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Protein 70 kDa in the control of sleep and thermoregulation

  • Comparative and Ontogenic Physiology
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Abstract

Studies of expression of molecular chaperones of the family of Heat Shock Proteins 70 kDa (HSP70) in the mouse and rat brain during sleep deprivation do not answer the question whether the HSP70 produce somnogenic effect. In the present work there are studied effects of exogenous Hsp70 that is known to be able to penetrate into living cells in vitro and to acquire properties of endogenous chaperone. Hsp70 was microinjected into the third brain ventricle of rats and pigeons at the beginning of the non-active 24-h phase when under natural conditions the sleep duration increases and the somato-visceral parameters decrease. Hsp70 has been established to enhance this natural process and to produce an additional increase of the total time of slow-wave sleep, a more pronounced inhibition of the muscle contractive activity, and a deeper decrease of the brain temperature. A similarity in effects of Hsp70 in rats and pigeons has been revealed. In both species the somnogenic Hsp70 action is realized by activation of mechanisms of maintenance of the longer episodes of the slow-wave sleep. The hypothermic Hsp70 effect seems to be associated with a decrease of the muscle contractive activity level, rather than with an enhancement of peripheral vasodilation and with an increase of heat loss. A hypothesis is put forward that the hyposedative/neuroleptic-like Hsp70 action that includes the somnogenic, myorelaxing, and hypothermic effects is mediated by activation of GABAA receptors of the main inhibitory brain system.

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References

  1. Rechtschaffen, A., Current Perspectives on the Function of Sleep, Persp. Biol. Med., 1998, vol. 43, pp. 359–390.

    Google Scholar 

  2. Kovalzon, V.M., Pastukhov, Yu.F., and Mukhametov, L.M., Mechanisms of Sleep, Fiziologiya cheloveka i zhivotnykh (Human and Animal Physiology), vol. 31, Moscow: VINITI, 1986.

    Google Scholar 

  3. Obal, F. and Krueger, J.M., Biochemical Regulation of Non-Rapid-Eye-Movement Sleep, Front. Biosci., 2003, pp. 520–550.

  4. Saper, C.B., Scammel, T.E., and Lu, J., Hypothalamic Regulation of Sleep and Circadian Rhythms, Nature, 2005, vol. 437, pp. 1257–1263.

    Article  CAS  PubMed  Google Scholar 

  5. Ekimova, I.V. and Pastukhov, Yu.F., Participation of GABAergic Mechanisms of Hypothalamus Ventrolateral Preoptic Area in Regulation of Sleep and Wakefulness States and of Temperature Homeostasis in the Pigeon Colimbia livia, Zh. Evol. Biokhim. Fiziol., 2005, vol. 41, pp. 356–363.

    CAS  PubMed  Google Scholar 

  6. Cirelli, C. and Tononi, G., Gene Expression in the Brain across the Sleep-Waking Cycle, Brain Res., 2000, vol. 885, pp. 303–321.

    Article  CAS  PubMed  Google Scholar 

  7. Terao, A., Greco, M.A., Davis, R.W., Heller, H.C., and Kilduff, T.S., Region-Specific Changes in Immediate Early Gene Expression in Response to Sleep Deprivation and Recovery Sleep in the Mouse Brain, Neurosci., 2003, vol. 4, no. 120, pp. 1115–1124.

    Article  Google Scholar 

  8. Ellis, R.J., The Molecular Chaperone Concept, Semin. Cell Biol., 1990, vol. 1, pp. 1–9.

    CAS  PubMed  Google Scholar 

  9. Kiang, J.G. and Tsokos, G.C., Heat Shock Protein 70kDa: Molecular Biology, Biochemistry, and Physiology, Pharmacol. Ther., 1998, vol. 80, pp. 183–201.

    Article  CAS  PubMed  Google Scholar 

  10. Margulis, B.A. and Guzhova, I.V., Stress Proteins in Eukaryotic Cell, Tsitologiya, 2002, vol. 42, pp. 323–342.

    Google Scholar 

  11. Pastukhov, Yu.F. and Ekimova, I.V., Molecular, Cellular, and Systemic Mechanisms of Protective Function of the Heat Shock Protein 70 kDa, Neironauki, 2005, vol. 2, no. 2, pp. 3–25.

    Google Scholar 

  12. Shaw, P.J., Tononi, G., Greenspan, R.J., and Robinson, D.F., Stress Response Genes Protect against Lethal Effects of Sleep Deprivation in Drosophila, Nature, 2002, vol. 417, pp. 287–291.

    Article  CAS  PubMed  Google Scholar 

  13. Naidoo, N., Giang, W., Galante, R.J., and Pack, A.I., Sleep Deprivation Induces the Unfolded Protein Response in Mouse Cerebral Cortex, J. Neurochem., 2005, vol. 92, pp. 1150–1157.

    Article  CAS  PubMed  Google Scholar 

  14. Terao, A., Steininger, T.L., Hyder, K., Apte-Deshpande, A., Ding, J., Rishipathak, D., Davis, R.W., Heller, H.C., and Kilduff, T.S., Differential Increase in the Expression of Heat Shock Protein Family Members during Sleep Deprivation and during Sleep, Neurosci., 2004, vol. 116, pp. 187–200.

    Article  Google Scholar 

  15. Cirelli, C., Gutierrez, C.M., and Tononi, G., Extensive and Divergent Effects of Sleep and Wakefulness on Brain Gene Expression, Neuron, 2004, vol. 41, pp. 35–43.

    Article  CAS  PubMed  Google Scholar 

  16. Sazonov, V.S. and Pastukhov, Yu.F., Intracircadian Organization of the Wakefulness-Sleep Cycle and Energy Metabolism in Rats at Action of the Low Environmental Temperature, Fiziol. Zh. SSSR, 1985, vol. 71, pp. 342–346.

    CAS  PubMed  Google Scholar 

  17. Alfoldi, P., Rubicsek, G., Cserni, G., and Obal, F., Jr., Brain and Core Temperatures and Peripheral Vasomotion during Sleep and Wakefulness at Various Ambient Temperatures in the Rat, Pflbgers Arch., 1990, vol. 417, pp. 336–341.

    Article  CAS  Google Scholar 

  18. Rashotte, M.E., Pastukhov, Iu.F., Poliakov, E.L., and Henderson, R.P., Vilgilance States and Body Temperature during Circadian Cycle in Fed Fasted Pigeons, Am. J. Physiol. Regulat. Integrat. Comp. Physiol., 1998, vol. 275, pp. R1690–R1702.

    CAS  Google Scholar 

  19. Pastukhov, Yu.F., Ekimova, I.V., Nozdrachev, A.D., Guselnikova, E.A., Sedunova, E.V., and Zimin, A.L., The Sleep State Makes a Significant Contribution both to “Cooling” and to “Warming” of Brain at the Dark Circadian Phase in Pigeons, Dokl. RAN, 2001, vol. 375, pp. 836–840.

    Google Scholar 

  20. Heller, H.C., Temperature, Thermoregulation and Sleep, Principles and Practice of Sleep Medicine, vol. 4, Kryger, M.K., Roth, T., and Dement, W.C., Eds., Philadelphia: Elsevier Saunders, 2005, pp. 292–304.

    Chapter  Google Scholar 

  21. Kimg, Y.T., Lin, C.S., Lin, J.H., and Lee, W.C., Whole-Body Hyperthermia-Induced Thermotolerance Is Associated with the Induction of Heat Shock Protein 70 in Mice, J. Exp. Biol., 2002n, vol. 205, pp. 273–278.

    Google Scholar 

  22. Pastukhov, Yu.F., Ekimova, I.V., and Guzhova, I.V., The Main Stress Protein Has Pyrogenic Action, Dokl. RAN, 2003, vol. 388, pp. 837–841.

    Google Scholar 

  23. Pastukhov, Yu.F., Ekimova, I.V., Guzhova, I.V., and Khudik, K.A., Integrative Mechanisms of Realization of Pyrogenic and Somnogenic Effects of Heat Shock Protein 70 kDa: a Hypothesis, Problemy integratsii funktsii v fiziologii i meditsine (Problems of Integration of Functions in Physiology and Medicine), Minsk, 2004, pp. 291–298.

  24. Pastukhov, Yu.F., Ekimova, I.V., Khudik, K.A., and Guzhova, I.V., Heat Shock Protein 70 kDa Free of Lipopolysaccharide Has Hypothermic and Somnogenic Action, Dokl. RAN, 2005, vol. 402, pp. 275–278.

    Google Scholar 

  25. Paxinos, G. and Watson, C., The Rat Brain in Stereotaxic Coordinates, San Diego, Avad., 1998.

    Google Scholar 

  26. Karten, H.J. and Hodos, W., A Stereotaxic Atlas of the Brain of the Pigeon (Columbia livia), Baltimore, Maryland: Hohns Hopkins, 1967.

    Google Scholar 

  27. Ekimova, I.V., Thermoregulation in Pigeon Columbia livia during Stress Produced by Food Deprivation, Zh. Evol. Biokhim. Fiziol., 2005, vol. 41, pp. 62–68.

    Google Scholar 

  28. Evdonin, A.L., Martynova, M.G., Bystrova, O.A., Guzhova, I.V., Margulis, B.A., Medvedeva, N.D., The Release of Hsp70 from A431 Carcinoma Is Mediated by Secretory-Like Granules, Eur. J. Cell Biol., 2006, vol. 85, pp. 443–455.

    Article  CAS  PubMed  Google Scholar 

  29. Guzhova, I.V., Kislyakova, K., Moskaliova, O., Fridlanskaya, M., Tytell, M., Cheetham, B., and Margulis, B.A., In vitro Studies Show That Hsp70 Can Be Released by Glia That Exogenous Hsp70 Can Enhance Neuronal Stress Tolerance, Brain Res., 2001, vol. 914, pp. 66–73.

    Article  CAS  PubMed  Google Scholar 

  30. Guzhova, I.V. and Margulis, B.A., Induction and Accumulation of BTSh70 Leads to Formation of Its Complexes with Other Cellular Complexes, Tsitologiya, 2000, vol. 42, pp. 647–652.

    CAS  Google Scholar 

  31. Lu, J., Greco, M.A., Shiromani, P., and Saper, C.B., Effect of Lesions of the Ventrolateral Preoptic Nucleus on NREM and REM Sleep, J. Neurosci., 2000, vol. 20, pp. 3830–3842.

    CAS  PubMed  Google Scholar 

  32. Sherin, J.E., Shiromani, P.J., McCarley, R.W., and Saper, C.B., Activation of Ventrolateral Preoptic Neurons during Sleep, Science, 1996, vol. 271, pp. 216–219.

    Article  CAS  PubMed  Google Scholar 

  33. Bechtold, D.A., Rush, S.J., and Brown, I.R., Localization of the Heat-Shock Protein Hsp70 to the Synapse Following Hyperthermic Stress in the Brain, J. Neurochem., 2000, vol. 74, pp. 641–646.

    Article  CAS  PubMed  Google Scholar 

  34. Ohtsuka, K. and Suzuki, T., Roles of Molecular Chaperones in the Nervous System, Brain Res. Bull., 2000, vol. 53, pp. 141–146.

    Article  CAS  PubMed  Google Scholar 

  35. Mokrushin, A.A., Pavlinova, L.I., Guzhova, I.V., and Margulis, B.A., Protein of Heat Shock (Hsp70) Protects Activity of Glutamatergic Synaptic Transmission in the Rat Olfactory Brain Cortex in vitro from Severe Anoxia, Dokl. RAN, 2004, vol. 394, pp. 419–422.

    Google Scholar 

  36. Kelly, J.D., Noseworthy, P.A., Feder, M.E., Robertson, R.M., and Ramires, J.M., Thermal Preconditioning and Heat-Shock Protein 72 Preserve Synaptic Transmission during Thermal Stress, J. Neurochem., 2002, vol. 22, no. 1, p. RC193.

    Google Scholar 

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Correspondence to Yu. F. Pastukhov.

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Original Russian Text © Yu. F. Pastukhov, I. V. Ekimova, K. A. Khudik, I. V. Guzhova, 2008, published in Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, 2008, Vol. 44, No. 1, pp. 65–71.

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Pastukhov, Y.F., Ekimova, I.V., Khudik, K.A. et al. Protein 70 kDa in the control of sleep and thermoregulation. J Evol Biochem Phys 44, 74–81 (2008). https://doi.org/10.1134/S002209300801009X

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  • DOI: https://doi.org/10.1134/S002209300801009X

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