Department of membrane biophysics
Our department is concerned with research of the membrane redox-systems of mitochondria and microsomes, processes of lipid peroxidation, age-dependent cell disfunction and the means of life span increase.
Head of the Department
PhD (Biology), Seniour Researcher Yuriy V. Nikitchenko
Our lab of membrane biophysics at Kharkov university was founded in 1980 by professor Victor Lemeshko. For over 25 years the investigation of membrane redox-systems of mitochondria and microsomes, and processes of lipid peroxidation has been carried out in our laboratory. The main attention is given to the clarification of age-related changes mechanism in the activity and regulation of these systems. Recently, efforts have been directed toward investigation of various aspects of molecular mechanism of ageing, age-dependent cell disfunction, senescence accelerated by various factors and the means of improvement of”quality of life” and life span increase.
Research interests focus mainly on age-related alterations of membrane redox-systems, general mechanisms of ageing, and the means of life span increase.
Nikitchenko, Yuri V., Ph.D.(Biology)
Mechanisms of age-related alterations of lipid peroxidation, means of life span increase.
Padalko, Vladimir I., Ph.D.(Biology)
Mechanisms of age-related alterations of xenobiotics metabolism, means of life span increase.
Dzuba, Victoria N., Ph.D.(Biology)
Mitochondrial oxidative phosphorylation system.
Leonova, Iryna S., Ph.D. (Biology)
Means of life span increase, calorie restricted diet.
In the result of a detailed study of mitochondrial oxidative phosphorylation, there were determined peculiarities of changes with age in activities of ATP-synthase, NAD- and FAD-dependent dehydrogenases and cytochromes content. It was proposed the proton-chemical hypothesis of energy coupling (Lemeshko, 1980-1982) allowing to explain a number of facts contradicting to the chemiosmotic coupling principle. This assumption is supported by the theoretical analysis of the mathematical model of energy coupling system.
Our group has been investigating permeability transition of the mitochondrial inner membrane, leading to the release of apoptosis inducing cytochrome c from intermembrane space. Special attention is devoted to the following aspects of this problem: role of lipid peroxidation, pro- and antioxidants, effect of calcium and phosphate contents, osmotic pressure effect, age-related changes in the mitochondria permeability transition process, role of ischemic tissue injury, effect of mitochondria cryodamage and reparation after freezing and thawing, effect of thyroid hormones. One of the new directions of the research is study of hidh-amplitude swelling of mitochondria and rotenone-insensitive NADH oxidation.
Another direction in our department is the investigation of the role of microsomal metabolism of xenobiotics in the mechanism of natural, slowed and accelerated aging of organism. Structural and functional changes of microsomal membranes have been shown to play the leading role in the characters of xenobiotics action at the different stages of organism development. In particular, age-related differences in xenobiotics action on liver microsomes were shown to be likely related to the decrease of their metabolism rate.
The study of free radical lipid peroxidation is one of the main investigation directions in our department. We study intensity of lipid peroxidation and its regulation under natural aging and at the models of slowed and accelerated aging. The obtained results allow to interpret more correctly free radical theory of aging.
We have worked up several criteria for new geroprotectors search. Lipid hydroperoxide content and Se-dependent glutathione peroxidase activity changes have been shown as the most informative ones. The search of effective methods and means of longevity increase is also conducted in our department. Special attention is devoted to natural antioxidants. To reveal the most effective ones more than 300 plant extracts were studied. These data may become a basis for the creation of new pharmacological preparations with gero-, cardio-, and hepatoprotective action.
Analysis of obtained data and results of previously fulfilled investigations allowed to make the conclusion that the optimum strategy for the correction of age-dependent changes of antioxidant system with the purpose of life-span increase and delay of appearence and development of age-dependent pathologies should consist in the following: a) increase of enzymatic antioxidant system activity and especially significant increase of GSH-dependent antioxidant enzymes activities; b) increase of glutathione reductase activity to the level of young organism; c) increase of the contribution of isocitrate dehydrogenase activity in the generation of reduced NADPH in cell; d) increase of activity of non-enzymatic antioxidant system of membranes and soluble cell fraction. Such correction of age-dependent changes of antioxidant system will be accompanied by the decrease of the rate of reactive oxygen species generation in mitochondria, the decrease of intensity of induced lipid peroxidation in membranes and accumulation of TBA-reactive products of lipid peroxidation in tissues and by the increase of mitochondrial membrane stability.
At present the most intensive investigations are carried out in the following directions:
The study of enzymatic regulation of free radical lipid peroxidation under action of factors modulating the aging rate (in particular, calorie-restricted diet);
The study of the role of changes in microsomal structure and functional state in the accelerated aging process caused by the influence of environmental chemicals;
The study of mitochondrial structure and functional state under slowed and accelerated aging;
The study of the officina1 plants extracts as potential membrane- and geroprotectors;
Developing the mathematical model of mitochondrial inner membrane permeability transition.
List of Selected Publications:
1. Sukhodub A.L.,Padalko V.I. Age-dependent changes in rat liver microsomal membrane structure and function under benzene treatment// Mech. Ageing and Dev. – 1999. – V. 106, N3. – P. 273 – 282.
Nikitchenko Yu.V.,Romanko M.E.,Dzuba V.N.,Fooks P.P. Lipid peroxidation and its regulation in the rats blood and liver under the experimental alimentary radionuclide effect // Ukr. biochim.j. -2001.-75, N5.-P.43-48.
3. Bilostotska L.I., Nikitchenko Yu.V., Dzyuba V.N. The effect of 2-month calorie-restricted diet on mitochondrial functional state and mass of rats liver, heart and brain // Biogerontology. – 2002. – V. 3, Suppl. 1. – P. 29 – 30. (in Russian)
4. Padalko V.I., Kozlova E.V. Isoform-specific damage of cytochrome P-450 by hepatotoxins in rats of different age // Biogerontology. – 2002. – V. 3, Suppl. 1. – P. 85.
5. V. I. Padalko Influence of calorie restricted diet on the liver microsomal monooxygenase system in different age rats // Ukr.biochim.j., 2003, V. 75, N 4, p. 108-114.(in Russian)
6. I.S. Leonova, A.I. Bozhkov / Induction of Sterol Biosynthesis in Saccharomyces cerevisiae by Enzyme Complex of Chaetomium globossum // Act. Problemy Biologiji i Mediciny (Kiev). – 2004. – N 1. – P. 303-308. (in Russian)
7. A.I. Bozhkov, I.S. Leonova, and V.I. Oblak / Elimination of Saccharomyces cerevisiae Cell Wall using the Enzyme Complex of Chaetomium globossum Kunze // Biotechnologija (Moscow). – 2004. – N 6. – P. 46-54. (in Russian)
8. Tkachenko V.Ì., Nikitchenko Yu.V., Tovstiak V.V. The effect of gamma-radiation and alimentary factors on the content and activity of membrane-bound enzymes of detoxication in rat liver microsomes // Biologiya tvarin. – 2004. – V. 6, N1, 2. – P. 196 – 202. (in Ukrainian)
9. Yu.V. Nikitchenko, V.M. Dzyuba, G.O. Zolotukhina, V.V. Bondar. The state of prooxidant-antioxidant balance in liver and blood of young and old rats under sodium nitroprusside injection // Bukovinskiy Medichniy Visnik. – 2005. – N2. – P. 173 – 174. (in Ukrainian)
10. L.I. Belostotskaya, O.N. Gomon, Yu.V. Nikitchenko, L.A. Chaika, V.V. Bondar, V.N. Dzyuba. Prooxidant-antioxidant balance in prostata and blood of rats under sulpyride-induced prostate hyperplasia and correction by prostatilen // Bul. Exp. Biology and Medicine (Moscow). – 2005. – V. 139, N 3. – P. 313 – 315. (in Russian)
11. Padalko V. Uncoupler of Oxidative Phosphorylation Prolongs the Lifespan of Drosophila // Biochemistry (Moscow) 2005, Vol. 70, No. 9, 986-989.
12. Bilostotska L.I., Nikitchenko Yu.V., Gomon O.N., Chaika L.A., Bondar V.V., Dzyuba V.N. The effect of biologically active substances of animal and plant origin on prooxidant-antioxidant balance under experimental hyperplasia of prostate in rats // Experim. Clin. Pharmacol. – 2006. – V. 169, N 4. – Ñ. 66 – 68 (in Russian).
13. Volyanskiy A.Yu., Simirenko L.L., Paliy I.G., Kuchma I.Yu., Nikitchenko Yu.V. Age-specific thyroid status characteristics of rats during immunization with ADT-anatoxin // Biomedical and Biosocial Anthropology. – 2006. – N. 7. – P. 159 – 164 (in Ukrainian).
14. Petrenko A., Ochenashko O., Nikitchenko Yu., Fuller B. Hepatic recovery in rats with CCl4-induced cirrhosis after transplantation of allogeneic and xenogeneic cryopreserved liver cells from fetal or adult origin // 8th Int. Congr. of the Cell Transplant Society (Milano, Italy – May 18 – 20, 2006). – P. 55.
15. Gorbenko V.N., Ovsiannikova T.N., Nikitchenko Yu.V., Tishko T.V. The contribution of membrane modification to thyroid cancer pathogenesis // International Medical Journal. – 2007. – V. 13, N 2. – P. 101 – 104 (in Russian).
16. Ochenashko O.V., Nikitchenko Y.V., Volkova N.A., Mazur S.P., Somov A.Y., Fuller B.J., Petrenko A.Y. Functional hepatic recovery after xenotransplantation of cryopreserved fetal liver cells or soluble cell-factor administration in a cirrhotic rat model: Are viable cells necessary? // J. Gastroenterol. and Hepatol. – 2007, doi 10.1111/j.1440-1746.2007.05095.x.
17. Bilostotska L.I., Padalko V.I., Nikitchenko Yu.V. Age peculiarities of calorie restriction effect on respiration and oxidative phosphorylation of rat liver mitochondria // Abstract Book of VI Eur. Congr. “Healthy and active ageing for all europeans (July 5 – 8, 2007, Saint Petrsburg, Russia). – Adv. Gerontol. – 2007. – V. 20, N 3. – P. 21 – 22.
18. Vladimir I. Padalko, Anatoliy I. Bozhkov, Yuriy V. Nikitchenko Hepatic monooxygenase system, lipid peroxidation and antioxidant defense system in lead-poisoned rats of different age // Molecular Mechanism of Diseases, Souvenir and Abstracts International Conference,December 15-16, 2008, Gwalior, India, GL-18
19. Bilostotska L.I., Dzyuba V.N., Nikitchenko Yu.V. The effect of three different hypocaloric diets on oxidative phosphorylation and activity of enzymatic antioxidant system in rat liver mitochondria // Adv. Gerontol. – 2008. – Vol. 21, N 2. – P. 235 – 239. (In Russian)
20. Nikitchenko Yu.V., Padalko V.I., Tkachenko V.N., Zolotukhina A.A., Tovstiak V.V. The influence of g-irradiation and alimentary factors on prooxidant-antioxidant rat’s liver and blood system // Radiatsionnaya Biologiya. Radioekologiya. – 2008. – Vol. 48, N 2. – P. 171 – 176. (In Russian)
21. Nikitchenko Yu.V., Padalko V.I., Tkachenko V.M., Sheremet Y.O., Tovstiak V.V. The activity of glutathione-dependent antioxidant system in rat’s liver and blood depending on g-irradiation and nutrition // Ukr. Biochim. J. – 2008. – Vol. 80, N 6. – P. 66 – 73. (In Ukrainian)
22. Ochenashko O.V., Nikitchenko Yu.V., Sheremet A.A., Petrenko A.Yu. Effect of fetal liver cryopreserved cells on survival, state of prooxidant-antioxidant and monooxigenase systems of rats during ageing // Problems of Cryobiology. – 2008. – Vol. 18, N 4. – P. 453 – 455. (In Russian)
23. Nikitchenko Yu.V. The role of alimentary factors in age-dependent changes of organism prooxidant-antioxidant system // Problemi Stareniya I Dolgoletiya. – 2009. – Vol. 18, N 1. – P. 72 – 77. (In Russian)
24. Padalko V.I., Leonova I.S., Kozlova E.V. The effect of calorie restricted diet on life span and some indices of biological age of Drosophila melanogaster // Problemi Stareniya I Dolgoletiya. – 2009. – Vol. 18, N 1. – P. 64 – 71. (In Russian)
V. I. Padalko, I. S. Leonova, E. V. Kozlova The effect of 2,4-dinitrophenil on the intensity of oxidative processes in rat liver during longitudinal experiment // Adv. gerontol. – 2010. -Vol. 23, ¹ 1. – P. 98–103 . (In Russian)
Bozhkov A., Padalko V., Dlubovskaya V., Menzianova N. Resistance to heavy metals toxicity in organisms under chronic exposure // Indian J. of Exp. Biology, 2010, 48, P. 679-696.
27. Anshu Jain, Abhishek Yadav, A.I. Bozhkov, V.I. Padalko and S.J.S. Flora. Therapeutic efficacy of silymarin and naringenin in reducing arsenic-induced hepatic damage in young rats. // Ecotoxicol. Environ. Saf., 2011, 74,P. 607-614.
We are open for scientific cooperation, welcome establishing scientific contacts and look for financial support of our research.