Phase changes in energy metabolism during periodic hypoxia
Portnichenko VI, Nosar' VI, Portnichenko AG, Drevitskaia TI, Sidorenko AM, Man'kovskaia IN.
- International Centre for Astronomical, Medical and Ecological Research, NAS of Ukraine, Kyiv, Ukraine
- O.O.Bogomoletz Institute of Physiology, NAS of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz58.04.003
Abstract
Male Wistar rats were exposed to periodic hypobaric hypoxia (PHH), by “lifting” in barochamber at “altitude” 5600 m for 1 h every 3 days (6 s?ances). The dynamics of changes in oxygen consumption (VO2), and body temperature (Tm), as well as in HIF-1a and HIF-3a gene expression, and mitochondrial respiration in the ventricles of the heart was studied. On the basis of the data we identifed four phases of the physiological changes. The frst phase, hypometabolic (1-3 seances), is characterized by decrease in VO2 and Tm, induction of HIF-1a and HIF-3a with delayed transient stimulation of metabolism in response to each seance of hypoxia. In heart mitochondria, V3 and V4 are increased, but V3/V4 and ADP/O are reduced. During the second phase, transitional (3-4 seances), there is reorganization of metabolism and decrease its hypoxic reactivity. The third phase, hypermetabolic (4-5 seances), is characterized by intensifcation of metabolism and compensation of hypoxic disorders. The fourth phase (after 5 seance) – is a state of metabolic adaptation with normalization of VO2 and Tm, expression of HIF-1a and HIF-3a, mitochondrial respiration, increased NAD-dependent oxidation of carbohydrate and lipid substrates. Thus, during PHH consequent rebuilding of processes of oxygen transport, tissue respiration and thermogenesis occurs, mediated by induction of the HIF subunits.
Keywords:
periodic hypoxia, mitochondria, HIF-1a , HIF-3a, hypometabolic state, oxygen consumption.
References
- Lukyanova LD Modern problems of adaptation to hypoxia. Signaling mechanisms and their role in systemic regulation . Patol. physiology and experiment. therapy. 2011. N 1. P.3-19.
- Meerson FZ Adaptation medicine: mechanisms and protective effects of adaptation. M., 1993. 331 p.
- Pozharov VP Automated installation for measuring the volumetric-temporal parameters of external respiration and gas exchange in small laboratory animals . Fiziol. . 1989. 35, No. 4. P.119-121.
- Portnichenko VI, Portnichenko AG, Sidorenko AM Glycemia as a determinant of metabolic pathways and respiration in hypoxia . Pathology. 2011. 8, N 2. pp. 52-55.
- Barros R.C., Zimmer M.E., Branco L.G., Milsom W.K. Hypoxic metabolic response of the golden-mantled ground squirrel . J. Appl. Physiol. 2001. 91, N 2. P. 603-612.
CrossRef
PubMed
- Chance B., Williams G.R. Respiratory enzymes in oxida-tive phosphorylation. Kinetics of oxygen utilization . J. Biol. Chem. 1955. 217. P. 383-393.
- Estabrook R.W. Mitochondrial Respiratory Control and the Polarographic Measurement of ADP: O Ratios . Metod. Enzymol. 1967. 10. P. 41-47.
CrossRef
- Gautier H., Murariu C., Bonora M. Ventilatory and metabolic responses to ambient hypoxia or hypercapnia in rats exposed to CO hypoxia . J. Appl. Physiol. 1997. 83, N 1. P. 253-261.
CrossRef
PubMed
- Hara S., Hamada J., Kobayashi C., Kondo Y, Imura N. Expression and characterization of hypoxia-inducible factor (HIF)-3a in human kidney: suppression of HIF-mediated gene expression by HIF-3a . Biochemet. Biophys. Res. Commun. 2001. 287. P. 808-813.
CrossRef
PubMed
- Heidbreder M., Frohlich F., Johren O., Dendofer A., Qadri F., Dominiak P. Hypoxia rapidly activates HIF-3alpha mRNA expression . FASEB J. 2003. 17, N 11. P.1541-1543.
CrossRef
PubMed
- Intermittent Hypoxia: From Molecular Mechanisms to Clinical Applications (Physiology Laboratory and Clinical Research) . Lei XI (Ed.), Tatiana V. Serebrovskaya (Ed.). Nova Science Pub. Inc., 2010. 615 p.
- Kondrashova M.N., Fedotcheva N.I., Saakyan I.R., Saakyan I.R., Sirota T.V., Lyamzaev K.G., Kulikova M.V., Temnov A.V. Preservation of native properties of mitochondria in rat liver homogenate . Mitochondrion. 2001. 1. P. 249-267.
CrossRef
- Manukhina E.B., Downey H.F., Mallet R.T. Role of Nitric Oxide in Cardiovascular Adaptation to Intermittent Hypoxia . Exp. Biol. Med. (Maywood). 2006. 231, N 4. P. 343-365.
CrossRef
PubMed
- Meerson F.Z. Essentials of Adaptive Medicine: Protective effects of adaptation. Moscow: Hypoxia Medical LTD, 1994.
- Mortola J.P. Implications of hypoxic hypometabolism during mammalian ontogenesis . Respir. Physiol. Neurobiol. 2004. 141, N 3. P. 345-356.
CrossRef
PubMed
- Portnychenko A.G., Dosenko V.E., Portnichenko V.I., Moybenko O.O. Expression of HIF-1a and HIF-3a differentially changed in rat heart ventricles after hypoxic preconditioning . Proc. of XXVIII ESc Meeting of the ISHR. Athens, 2008. Medimond Intern. Proc., 2008. P.61-64.
CrossRef
- Rus A., Del Moral M.L., Molina F., Peinado M.A. Up-regulation of cardiac NO. NOS system during short-term hypoxia and the subsequent reoxygenation period . Eur. J. Histochem. 2011. 55, N 2. P. 91-96.
CrossRef
PubMed PubMedCentral
- Semenza G. Hypoxia-Inducible Factor 1 (HIF-1) Pathway . Sci. STKE. 2007. 407. P. cm8.
CrossRef
PubMed
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