Hypoxia pp 21-38 | Cite as

Mammalian Hibernation

Transcriptional and translational controls
  • Kenneth B. Storey
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 543)

Abstract

Mammalian hibernation is an amazing strategy for winter survival. Animals sink into a deep torpor where metabolic rate is <5% of normal, body temperature falls to 0–5¡ãC, and physiological functions are strongly suppressed. Hibernation is a closely regulated process that includes multiple controls on gene transcription and protein translation, the primary subjects of this review. Recent studies by our lab and others have used multiple techniques of gene discovery, including cDNA array screening, to identify genes that are up-regulated in hibernation and continuing studies are tracing the functions of the encoded proteins and the signal transduction systems that regulate expression. For example, up-regulation of fatty acid binding proteins during hibernation facilitates the switch to a primary dependence on lipid fuels by nearly all organs and new studies have shown that up-regulation is mediated by the PPARy transcription factor and its co-activator, PGC-1. Several hypoxia-related genes including HIF-1¦Á are also up-regulated during hibernation suggesting a role for this transcription factor in mediating adaptive responses for hibernation. Controls on mRNA translation during hibernation accomplish two goals: a general strong suppression of protein synthesis that contributes to energy savings and the selected synthesis of a few specific proteins. These goals are accomplished by mechanisms that include reversible phosphorylation controls on ribosomal initiation and elongation factors and differential distribution of individual mRNA species between polysome and monosome fractions. Studies of gene expression, protein synthesis regulation, controls on fuel metabolism, and signal transduction pathways are combining to produce an integrated model of the biochemical regulation of hibernation.

Key Words

metabolic rate depression gene expression cDNA arrays signal transduction fatty acid binding protein 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Andrews MT, Squire TL, Bowen CM, and Rollins MB. Low-temperature carbon utilization is regulated by novel gene activity in the heart of a hibernating animal. Proc Natl Acad Sci USA 95: 8392–8397, 1998.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Barros RCH, Zimmer ME, Branco LGS, and Milsom WK. Hypoxic metabolic response of the golden-mantled ground squirrel. J Appl Physiol 91: 603–612, 2001.PubMedGoogle Scholar
  3. 3.
    Berger J, and Moller DE. The mechanisms of action of PPARs. Annu Rev Med 53: 409–435, 2002.PubMedCrossRefGoogle Scholar
  4. 4.
    Boyer BB, Barnes BM, Lowell BB, and Grujic D. Differential regulation of uncoupling protein gene homologues in multiple tissues of hibernating ground squirrels. Am J Physiol 275: R1232–R1238, 1998.PubMedGoogle Scholar
  5. 5.
    Burlington RF, Bowers WD, Daum RC, and Ashbaugh P. Ultrastructure changes in heart tissue during hibernation. Cryobiology 9: 224–228, 1972.PubMedCrossRefGoogle Scholar
  6. 6.
    Buzadzic B, Spasic MB, Saicic ZS, Radojicic R, Petrovic V M, and Halliwell B. Antioxidant defenses in the ground squirrel Citellus citellus. 1. The effect of hibernation. Free Rad Biol Med 9:407–413, 1990.PubMedCrossRefGoogle Scholar
  7. 7.
    Chen Y, Matsushita M, Nairn AC, Damuni Z, Cai D, Frerichs KU, and Hallenbeck JM. Mechanisms for increased levels of phosphorylation of elongation factor-2 during hibernation in ground squirrels. Biochemistry 40: 11565–11570, 2001.PubMedCrossRefGoogle Scholar
  8. 8.
    DeGracia DJ, Kumar R, Owen CR, Krause GS, and White BC. Molecular pathways of protein synthesis inhibition during brain reperfusion: implications for neuronal survival or death. J Cereb Blood Flow Metab 22: 127–141, 2002.PubMedCrossRefGoogle Scholar
  9. 9.
    Eddy SF, and Storey KB. Dynamic use of cDNA arrays: heterologous probing for gene discovery and exploration of animal adaptations in stressful environments. In: Cell and Molecular Responses to Stress, edited by Storey KB and Storey JM. Amsterdam: Elsevier Press, 2002, vol. 3, p. 297–325.Google Scholar
  10. 10.
    Fahlman A, Storey JM, and Storey KB. Gene up-regulation in heart during mammalian hibernation. Cryobiology 40: 332–342, 2000.PubMedCrossRefGoogle Scholar
  11. 11.
    Frerichs KU, Smith CB, Brenner M, DeGracia DJ, Krause GS, Marrone L, Dever TE, and Hallenbeck JM. Suppression of protein synthesis in brain during hibernation involves inhibition of protein initiation and elongation. Proc Natl Acad Sci USA 95: 14511–14516, 1998.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Gingras AC, Raught B, and Sonenbert N. eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation. Ann Rev Biochem 68: 913–963, 1999.PubMedCrossRefGoogle Scholar
  13. 13.
    Gorham DA, Bretscher A, and Carey HV. Hibernation induces expression of moesin in intestinal epithelia cells. Cryobiology 37: 146–154, 1998.PubMedCrossRefGoogle Scholar
  14. 14.
    Hermes-Lima M, Storey JM, and Storey KB. Antioxidant defenses and animal adaptation to oxygen availability during environmental stress. In: Cell and Molecular Responses to Stress edited by Storey KB and Storey JM. Amsterdam: Elsevier Press, 2001, vol. 2, p. 263–287.Google Scholar
  15. 15.
    Hittel D, and Storey KB. Differential expression of adipose and heart type fatty acid binding proteins in hibernating ground squirrels. Biochim Biophys Acta 1522: 238–243, 2001.PubMedCrossRefGoogle Scholar
  16. 16.
    Hittel D, and Storey KB. Differential expression of mitochondria-encoded genes in a hibernating mammal. J Exp Biol 205: 1625–1631, 2002.PubMedGoogle Scholar
  17. 17.
    Hittel D, and Storey KB. The translation status of differentially expressed mRNAs in the hibernating thirteen-lined ground squirrel ( Spermophilus tridecemlineatus ). Arch Biochem Biophys 401:244–254, 2002.PubMedCrossRefGoogle Scholar
  18. 18.
    Knight JE, Narus EN, Martin SL, Jacobson A, Barnes BM, and Boyer BB. mRNA stability and polysome loss in hibernating Arctic ground squirrels (Spermophilus parryii). Mol Cell Biol 20: 6374–6379, 2000.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Lang KJD, Kappel A, and Goodall GJ. Hypoxia-inducible factor-lα mRNA contains an internal ribosome entry site that allows efficient translation during normoxia and hypoxia. Mol Biol Cell 13: 1792–1801, 2002.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    McCarron RM, Sieckmann DG, Yu EZ, Frerichs K, and Hallenbeck JM. Hibernation, a state of natural tolerance to profound reduction in organ blood flow and oxygen delivery capacity. In: Molecular Mechanisms of Metabolic Arrest, edited by Storey, KB. Oxford: BIOS Scientific Publishers, 2001, p. 23–42.Google Scholar
  21. 21.
    Milsom WK. Control of breathing in hibernating mammals. In: Physiological Adaptations of Vertebrates: Respiration, Circulation and Metabolism, edited by Wood SC, Weber RE, Hargens AR, and Millard RW. NY: Marcel Dekker, 1992, p. 119–148.Google Scholar
  22. 22.
    Srere HK, Belke D, Wang LCH, and Martin SL. ¦Á2-Macroglobulin gene expression during hibernation in ground squirrels is independent of acute phase response. Am J Physiol 268: R1507–R1512, 1995.PubMedGoogle Scholar
  23. 23.
    Storey KB. Metabolic regulation in mammalian hibernation: enzyme and protein adaptations. Comp Biochem Physiol A 118: 1115–1124, 1997.CrossRefGoogle Scholar
  24. 24.
    Storey KB. Natural hypothermic preservation: the mammalian hibernator. J Cell Preserv Technol 1:3–16, 2002.CrossRefGoogle Scholar
  25. 25.
    Storey KB, and Storey JM. Facultative metabolic rate depression: molecular regulation and biochemical adaptation in anaerobiosis, hibernation and estivation. Quart Rev Biol 65: 145–174, 1990.PubMedCrossRefGoogle Scholar
  26. 26.
    Storey KB, and Storey JM. Metabolic rate depression in animals:transcriptional and trnaslational controls. Biol Rev in press, 2003.Google Scholar
  27. 27.
    Urakami Y, Okuda M, Saito H, and Inui K. Hormonal regulation of organic cation transporter OCT2 expression in rat kidney. FEBS Lett 473: 173–176, 2000.PubMedCrossRefGoogle Scholar
  28. 28.
    Van Breukelen F, and Martin SL. Translational initiation is uncoupled from elongation at 18¡ãC during mammalian hibernation. Am J Physiol 281: R1374–R1379, 2001.Google Scholar
  29. 29.
    Vayada ME, Londraville RL, Cashon RE, Costello L, and Sidell B. Two distinct types of fatty acid-binding protein are expressed in heart ventricle of Antarctic teleost fishes. Biochem J 330: 375–382, 1998.Google Scholar
  30. 30.
    Vogel Hertzel A, and Bernlohr, DA. The mammalian fatty acid binding protein multigene family: molecular and genetic insights into function. Trends Endocrinol Metab 11: 175–180, 2000.CrossRefGoogle Scholar
  31. 31.
    Wang LCH, and Lee TF. Torpor and hibernation in mammals: metabolic, physiological, and biochemical adaptations. In: Handbook of Physiology: Environmental Physiology edited by Fregley MJ, and Blatteis CM. NY: Oxford University Press, 1996, sect. 4, vol. 1, p. 507–532.Google Scholar
  32. 32.
    Wenger RH. Mammalian oxygen sensing, signalling and gene regulation. J Exp Biol 203: 1253–1263, 2000.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Kenneth B. Storey

There are no affiliations available

Personalised recommendations