Continuous adaptation of rats to hypobaric hypoxia prevents stressor hyperglycemia and optimizes mitochondrial respiration under acute hypoxia
Portnichenko VI, Nosar VI, Sydorenko AM, Portnichenko AH, Man'kovs'ka IM
- International Centre for Astronomical, Medical and EcologicalResearch NAS of Ukraine, Ukraine
- O.O.Bogomoletz Institute of Physiology NAS of Ukraine, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz58.05.056
Abstract
Oxygen consumption, glucose blood level and liver mi-tochondrial respiration were investigated in male Wistar rats permanently living in middle altitude (2100 m, Elbrus region). The animals were characterized by reduced body oxygen consumption and blood glucose level, as well as by intensifed utilization of NAD-dependent substrates in mitochondrial respiratory chain with increasing indices of ADP-stimulated respiration in comparison with plains rats. As a result of adaptive rebuilding of oxidative metabolism in rats – inhabitants of midlands, the nature and severity of metabolic responses to acute hypoxia were also changed. After lifting in barochamber to a “height’ of 5600 m during 3 hours, plains rats transiently demonstrated hypometabolic and hyperglycemic reactions. A rapid adaptation of mitochondrial function occurred due to increase in the rate of FAD-dependent substrate oxidation accompanied by a decrease in the effectiveness of phosphorylation. In midland rats, by contrast, hypoglycemic reaction was developed, and further reduction of aerobic metabolism was limited. Rapid adaptation of mitochondrial function to acute hypoxia in those rats was more intense than in the plains animals. This was achieved by a signifcant increase in the rate of NAD-dependent substrate oxidation, especially lipids, and an improved effciency of mitochondrial respiration and an increased economy of oxygen utilization.
Keywords:
high altitude hypoxia, acute hypoxia, hyperglycemia,hypoglycemia, hypometabolism, mitochondrial respiration,carbohydrate metabolism, lipid metabolism.
References
- Akmatkulova D.A. Glycemia and glucose tolerance test results in healthy adult residents of the Pamir highlands (2400-4000 m) . Diabetes mellitus in Kyrgyzstan climate . Sb. nauchn. tr. KGMI.. Frunze, 1975. Vol. 105. P.17-23.
- Zapadnyuk IP, Zapadnyuk VI, Zakharia EA, Zapadnyuk BV Laboratory animals. Breeding, keeping, using in experiment. K .: High School, 1983. 384 p.
- Comro J. G., Forster R. E., Dubois A. B., Brisco U. A., Carlsen E. Easy. Clinical Physiology and Functional Trials . Ed. prof. Shika L. M; Medgiz, 1961 196 p.
- Lebkova NP Transformation of lipids into glycogen in animal and human cells . Arch. Pathology. 1982. N 6. p. 68-76.
- Lebkova NP. Ultrastructural organization of mitochondria in hypoxia and its regulation . Hypoxia: destructive and constructive action. 1998. P. 117-118.
- Leninger A. Fundamentals of Biochemistry: In 3 vols Vol.2. M .: Mir, 1985. 368 p.
- Lukyanova LD Modern problems of hypoxia . Vestn. RAMS. 2000. N 9. pp. 3-12.
- Portnichenko VI, Portnichenko AG, Surova OV Hypoglycemia and gene induction in myocardium and rat lungs in hypobaric hypoxia . Achievements of a wedge. and experiment. medicine. 2009. N 2. pp. 65-68.
- Ambrosini G., Nath A.K., Sierra-Honigmann M.R., Flores-Riveros J. Transcriptional activation of the human leptin gene in response to hypoxia. Involvement of hypoxia-inducible factor 1 . J. Biol. Chem. 2002. 277. P.34601-34609.
CrossRef
PubMed
- Chance B., Williams G.R. Respiratory enzymes in oxida-tive phosphorylation. Kinetics of oxygen utilization . Ibid. 1955. 217. P. 383-393.
- Daneshrad Z., Garcia-Riera M.P., Verdys M., Rossi A. Differential responses to chronic hypoxia and dietary restriction of aerobic capacity and enzyme levels in the rat myocardium . Mol. Cell. Biochem. 2000. 210. P.159-166.
CrossRef
PubMed
- Epstein A.C., Gleadle J.M., McNeill L.A., Hewitson K.S., O'Rourke J., Mole D.R., Mukherji M., Metzen E., Wilson M.I., Dhanda A., Tian Y.M., Masson N., Hamilton D.L., Jaakkola P. , Barstead R., Hodgkin J., Maxwell P.H., Pugh C.W., Schofeld C.J., Ratcliffe P.J. C. elegans EGL-9 and mammalian homologs defne a family of dioxygenases that regulate HIF by prolyl hydroxylation . Cell. 2001. 107. P . 43-54.
CrossRef
- Estabrook R.W. Mitochondrial respiratory control and the polarographic measurement of ADP: O Ratios . Metod Enzymol. 1967. 10. P. 41-47.
CrossRef
- Gnaiger E., Renner K. High-Resolution Respirometry with Cultured Cells: A Demonstration Experiment . Mitochon-drial pathways and respiratory control . Ed. E.Chaiger. Innsbruck. OROBOROS MiPNet Publ., 2007. P. 62-68.
- Ke Chen, Yuan-Hai Li, Si-Qi Xu, Sheng-Hong Hu, Lei Zhang. Protective effects of peroxisome proliferator-Activated receptor-a agonist, Wy14643, on hypoxia. reoxygenation injury in primary rat hepatocytes . PPAR Res. 2012. R. 547980.
CrossRef
PubMed PubMedCentral
- Kennedy S.L., StanleyW.C., Panchal A.R., Mazzeo R.S. Alterations in enzymes involved in fat metabolism after acute and chronic altitude exposure . J. Appl. Physiol. 2001. 90. R. 17-22.
CrossRef
PubMed
- Kondrashova M.N., Fedotcheva N.I., Saakyan I.R. Preservation of native properties of mitochondria in rat liver homogenate . Mitochondrion. 2001. N 1. P.249-267.
CrossRef
- Krishnan J., Suter M., Windak R., Krebs T., Felley A., Montessuit C., Tokarska-Schlattner M., Aasum E., Bogdanova A., Perriard E., Perriard J.C., Larsen T., Pedrazzini T., Krek W. Activation of a HIF1alpha-PPARgamma axis underlies the integration of glycolytic and lipid anabolic pathways in pathologic cardiac hypertrophy . Cell Metab. 2009. 9. P. 512-524.
CrossRef
PubMed
- Larsen J.J., Hansen J.M., Olsen N.V., Galbo H., Dela F. The effect of altitude hypoxia on glucose homeostasis in men . J. Physiol. 1997. 504. P.241-249.
CrossRef
PubMed PubMedCentral
- Miranda M., Escote X., Ceperuelo-Mallafre V., Megia A., Caubet E., Naf S., Gomez J. M., Gonzalez-Clemente J. M., Vicente V., Vendrell J. Relation between human LPIN1, hypoxia and endoplasmic reticulum stress genes in subcutaneous and visceral adipose tissue . Int. J. Obes. (London). 2010. 34. P.679-686.
CrossRef
PubMed
- Philp A., Macdonald A.L.,Watt P.W. Lactate a signal coordinating cell and systemic function . J. Exp. Biol. 2006. 208. P. 4561-4575.
CrossRef
PubMed
- Sharma S., Taegtmeyer H., Adrogue J., Razeghi P., Sen S., Ngumbela K., Essop M.F. Dynamic changes of gene expression in hypoxia-induced right ventricular hypertrophy . Amer. J. Physiol. Heart. Circulat. Physiol. 2004. 286. P.1185-1192.
CrossRef
PubMed
- Shen G.M., Zhao Y.Z., Chen M.T., Zhang F.L., Liu X.L., Wang Y., Liu C.Z., Yu J., Zhang J.W. Hypoxia inducible factor 1 (HIF1) promotes LDL and VLDL uptake through inducing VLDLR under hypoxia . Biochem. J. Immed. Public. 2011. October.
CrossRef
PubMed
- Shen G.M., Zhang F.L., Liu X.L., Zhang J.W. Hypoxia-inducible factor 1-mediated regulation of PPP1R3C promotes glycogen accumulation in human MCF-7 cells under hypoxia . FEBS Lett. 2010. 584. P.4366-4372.
CrossRef
PubMed
- Van Liere E.J., Stickney J.C., Hypoxia. Chisago; London: Univ. of Chisago Press. 1963. 367 p.
- Wada Y., Sugiyama A., Yamamoto T., Naito M., Noguchi N., Yokoyama S., Tsujita M., Kawabe Y., Kobayashi M., Izumi A., Kohro T., Tanaka T., Taniguchi H., Koyama H., Hirano K., Yamashita S., Matsuzawa Y., Niki E., Hamak-ubo T., Kodama T. Lipid accumulation in smooth muscle cells under LDL loading is independent of LDL receptor pathway and enhanced by hypoxic conditions . Arterios. Thromb. Vascular Biol. 2002. 22. P.1712-1719.
CrossRef
PubMed
|