The effects of intermittent hypoxia training on mitochondrial oxygen consumption in rats exposed to skeletal unloading.

Intermittent hypoxia training (IHT) may reduce the oxidative stress-induced damage caused by extreme influences such as ischemia, exhaustive physical exercise, acute hypoxia, and stress. The aim of the present study is to investigate the effects of IHT on hepatic mitochondrial oxygen consumption, lipid peroxidation, and selected biochemical parameters used as diagnostic tools in a skeletal unloading model in rats. Our data showed that the IHT method significantly improved liver tolerance of unloading by reorganizing mitochondrial energy metabolism due to NADH-dependent oxidation. Aminotransferase activity was decreased compared to levels in untreated rats. Succinate dehydrogenase activity and lipid peroxidation remained unchanged when compared between groups. Moreover, skeletal unloading in the growing rats induced an activation of the rate of mitochondrial respiration in state 3 at succinate oxidation and decreased oxygen consumption at α-ketoglutarate oxidation. Adaptation of rats to IHT in our experiment significantly improved the rate of oxidative phosphorylation and the efficiency of phosphorylation in liver mitochondria at α-ketoglutarate oxidation. IHT seems to be a hepatoprotective method, and its use in maintaining a healthy liver and preventing unloading-induced liver damage deserves consideration and further examination.

[1]  Jianhua Zhang,et al.  Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling , 2011, The Biochemical journal.

[2]  Luk'ianova Ld Current issues of adaptation to hypoxia. Signal mechanisms and their role in system regulation , 2011 .

[3]  L. D. Lukianova [Current issues of adaptation to hypoxia. Signal mechanisms and their role in system regulation]. , 2011, Patologicheskaia fiziologiia i eksperimental'naia terapiia.

[4]  J. Sastre,et al.  Targeting mitochondria: a new promising approach for the treatment of liver diseases. , 2010, Current medicinal chemistry.

[5]  Ping Wang,et al.  Effects of simulated weightlessness on liver Hsp70 and Hsp70mRNA expression in rats. , 2009, International journal of clinical and experimental medicine.

[6]  D. Pessayre,et al.  Mitochondrial involvement in drug-induced liver injury. , 2010, Handbook of experimental pharmacology.

[7]  P. Chowdhury,et al.  Oxidant/Anti-Oxidant Status in Rats Exposed to Simulated Weightlessness by Hind-Limb Unloading and Reloading , 2008 .

[8]  E. Germanova,et al.  Effect of intermittent normobaric hypoxia on kinetic properties of mitochondrial enzymes , 2007, Bulletin of Experimental Biology and Medicine.

[9]  J. Sastre,et al.  Mitochondrial function in liver disease. , 2007, Frontiers in bioscience : a journal and virtual library.

[10]  A. P. Sokolov,et al.  Nonezymatic formation of succinate in mitochondria under oxidative stress. , 2006, Free radical biology & medicine.

[11]  R. Freeman,et al.  A shortcut to mitochondrial signaling and pathology: a commentary on "Nonenzymatic formation of succinate in mitochondria under oxidative stress". , 2006, Free radical biology & medicine.

[12]  E. Manukhina,et al.  Role of Nitric Oxide in Cardiovascular Adaptation to Intermittent Hypoxia , 2006, Experimental biology and medicine.

[13]  N. Prabhakar,et al.  Oxidative stress in the systemic and cellular responses to intermittent hypoxia , 2004, Biological chemistry.

[14]  M. N. Kondrashova,et al.  Activation and Inhibition of Succinate-Dependent Ca2+ Transport in Liver Mitochondria during Adaptation , 2001, Biochemistry (Moscow).

[15]  A. Zamotrinsky,et al.  Differences in adaptive stabilization of structures in response to stress and hypoxia relate with the accumulation of hsp70 isoforms , 1992, Molecular and Cellular Biochemistry.

[16]  V. Nosar,et al.  [Effect of intermittent hypoxic training on indices of adaptation to hypoxia in rats during physical exertion]. , 2004, Fiziolohichnyi zhurnal.

[17]  Koliesnikova IeE,et al.  Regulation of oxidative phosphorylation by liver mitochondria receptors after adaptation by rats to periodic normal pressure and acute hypoxia , 2002 .

[18]  T. Serebrovskaya Intermittent hypoxia research in the former soviet union and the commonwealth of independent States: history and review of the concept and selected applications. , 2002, High altitude medicine & biology.

[19]  A. Szewczyk,et al.  Mitochondria as a Pharmacological Target , 2002, Pharmacological Reviews.

[20]  T. V. Serebrovs'ka,et al.  [Regulation of oxidative phosphorylation by liver mitochondria receptors after adaptation by rats to periodic normal pressure and acute hypoxia]. , 2002, Ukrains'kyi biokhimichnyi zhurnal.

[21]  V. Nosar,et al.  [Intermittent hypoxic training with exogenous nitric oxide improves rat liver mitochondrial oxidation and phosphorylation during acute hypoxia]. , 2001, Fiziolohichnyi zhurnal.

[22]  Y. Honda,et al.  Improved 02 Transport and Utilization Capacity Following Intermittent Hypobaric Hypdxia in Rats , 2001 .

[23]  Y. Honda,et al.  Improved O2 transport and utilization capacity following intermittent hypobaric hypoxia in rats. , 2001, Advances in experimental medicine and biology.

[24]  E. Manukhina,et al.  Role of nitric oxide in adaptation to hypoxia and adaptive defense. , 2000, Physiological research.

[25]  V. Skulachev Mitochondrial physiology and pathology; concepts of programmed death of organelles, cells and organisms. , 1999, Molecular aspects of medicine.

[26]  Emily Morey-Holton,et al.  Bone and hormonal changes induced by skeletal unloading in the mature male rat. , 1999, American journal of physiology. Endocrinology and metabolism.

[27]  T. Vanden Hoek,et al.  Mitochondrial electron transport can become a significant source of oxidative injury in cardiomyocytes. , 1997, Journal of molecular and cellular cardiology.

[28]  M. G. Pshennikova,et al.  Adaptive Defense of the Organism , 1996 .

[29]  M. G. Pshennikova,et al.  Adaptive defense of the organism. Architecture of the structural trace and cross protective effects of adaptation. , 1996, Annals of the New York Academy of Sciences.

[30]  F. Muzyka,et al.  [Adrenergic and cholinergic regulation of respiratory efficiency of secretory cells]. , 1994, Fiziolohichnyi zhurnal.

[31]  F. Muzyka,et al.  [EFFect of alpha-ketoglutarate and acetylcholine synergism on energy metabolism in mitochondria]. , 1993, Fiziologicheskii zhurnal.

[32]  Meerson Fz,et al.  Phenomenon of the adaptive stabilization of structures and protection of the heart. , 1992 .

[33]  A. Zamotrinsky,et al.  Phenomenon of the adaptive stabilization of structures and protection of the heart. , 1992, The Canadian journal of cardiology.

[34]  D. Bikle,et al.  Bone response to normal weight bearing after a period of skeletal unloading. , 1989, The American journal of physiology.

[35]  M. N. Kondrashova,et al.  Polarographic observation of substrate‐level phosphorylation and its stimulation by acetylcholine , 1989, FEBS letters.

[36]  E. Morey-Holton,et al.  Skeletal response to simulated weightlessness: a comparison of suspension techniques. , 1987, Aviation, space, and environmental medicine.

[37]  N. Doliba,et al.  [Acetylcholine activation of alpha-ketoglutarate oxidation in liver mitochondria]. , 1986, Ukrainskii biokhimicheskii zhurnal.

[38]  V. I. Kulinskii,et al.  [Activation succinate dehydrogenation in rat liver by noradrenaline, cAMP and acute cooling]. , 1981, Biulleten' eksperimental'noi biologii i meditsiny.

[39]  W. Jee,et al.  Skeletal alterations in rats during space flight. , 1981, Advances in space research : the official journal of the Committee on Space Research.

[40]  M. M. Bradford A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[41]  E. Taft The Mitochondrion: Molecular Basis of Structure and Function , 1964 .

[42]  S REITMAN,et al.  A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. , 1957, American journal of clinical pathology.

[43]  B CHANCE,et al.  The respiratory chain and oxidative phosphorylation. , 1956, Advances in enzymology and related subjects of biochemistry.

[44]  A. Lehninger,et al.  Oxidative phosphorylation. , 1953, Harvey lectures.