Highly sensitive, non-harmful method to detect state of mitochondria in organism by their investigation inside blood lymphocytes in smear Detection of big difference under leucosis and myopathy in young patients compared with healthy ones

The cytobiochemical assay is described in the paper which is elaborated by three of its authors. This method possesses high sensitivity in detection of the state of mitochondria in the organism by measurement of enzyme activity inside blood lymphocytes in smears. Lactate dehydrogenase, succinate dehydrogenase and their ratio LDH/SDH were investigated. The authors proposed to use this ratio as a quantitative indicator of so called Warburg effect, typical of cancer cells. Whereas LDH/SDH is 5.5-8.8 in healthy children, aerobic glycolysis and the indicator rise up to 16.5-55.2 in young patients with leucosis. In children suffering myopathy aerobic glycolysis falls down and the ratio is lower than in norm: 4.5 and less than one. The authors suggested the decrease of aerobic glycolysis under myopathy to be a biomarker of restorative biosynthesis and cell growth weakening inherent in this disease.

cytobiochemistry assay, lymphocyte, respiration, glycolysis, Warburg effect, succinate dehydrogenase, lactate dehydrogenase, leucosis, myopathy

1. Kondrashova M.N., Khunderyakova N.V., Zakharchenko M.V. Original'nyi tsitobiokhimicheskii metod vyyavleniya individual'nykh razlichii fiziologicheskogo sostoyaniya organizma po kompleksnoi kharakteristike (patternu) aktivnosti suktsinatdegidrogenazy. // Rossiiskii Biomeditsinskii Zhurnal. - 2009. - (Biokhimiya). - № 10. - S. 27-43. - www.Medline.ru.

2. Kondrashova M.N., Zakharchenko M.V., Khunderyakova N.V., Fedotcheva N.I., Litvinova E.G., Romanova O.I., Shvartsburd P.M. Innovatsionnye metody diagnostiki v meditsine. Glava 1. Chto daet vrachu opredelenie funktsii mitokhondrii v limfotsitakh bol'nogo. // Monografiya. - 2013. - Novosibirsk. - S. 10-58.

3. Kondrashova M.N., OAO DIOD, Zakharchenko M.V., Khunderyakova N.V., Maevskii E.I. ITEB RAN. Patent Rossiiskoi Federatsii. Tsitobiokhimicheskii sposob opredeleniya aktivnosti suktsinatdegidrogenazy, okisleniya endogennoi yantarnoi kisloty, signal'nogo deistviya mikromolyarnykh kontsentratsii yantarnoi kisloty, ego primenenie dlya kolichestvennoi otsenki urovnya adrenergicheskoi regulyatsii v organizme, sreda i nabor dlya osushchestvleniya sposoba. Prioritet ot 20.11.2007. Opublikovano: 20.08.09. Byulleten' Rospatenta № 23.

4. Kondrashova M.N., Zakharchenko M.V., Khunderyakova N.V. Preservation of the in vivo state of mitochondrial network for ex vivo physioliogicalstudy of mitochondria. // Int. J. Biochem. Cell Biol. - 2009. - № 41. - C. 2036-2050.

5. Zakharchenko M.V., Zakharchenko A.V., Khunderyakova N.V., Tutukina M.N., Simonova M.A., Vasilieva A.A., Romanova O.I., Fedotcheva N.I., Litvinova E.G., Maevsky E.I., Zinchenko V.P, Berezhnov A.V., Morgunov I.G., Gulayev A.A, Kondrashova M.N. Burst of succinate dehydrogenase and a-ketoglutarate dehydrogenase activity in concert with the expression of genes coding for respiratory chain proteins underlies short-term beneficial physiological stress in mitochondria. // Int. J. Biochem. Cell Biol. - 2013. - № 45. - C. 190-200.

6. Kondrashova M.N., Zakharchenko M.V., et al. // Study of Succinate Dehydrogenase and a-Ketoglutarate Dehydrogenase in Mitochondria inside Glass-Adhered Lymphocytes under Physiological Conditions. The Two Dehydrogenases as Counterparts of Adrenaline and Acetylcholine Regulation. in: Dehydrogenases. Ed. by. Canuto R. A. InTech, Italy Turin. - 2012. - S. 235-257.

7. Frelikh G.A., Yanovskaya E.A., Polomeeva N.Yu, Timofeev M.S., Slepichev V.A., Bryushinina O.S., Zyuz’kova Yu.G., Gurto R.V., Vasilev A.S., Semiglazova E.V., Udut V.V. Determination of Mitochondrial Functional State in Vital Tissues by Cytobiochemical Analysis of Peripheral Blood Lymphocytes. // Journal of Endocrine and Metabolic Diseases. - 2013. - № 3. - S. 10-13.

8. Khunderyakova N.V., Zakharchenko M.V., Zakharchenko A.V., Suslikov A.V., Volkov A.V., Telesheva T.Yu., Kondrashova M.N. Priblizhenie k issledovaniyu signal'nogo deistviya yantarnoi kisloty na mitokhondrii v usloviyakh tsitobiokhimicheskogo metoda. // Biologicheskie membrany. - 2012. - Tom 29. - № 6. - S. 442-453.

9. Kondpashova M.N., Zaxapchenko M.V., Khundepyakova N.V., Fedotcheva N.I., Litvinova E.G., Romanova O.I., Gulyaev A.A. Sostoyanie suktsinatdegidrogenazy v organizme - «vyvedennoe iz ravnovesiya» ili giperaktivnoe. // Biofizika. - 2013. - Tom 58. - № 1. - S. 106-116.

10. Khunderyakova N.V., Plyasunova S.A., Litvinova E.G, Yachkula T.V, Zakharchenko M.V., Kovzan A.V., Fedotcheva N.I., Shvartsburd P.M., Kondrashova M.N. Izmeneniya v limfotsitakh pod deistviem substratov okisleniya. // Biofizika. - 2014. - Tom 59. - № 6. - S. 1101-1107.

11. DeBerardinis R., Lum J., Hatzivassilliou G., Thompson G. // Cell Metabolism. - 2008. - № 7. - S. 11.

12. Gogvadze V.L., Orrenius S., Zhivotovsky B. Mitochondria in cancer cells: what is so special about them? // Trends Cell Biol. - 2008. - № 18 (4). - P. 165-73.

13. Matthew G, Heiden V., Cantley L., Thompson G. Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation. // Science. - 2009. - № 324. - S. 1029.

14. Ward P.S., Thompson C.B. Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. // Cancer Cell. - 2012. - № 21. - P. 297-308.

15. Pavlova N. N., Thompson C.B. The Emerging Hallmarks of Cancer Metabolism. // Cell Metab. - 2016. - № 23. - P. 27-47.

16. Schnyder S., Handschin C. Skeletal muscle as an endocrine organ: PGC-1a, myokine s and exercise. // Bone. - 2015. - № 80. - S.115-125.

17. Petruzelli M., Wagner E. Mechanisms of metabolic dysfunction in cancer-associated cachexia. //Genes and development. - 2016. - № 130. - S. 489-501.

18. Corrado Angelini, Nascimbeni A.C., Cenacchi G., Tasca E. Lipolysis and lipophagy in lipid storage myopathies. // Biochimica et Biophysica Acta. - 2016. - № 1862. - S. 1367-1373.

19. Sukhorukov V.S. // Ocherki mitokhondrial'noi patologii. M.: ID «Medpraktika-M». - 2011. - S. 288.