  10. Workshop on biochemistry: a training manual.Ed. by S. E.Severin, G. A. Soloviova. M.: Moscow State University publishing house, 1989. 509 p. (In Russian).
  11. Sun RC, Fadia M, Dahlstrom JE, Parish CR, Board PG, Blackburn AC. Reversal of the glycolytic phenotype by dichloroacetate inhibits metastatic breast cancer cell growth in vitro and in vivo. Breast Cancer Res Treat. 2010 Feb;120(1):253-60. PubMed, CrossRef
  12. Padh H. Proceedings of the 13th Workshop of the Association for Biology Laboratory Education (ABLE). 1992;13:129-146.
  13. Sorokina LV, Solyanik GI, Pyatchanina TV. The evaluation of prooxidant and antioxidant state of two variants of lewis lung carcinoma: a comparative study. Exp Oncol. 2010 Dec;32(4):249-53. PubMed
  14. Tfelt-Hansen P, Siggaard-Andersen O. Lactate and pyruvate determination in 50 mu-1 whole blood. Scand J Clin Lab Invest. 1971 Feb;27(1):15-9. PubMed, CrossRef
  15. Hinman LM, Blass JP. An NADH-linked spectrophotometric assay for pyruvate dehydrogenase complex in crude tissue homogenates. J Biol Chem. 1981 Jul 10;256(13):6583-6. PubMed
  16. Hardy L, Clark JB, Darley-Usmar VM, Smith DR, Stone D. Reoxygenation-dependent decrease in mitochondrial NADH:CoQ reductase (Complex I) activity in the hypoxic/reoxygenated rat heart. Biochem J. 1991 Feb 15;274(Pt 1):133-7. PubMed, PubMedCentral, CrossRef
  17. Cardoso SM, Proença MT, Santos S, Santana I, Oliveira CR. Cytochrome c oxidase is decreased in Alzheimer’s disease platelets. Neurobiol Aging. 2004 Jan;25(1):105-10. PubMed, CrossRef
  18. Krause F, Reifschneider NH, Goto S, Dencher NA. Active oligomeric ATP synthases in mammalian mitochondria. Biochem Biophys Res Commun. 2005 Apr 8;329(2):583-90. PubMed, CrossRef
  19. Zhirnov VV, Khyzhnyak SV, Voitsitskiy VM. The effects of ultra-low dose beta-radiation on the physical properties of human erythrocyte membranes. Int J Radiat Biol. 2010 Jun;86(6):499-506. PubMed, CrossRef
  20. Sorokina LV, Pyatchanina TV, Didenko GV, Kaplia AA, Khyzhnyak SV. The influence of sodium dichloroacetate on the oxidative processes in sarcoma 37. Exp Oncol. 2011 Dec;33(4):216-21. PubMed
  21. Stacpoole PW, Nagaraja NV, Hutson AD. Efficacy of dichloroacetate as a lactate-lowering drug. J Clin Pharmacol. 2003 Jul;43(7):683-91. Review. PubMed, CrossRef
  22. Gogvadze VG, Bruetovetskiy NN, Zhukova AA. Participation of phospholipase A2 in uncoupling in rat liver mitochondria induced by products of lipid peroxidation. Biokhimiia (Moscow). 1990 Dec;55(12):2195-9. Russian. PubMed
  23. Stacpoole PW, Henderson GN, Yan Z, James MO. Clinical pharmacology and toxicology of dichloroacetate. Environ Health Perspect. 1998 Aug;106(Suppl 4):989-94. PubMed, PubMedCentral, CrossRef
  24. Kennedy KM, Dewhirst MW. Tumor metabolism of lactate: the influence and therapeutic potential for MCT and CD147 regulation. Future Oncol. 2010 Jan;6(1):127-48. Review. PubMed, PubMedCentral, CrossRef
  25. Chen Z, Lu W, Garcia-Prieto C, Huang P. The Warburg effect and its cancer therapeutic implications. J Bioenerg Biomembr. 2007 Jun;39(3):267-74. Review. PubMed, CrossRef
  26. Heerdt BG, Houston MA, Augenlicht LH. The intrinsic mitochondrial membrane potential of colonic carcinoma cells is linked to the probability of tumor progression. Cancer Res. 2005 Nov 1;65(21):9861-7. PubMed, CrossRef
  27. Briere JJ, Benit P, Rustin P. The electron transport chain and carcinogenesis. In: Cellular Respiration and Carcinogenesis. Ed. by S.P. Apte, R. Sarangarajan. N.Y.: Humana Press, 2009. P. 19-32. CrossRef
  28. Baysal BE, Ferrell RE, Willett-Brozick JE, Lawrence EC, Myssiorek D, Bosch A, van der Mey A, Taschner PE, Rubinstein WS, Myers EN, Richard CW 3rd, Cornelisse CJ, Devilee P, Devlin B. Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science. 2000 Feb 4;287(5454):848-51. PubMed, CrossRef
  29. Simonnet H, Alazard N, Pfeiffer K, Gallou C, Béroud C, Demont J, Bouvier R, Schägger H, Godinot C. Low mitochondrial respiratory chain content correlates with tumor aggressiveness in renal cell carcinoma. Carcinogenesis. 2002 May;23(5):759-68. PubMed, CrossRef
  30. Sun AS, Sepkowitz K, Geller SA. A study of some mitochondrial and peroxisomal enzymes in human colonic adenocarcinoma. Lab Invest. 1981 Jan;44(1):13-7. PubMed
  31. Fukuda R, Zhang H, Kim JW, Shimoda L, Dang CV, Semenza GL. HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. Cell. 2007 Apr 6;129(1):111-22. PubMed, CrossRef
  32. Muller FL, Roberts AG, Bowman MK, Kramer DM. Architecture of the Qo site of the cytochrome bc1 complex probed by superoxide production. Biochemistry. 2003 Jun 3;42(21):6493-9. PubMed, CrossRef
  33. Sorokina LV, Маkоvеtskа LI, Didenko GV, Ganzha ОB, Khyzhnyak SV. The modi­fication of prooxidant and antioxidant state of sarcoma 37 cells under using of sodium dichloroacetate. Scientific conference “Biologically active substances: fundamental and applied problems” (Novy Svet, Crimea, May 2011). Р. 606.
  34. Chen JJ, Yu BP. Alterations in mitochondrial membrane fluidity by lipid peroxidation products. Free Radic Biol Med. 1994 Nov;17(5):411-8. PubMed, CrossRef
  35. Andreyev AY, Kushnareva YE, Starkov AA. Mitochondrial metabolism of reactive oxygen species. Biochemistry (Mosc). 2005 Feb;70(2):200-14. Review. PubMed, CrossRef

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.