Dormancy and Resistance in Harsh Environments pp 227-252

Part of the Topics in Current Genetics book series (TCG, volume 21)

Mammalian Hibernation: Physiology, Cell Signaling, and Gene Controls on Metabolic Rate Depression

  • Kenneth B. Storey
  • Gerhard Heldmaier
  • Mark H. Rider
Chapter

Abstract

During the hibernating season, small mammals may suppress their metabolic rate during cyclic periods of deep torpor by as much as 99% as compared with normothermia. Endocrine regulation of metabolic depression is still poorly understood but recent studies suggest involvement of hormones including iodothyronamine, leptin, and ghrelin. At the intracellular level, suppression of many metabolic functions is achieved via reversible protein phosphorylation of metabolic enzymes, protein synthesis translation factors, and ion pumps. Potential roles for signaling enzymes such as the AMP-activated protein kinase in the coordination of metabolic suppression have been analyzed. Recent advances in the control of global gene expression have identified participating mechanisms including histone modifications that affect chromatin structure, SUMOylation to suppress transcription factor action, and differential regulation of mRNA transcripts by interaction with microRNA species. However, despite global transcriptional suppression, selected transcription factors are active during torpor bouts triggering the up-regulation of specific genes that serve the hibernation phenotype.

References

  1. Abnous K, Storey KB (2007) Regulation of skeletal muscle creatine kinase in a hibernating mammal. Arch Biochem Biophys 467:10–19PubMedCrossRefGoogle Scholar
  2. Abnous K, Storey KB (2008) Skeletal muscle hexokinase: regulation in mammalian hibernation. Mol Cell Biochem 319:41–50PubMedCrossRefGoogle Scholar
  3. Abnous K, Dieni CA, Storey KB (2008) Regulation of Akt during hibernation in Richardson’s ground squirrels. Biochim Biophys Acta 1780:185–193PubMedCrossRefGoogle Scholar
  4. Andrews MT, Squire TL, Bowen CM, Rollins MB (1998) Low-temperature carbon utilization is regulated by novel gene activity in the heart of a hibernating mammal. Proc Natl Acad Sci USA 95:8392–8397PubMedCrossRefGoogle Scholar
  5. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism and function. Cell 116:281–297PubMedCrossRefGoogle Scholar
  6. Bartrons M, Ortega E, Obach M, Calve MN, Navarro-Sabate A, Bartrons R (2004) Activation of AMP-dependent protein kinase by hypoxia and hypothermia in the liver of frog Rana perezi. Cryobiology 49:190–194PubMedCrossRefGoogle Scholar
  7. Berriel Diaz M, Lange M, Heldmaier G, Klingenspor M (2004) Depression of transcription and translation during daily torpor in the Djungarian hamster (Phodopus sungorus). J Comp Physiol B 174:495–502PubMedCrossRefGoogle Scholar
  8. Bhaumik SR, Smith E, Shilatifard A (2007) Covalent modifications of histones during development and disease pathogenesis. Nat Struct Mol Biol 14:1008–1016PubMedCrossRefGoogle Scholar
  9. Blackstone E, Morrison M, Roth MB (2005) H2S induces a suspended animation-like state in mice. Science 308:518PubMedCrossRefGoogle Scholar
  10. Bocharova LS, Gordon RY, Arkhipov VI (1992) Uridine uptake and RNA synthesis in the brain of torpid and awakened ground squirrels. Comp Biochem Physiol B 101:189–192PubMedGoogle Scholar
  11. Brauch KM, Dhruv ND, Hanse EA, Andrews MT (2005) Digital transcriptome analysis indicates adaptive mechanisms in the heart of a hibernating mammal. Physiol Genomics 23:227–234PubMedCrossRefGoogle Scholar
  12. Braulke LJ, Klingenspor M, DeBarber A, Tobias SC, Grandy DK, Scanlan TS, Heldmaier G (2008) 3-Iodothyronamine: a novel hormone controlling the balance between glucose and lipid utilisation. J Comp Physiol B 178:167–177PubMedCrossRefGoogle Scholar
  13. Buck CL, Barnes BM (2000) Effects of ambient temperature on metabolic rate, respiratory quotient, and torpor in an Arctic hibernator. Am J Physiol 279:R255–R262Google Scholar
  14. Carey HV, Andrews MT, Martin SL (2003) Mammalian hibernation: cellular and molecular responses to depressed metabolism and low temperature. Physiol Rev 83:1153–1181PubMedGoogle Scholar
  15. Chae HZ, Kim HJ, Kang SW, Rhee SG (1999) Characterization of three isoforms of mammalian peroxiredoxin that reduce peroxides in the presence of thioredoxin. Diabetes Res Clin Pract 45:101–112PubMedCrossRefGoogle Scholar
  16. Chan JA, Krichevsky AM, Kosik KS (2005) MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 65:6029–6033PubMedCrossRefGoogle Scholar
  17. Chen JF, Mandel EM, Thomson JM, Wu Q, Callis TE, Hammond SM, Conlon FL, Wang DZ (2006) The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet 38:228–233PubMedCrossRefGoogle Scholar
  18. Chen J, Yuan L, Sun M, Zhang L, Zhang S (2008) Screening of hibernation-related genes in the brain of Rhinolophus ferrumequinum during hibernation. Comp Biochem Physiol B Biochem Mol Biol 149:388–393PubMedCrossRefGoogle Scholar
  19. Cheng SW, Fryer LG, Carling D, Shepherd PR (2004) Thr2446 is a novel mammalian target of rapamycin (mTOR) phosphorylation site regulated by nutrient status. J Biol Chem 279:15719–15722PubMedCrossRefGoogle Scholar
  20. Cheng AM, Byrom MW, Shelton J, Ford LP (2005) Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res 33:1290–1297PubMedCrossRefGoogle Scholar
  21. Crawford FI, Hodgkinson CL, Ivanova EA, Logunova LB, Evans GJ, Steinlechner S, Loudon AS (2007) The influence of torpor on cardiac expression of genes involved in the circadian clock and protein turnover in the Siberian hamster (Phodopus sungorus). Physiol Genom 31:521–530CrossRefGoogle Scholar
  22. Dark J, Miller DJ, Licht P, Zucker I (1996) Glucoprivation counteracts effects of testosterone on daily torpor in Djungarian hamsters. Am J Physiol 270:R398–R403PubMedGoogle Scholar
  23. Dausmann KH, Glos J, Ganzhorn JU, Heldmaier G (2005) Hibernation in the tropics: lessons from a primate. J Comp Physiol B 175:147–155PubMedCrossRefGoogle Scholar
  24. Dausmann KH, Glos J, Heldmaier G (2009) Energetics of tropical hibernation. J Comp Physiol B 179:345–357PubMedCrossRefGoogle Scholar
  25. Daval M, Diot-Dupuy F, Bazin R, Hainault I, Viollet B, Vaulont S, Hajduch E, Ferre P, Foufelle F (2005) Anti-lipolytic action of AMP-activated protein kinase in rodent adipocytes. J Biol Chem 280:25250–25257PubMedCrossRefGoogle Scholar
  26. Ding XC, Weiler J, Großhans H (2009) Regulating the regulators: mechanisms controlling the maturation of microRNAs. Trends Biotechnol 27:27–36PubMedCrossRefGoogle Scholar
  27. Drew KL, Tøien Ø, Rivera PM, Smith MA, Perry G, Rice ME (2002) Role of the antioxidant ascorbate in hibernation and warming from hibernation. Comp Biochem Physiol C 133:483–492Google Scholar
  28. Drew KL, Buck LC, Barnes BM, Christian SL, Rasley BT, Harris MB (2007) Central nervous system regulation of mammalian hibernation: implications for metabolic suppression and ischemia tolerance. J Neurochem 102:1713–1726PubMedCrossRefGoogle Scholar
  29. Eddy SF, Storey KB (2003) Differential expression of Akt, PPARγ, and PGC-1 during hibernation in bats. Biochem Cell Biol 81:269–274PubMedCrossRefGoogle Scholar
  30. Eddy SF, Storey KB (2004) Up-regulation of fatty acid-binding proteins during hibernation in the little brown bat, Myotis lucifugus. Biochim Biophys Acta 1676:63–70PubMedCrossRefGoogle Scholar
  31. Eddy SF, Storey KB (2007) p38MAPK regulation of transcription factor targets in muscle and heart of hibernating bats, Myotis lucifugus. Cell Biochem Funct 25:759–765PubMedCrossRefGoogle Scholar
  32. Eddy SF, Storey KB (2008) Comparative molecular physiological genomics. Heterologous probing of cDNA arrays. Methods Mol Biol 410:81–110PubMedCrossRefGoogle Scholar
  33. Eddy SF, McNally JD, Storey KB (2005) Up-regulation of a thioredoxin peroxidase-like protein, proliferation-associated gene, in hibernating bats. Arch Biochem Biophys 435:103–111PubMedCrossRefGoogle Scholar
  34. Ehrhardt N, Heldmaier G, Exner C (2005) Adaptive mechanisms during food restriction in Acomys russatus: the use of torpor for desert survival. J Comp Physiol B 175:193–200PubMedCrossRefGoogle Scholar
  35. Elvert R, Heldmaier G (2005) Cardiorespiratory and metabolic reactions during entrance into torpor in dormice, Glis glis. J Exp Biol 208:1373–1383PubMedCrossRefGoogle Scholar
  36. Epperson LE, Dahl TA, Martin SL (2004) Quantitative analysis of liver protein expression during hibernation in the golden-mantled ground squirrel. Mol Cell Proteomics 3:920–933PubMedCrossRefGoogle Scholar
  37. Fahlman A, Storey JM, Storey KB (2000) Gene up-regulation in heart during mammalian hibernation. Cryobiology 40:332–342PubMedCrossRefGoogle Scholar
  38. Florant GL, Heller HC (1977) CNS regulation of body temperature in euthermic and hibernating marmots (Marmota flaviventris). Am J Physiol 232:R203–R208PubMedGoogle Scholar
  39. Flynt AS, Lai EC (2008) Biological principles of microRNA-mediated regulation: shared themes amid diversity. Nat Rev Genet 9:831–842PubMedCrossRefGoogle Scholar
  40. Fraga MF, Esteller M (2007) Epigenetics and aging: the targets and the marks. Trends Genet 23:413–418PubMedCrossRefGoogle Scholar
  41. Frerichs KU, Smith CB, Brenner M, DeGracia DJ, Krause GS, Marrone L, Dever TE, Hallenbeck JM (1998) Suppression of protein synthesis in brain during hibernation involves inhibition of protein initiation and elongation. Proc Natl Acad Sci USA 95:14511–14516PubMedCrossRefGoogle Scholar
  42. Fujii G, Nakamura Y, Tsukamoto D, Ito M, Shiba T, Takamatsu N (2006) CpG methylation at the USF-binding site is important for the liver-specific transcription of the chipmunk HP-27 gene. Biochem J 395:203–209PubMedCrossRefGoogle Scholar
  43. Gammell P (2007) MicroRNAs: recently discovered key regulators of proliferation and apoptosis in animal cells. Cytotechnology 53:55–63PubMedCrossRefGoogle Scholar
  44. Gauthier MS, Miyoshi H, Souza SC, Cacicedo JM, Saha AK, Greenberg AS, Ruderman NB (2008) AMP-activated protein kinase is activated as a consequence of lipolysis in the adipocyte: potential mechanism and physiological relevance. J Biol Chem 283:16514–16524PubMedCrossRefGoogle Scholar
  45. Geiser F (1988) Reduction of metabolism during hibernation and daily torpor in mammals and birds: temperature effect or physiological inhibition? J Comp Physiol B 158:25–37PubMedCrossRefGoogle Scholar
  46. Geiser F (2004) Metabolic rate and body temperature reduction during hibernation and daily torpor. Annu Rev Physiol 66:239–274PubMedCrossRefGoogle Scholar
  47. Girdwood DW, Tatham MH, Hay RT (2004) SUMO and transcriptional regulation. Semin Cell Dev Biol 15:201–210PubMedCrossRefGoogle Scholar
  48. Gluck EF, Stephens N, Swoap SJ (2006) Peripheral ghrelin deepens torpor bouts in mice through the arcuate nucleus neuropeptide Y signaling pathway. Am J Physiol 291:R1303–R1309Google Scholar
  49. Gorham DA, Bretscher A, Carey HV (1998) Hibernation induces expression of moesin in intestinal epithelial cells. Cryobiology 37:146–154PubMedCrossRefGoogle Scholar
  50. Guppy M, Withers P (1999) Metabolic depression in animals: physiological perspectives and biochemical generalizations. Biol Rev 74:1–40PubMedCrossRefGoogle Scholar
  51. Gutman R, Choshniak I, Kronfeld-Schor N (2006) Defending body mass during food restriction in Acomys russatus: a desert rodent that does not store food. Am J Physiol 290:R881–R891Google Scholar
  52. Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, Turk BE, Shaw RJ (2008) AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell 30:214–226PubMedCrossRefGoogle Scholar
  53. Hardie DG (2004) The AMP-activated protein kinase pathway – new players upstream and downstream. J Cell Sci 117:5479–5487PubMedCrossRefGoogle Scholar
  54. Hardie DG (2007) AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 8:774–785PubMedCrossRefGoogle Scholar
  55. Hardie DG, Carling D, Carlson M (1998) The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell? Annu Rev Biochem 67:821–855PubMedCrossRefGoogle Scholar
  56. Heldmaier G, Elvert R (2004) How to enter torpor: thermodynamic and physiological mechanisms of metabolic depression. In: Barnes BM, Carey HV (eds) Life in the cold: evolution, mechanisms, adaptation, and application. Biological Papers of the University of Alaska, #27, Fairbanks, pp183–198Google Scholar
  57. Heldmaier G, Ruf T (1992) Body temperature and metabolic rate during natural hypothermia in endotherms. J Comp Physiol B 162:696–706PubMedCrossRefGoogle Scholar
  58. Heldmaier G, Klingenspor M, Werneyer M, Lampi BJ, Brooks SP, Storey KB (1999) Metabolic adjustments during daily torpor in the Djungarian hamster. Am J Physiol 276:E896–E906PubMedGoogle Scholar
  59. Heldmaier G, Ortmann S, Elvert R (2004) Natural hypometabolism during hibernation and daily torpor in mammals. Respir Physiol Neurobiol 141:317–329PubMedCrossRefGoogle Scholar
  60. Hittel D, Storey KB (2002a) The translation state of differentially expressed mRNAs in the hibernating thirteen-lined ground squirrel (Spermophilus tridecemlineatus). Arch Biochem Biophys 401:244–254PubMedCrossRefGoogle Scholar
  61. Hittel DS, Storey KB (2002b) Differential expression of mitochondria-encoded genes in a hibernating mammal. J Exp Biol 205:1625–1631PubMedGoogle Scholar
  62. Horman S, Browne G, Krause U, Patel J, Vertommen D, Bertrand L, Lavoinne A, Hue L, Proud C, Rider M (2002) Activation of AMP-activated protein kinase leads to the phosphorylation of elongation factor 2 and an inhibition of protein synthesis. Curr Biol 12:1419–1423PubMedCrossRefGoogle Scholar
  63. Horman S, Beauloye C, Vertommen D, Vanoverschelde JL, Hue L, Rider MH (2003) Myocardial ischemia and increased heart work modulate the phosphorylation state of eukaryotic elongation factor-2. J Biol Chem 278:41970–41976PubMedCrossRefGoogle Scholar
  64. Horman S, Hussain N, Dilworth SM, Storey KB, Rider MH (2005) Evaluation of the role of AMP-activated protein kinase and its downstream targets in mammalian hibernation. Comp Biochem Physiol B Biochem Mol Biol 142:374–382PubMedCrossRefGoogle Scholar
  65. Hue L, Rider MH (2007) The AMP-activated protein kinase: more than an energy sensor. Essays Biochem 43:121–137PubMedCrossRefGoogle Scholar
  66. Inoki K, Zhu T, Guan KL (2003) TSC2 mediates cellular energy response to control cell growth and survival. Cell 115:577–590PubMedCrossRefGoogle Scholar
  67. Ishii T, Yanagawa T (2007) Stress-induced peroxiredoxins. Subcell Biochem 44:375–384PubMedCrossRefGoogle Scholar
  68. Jiang Q, Wang Y, Hao Y, Juan L, Teng M, Zhang X, Li M, Wang G, Liu Y (2008) miR2 Disease: a manually curated database for microRNA deregulation in human disease. Nucleic Acids Res 37:D98–D104. doi:10.1093/nar/gkn714PubMedCrossRefGoogle Scholar
  69. Jibb LA, Richards JG (2008) AMP-activated protein kinase activity during metabolic rate depression in the hypoxic goldfish, Carassius auratus. J Exp Biol 211:3111–3122PubMedCrossRefGoogle Scholar
  70. Kahn BB, Alquier T, Carling D, Hardie DG (2005) AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 1:15–25PubMedCrossRefGoogle Scholar
  71. Kim E, Du L, Bregman DB, Warren SL (1997) Splicing factors associate with hyperphosphorylated RNA polymerase II in the absence of pre-mRNA. J Cell Biol 136:19–28PubMedCrossRefGoogle Scholar
  72. Knight JE, Narus EN, Martin SL, Jacobson A, Barnes BM, Boyer BB (2000) mRNA stability and polysome loss in hibernating Arctic ground squirrels (Spermophilus parryii). Mol Cell Biol 20:6374–6379PubMedCrossRefGoogle Scholar
  73. Lee YJ, Miyake S, Wakita H, McMullen DC, Azuma Y, Auh S, Hallenbeck JM (2007) Protein SUMOylation is massively increased in hibernation torpor and is critical for the cytoprotection provided by ischemic preconditioning and hypothermia in SHSY5Y cells. J Cereb Blood Flow Metabol 27:950–962Google Scholar
  74. Lee K, Park JY, Yoo W, Gwag T, Lee JW, Byun MW, Choi I (2008) Overcoming muscle atrophy in a hibernating mammal despite prolonged disuse in dormancy: proteomic and molecular assessment. J Cell Biochem 104:642–656PubMedCrossRefGoogle Scholar
  75. Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS, Johnson JM (2005) Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433:769–773PubMedCrossRefGoogle Scholar
  76. Lyman CP (1958) Oxygen consumption, body temperature and heart rate of woodchucks entering hibernation. Am J Physiol 194:83–91PubMedGoogle Scholar
  77. Lyman CP, O’Brien RC (1960) Circulatory changes in the thirteen-lined ground squirrel during the hibernation cycle. Bull Mus Comp Zool 124:353–372Google Scholar
  78. MacDonald JA, Storey KB (1998) cAMP-dependent protein kinase from brown adipose tissue: temperature effects on kinetic properties and enzyme role in hibernating ground squirrels. J Comp Physiol B 168:513–525PubMedCrossRefGoogle Scholar
  79. MacDonald JA, Storey KB (1999) Regulation of ground squirrel Na+K+-ATPase activity by reversible phosphorylation during hibernation. Biochem Biophys Res Commun 254:424–429PubMedCrossRefGoogle Scholar
  80. MacDonald JA, Storey KB (2005) Mitogen-activated protein kinases and selected downstream targets display organ-specific responses in the hibernating ground squirrel. Int J Biochem Cell Biol 37:679–691PubMedCrossRefGoogle Scholar
  81. Mack GS (2006) Epigenetic cancer therapy makes headway. J Natl Cancer Inst 98:1443–1444PubMedCrossRefGoogle Scholar
  82. Mamady H, Storey KB (2006) Up-regulation of the endoplasmic reticulum molecular chaperone GRP78 during hibernation in thirteen-lined ground squirrels. Mol Cell Biochem 292:89–98PubMedCrossRefGoogle Scholar
  83. Mamady H, Storey KB (2008) Coping with stress: expression of ATF4, ATF6 and downstream targets in organs of hibernating ground squirrels. Arch Biochem Biophys 477:77–85PubMedCrossRefGoogle Scholar
  84. Martin SL, Epperson LE, Rose JC, Kurtz CC, Ané C, Carey HV (2008) Proteomic analysis of the winter-protected phenotype of hibernating ground squirrel intestine. Am J Physiol 295:R316–R328Google Scholar
  85. Matejkova O, Mustard KJ, Sponarova J, Flachs P, Rossmeisl M, Miksik I, Thomason-Hughes M, Hardie GD, Kopecky J (2004) Possible involvement of AMP-activated protein kinase in obesity resistance induced by respiratory uncoupling in white fat. FEBS Lett 569:245–248PubMedCrossRefGoogle Scholar
  86. Milsom WK, Zimmer MB, Harris MB (2001) Vagal control of cardiorespiratory function in hibernation. Exp Physiol 86:791–796PubMedCrossRefGoogle Scholar
  87. Morin P, Storey KB (2005) Cloning and expression of hypoxia-inducible factor 1α from the hibernating ground squirrel, Spermophilus tridecemlineatus. Biochim Biophys Acta 1729:32–40PubMedCrossRefGoogle Scholar
  88. Morin P, Storey KB (2006) Evidence for a reduced transcriptional state during hibernation in ground squirrels. Cryobiology 53:310–318PubMedCrossRefGoogle Scholar
  89. Morin P, Storey KB (2007) Antioxidant defense in hibernation: cloning and expression of peroxiredoxins from hibernating ground squirrels, Spermophilus tridecemlineatus. Arch Biochem Biophys 461:59–65PubMedCrossRefGoogle Scholar
  90. Morin P, Dubuc A, Storey KB (2008a) Differential expression of microRNA species in organs of hibernating ground squirrels: a role in translational suppression during torpor. Biochim Biophys Acta 1779:628–633PubMedCrossRefGoogle Scholar
  91. Morin P, Ni Z, McMullen DC, Storey KB (2008b) Expression of Nrf2 and its downstream gene targets in hibernating thirteen-lined ground squirrels, Spermophilus tridecemlineatus. Mol Cell Biochem 312:121–129PubMedCrossRefGoogle Scholar
  92. Mulligan JD, Gonzalez AA, Stewart AM, Carey HV, Saupe KW (2007) Upregulation of AMPK during cold exposure occurs via distinct mechanisms in brown and white adipose tissue of the mouse. J Physiol 580:677–684PubMedCrossRefGoogle Scholar
  93. Nicol SC, Andersen NA (2000) Patterns of hibernation of echidnas in Tasmania. In: Heldmaier G, Klingenspor M (eds) Life in the Cold. Springer, Heidelberg, pp 21–28Google Scholar
  94. Ortmann S, Heldmaier G (2000) Regulation of body temperature and energy requirements of hibernating alpine marmots (Marmota marmota). Am J Physiol 278:R698–R704Google Scholar
  95. Osborne PG, Gao B, Hashimoto M (2004) Determination in vivo of newly synthesized gene expression in hamsters during phases of the hibernation cycle. Jpn J Physiol 54:295–305PubMedCrossRefGoogle Scholar
  96. Proud CG (2007) Signalling to translation: how signal transduction pathways control the protein synthetic machinery. Biochem J 403:217–234PubMedCrossRefGoogle Scholar
  97. Rider MH (2008) Dealing with energy stress in hypometabolic states: role of the AMP-activated protein kinase. In: Lovegrove BG, McKechnie AE (eds) Hypometabolism in animals: torpor, hibernation and cryobiology. University of KwaZulu-Natal, Pietermaritzburg, pp 75–82Google Scholar
  98. Rider MH, Hussain N, Horman S, Dilworth SM, Storey KB (2006) Stress-induced activation of the AMP-activated protein kinase in the freeze-tolerant frog Rana sylvatica. Cryobiology 53:297–309PubMedCrossRefGoogle Scholar
  99. Rider MH, Hussain N, Dilworth SM, Storey KB (2009) Phosphorylation of translation factors in response to anoxia in turtles, Trachemys scripta elegans: role of the AMP-activated protein kinase and target of rapamycin signalling pathways. Mol Cell Biochem 332:207–213PubMedCrossRefGoogle Scholar
  100. Sanders MJ, Grondin PO, Hegarty BD, Snowden MA, Carling D (2007) Investigating the mechanism for AMP activation of the AMP-activated protein kinase cascade. Biochem J 403:139–148PubMedCrossRefGoogle Scholar
  101. Sarraf SA, Stancheva I (2004) Methyl-CpG binding protein MBD1 couples histone H3 methylation at lysine 9 by SETDB1 to DNA replication and chromatin assembly. Mol Cell 15:595–605PubMedCrossRefGoogle Scholar
  102. Scanlan TS, Suchland KL, Hart ME, Chiellini G, Huang Y, Kruzich PJ, Frascarelli S, Crossley DA, Bunzow JR, Ronca-Testoni S, Lin ET, Hatton D, Zucchi R, Grandy DK (2004) 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone. Nat Med 10:638–642PubMedCrossRefGoogle Scholar
  103. Schroder M, Kaufman RJ (2005) The mammalian unfolded protein response. Annu Rev Biochem 74:739–789PubMedCrossRefGoogle Scholar
  104. Semenza GL (2003) Targeting HIF-1 for cancer therapy. Nat Rev Cancer 3:721–732PubMedCrossRefGoogle Scholar
  105. Song X, Körtner G, Geiser F (1997) Thermal relations of metabolic rate reduction in a hibernating marsupial. Am J Physiol 273:R2097–R2104PubMedGoogle Scholar
  106. Stenslokken KO, Ellefsen S, Stecyk JA, Dahl MB, Nilsson GE, Vaage JI (2008) Differential regulation of AMP-activated kinase and AKT kinase in response to oxygen availability in crucian carp (Carassius carassius). Am J Physiol 295:R1803–R1814Google Scholar
  107. Storey KB (1997) Metabolic regulation in mammalian hibernation: enzyme and protein adaptations. Comp Biochem Physiol 118:1115–1124CrossRefGoogle Scholar
  108. Storey KB (2004) Cold, ischemic organ preservation: lessons from natural systems. J Investig Med 52:315–322PubMedCrossRefGoogle Scholar
  109. Storey KB (2008) Beyond gene chips: transcription factor profiling in freeze tolerance. In: Lovegrove BG, McKechnie AE (eds) Hypometabolism in animals: hibernation, torpor and cryobiology. University of KwaZulu-Natal, Pietermaritzburg, pp 101–108Google Scholar
  110. Storey KB, Storey JM (2004) Metabolic rate depression in animals: transcriptional and translational controls. Biol Rev Camb Philos Soc 79:207–233PubMedCrossRefGoogle Scholar
  111. Storey KB, Storey JM (2007) Putting life on ‘pause’ – molecular regulation of hypometabolism. J Exp Biol 210:1700–1714PubMedCrossRefGoogle Scholar
  112. Swoap SJ (2008) The pharmacology and molecular mechanisms underlying temperature regulation and torpor. Biochem Pharmacol 76:817–824PubMedCrossRefGoogle Scholar
  113. Swoap SJ, Rathvon M, Gutilla M (2007) AMP does not induce torpor. Am J Physiol 293:R468–R473CrossRefGoogle Scholar
  114. Tate PH, Bird AP (1993) Effects of DNA methylation on DNA-binding proteins and gene expression. Curr Opin Genet Dev 3:226–231PubMedCrossRefGoogle Scholar
  115. Van Breukelen F, Martin SL (2001) Translational initiation is uncoupled from elongation at 18°C during mammalian hibernation. Am J Physiol 281:R1374–R1379Google Scholar
  116. Van Breukelen F, Martin SL (2002) Reversible depression of transcription during hibernation. J Comp Physiol B 172:355–361PubMedCrossRefGoogle Scholar
  117. Van Breukelen F, Sonenberg N, Martin SL (2004) Seasonal and state-dependent changes of eIF4E and 4E-BP1 during mammalian hibernation: implications for the control of translation during torpor. Am J Physiol 287:R349–R353Google Scholar
  118. Wang LCH (1979) Time patterns and metabolic rates of natural torpor in the Richardson’s ground squirrel. Can J Zool 57:149–155CrossRefGoogle Scholar
  119. Wieser W, Krumschnabel G (2001) Hierarchies of ATP-consuming processes: direct compared with indirect measurements, and comparative aspects. Biochem J 355:389–395PubMedCrossRefGoogle Scholar
  120. Williams DR, Epperson LE, Li W, Hughes MA, Taylor R, Rogers J, Martin SL, Cossins AR, Gracey AY (2005) Seasonally hibernating phenotype assessed through transcript screening. Physiol Genomics 24:13–22PubMedCrossRefGoogle Scholar
  121. Wilz M, Heldmaier G (2000) Comparison of hibernation, estivation and daily torpor in the edible dormouse, Glis glis. J Comp Physiol B 170:511–521PubMedCrossRefGoogle Scholar
  122. Witters LA, Kemp BE, Means AR (2006) Chutes and Ladders: the search for protein kinases that act on AMPK. Trends Biochem Sci 31:13–16PubMedCrossRefGoogle Scholar
  123. Xue B, Kahn BB (2006) AMPK integrates nutrient and hormonal signals to regulate food intake and energy balance through effects in the hypothalamus and peripheral tissues. J Physiol 574:73–83PubMedCrossRefGoogle Scholar
  124. Zhang J, Kaasik K, Blackburn MR, Lee CC (2006) Constant darkness is a circadian metabolic signal in mammals. Nature 439:340–343PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • Kenneth B. Storey
    • 1
  • Gerhard Heldmaier
    • 2
  • Mark H. Rider
    • 3
  1. 1.Institute of BiochemistryCarleton UniversityOttawaCanada
  2. 2.Faculty of BiologyMarburg UniversityMarburgGermany
  3. 3.Université catholique de Louvain and de Duve InstituteBrusselsBelgium

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