Introduction to Mammalian Circadian Clock System

  • Chapter
  • First Online:
Circadian Pharmacokinetics
  • 525 Accesses

Abstract

Organisms on Earth are dictated by circadian changes (e.g., sunlight, humidity, and temperature) in the environment caused by the planet’s rotation around its own axis. All forms of life have evolved biological clocks to adapt (and to synchronize) their physiology and behaviors to circadian environmental changes. This adaptation results in circadian rhythms (with a period of ~24 h) in many physiological and behavioral processes such as the sleep–wake cycle, body temperature, energy metabolism, cognitive performance, and hormonal release. Perturbation of circadian rhythms is associated with various pathologic conditions, including cancers, metabolic syndromes, cardiovascular diseases, sleep disorder, and depression. On the other hand, many diseases present circadian rhythms in flares of symptoms. Thus, it is of great interest to investigate circadian rhythms in depth, which would help to find means to combat diseases and to optimize drug treatment. In this chapter, we introduce mammalian circadian clock system and discuss the role of circadian clock in human health.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Dunlap JC (1999) Molecular bases for circadian clocks. Cell 96:271–290

    Article  CAS  Google Scholar 

  2. Cermakian N, Sassone-Corsi P (2000) Multilevel regulation of the circadian clock. Nat Rev Mol Cell Biol 1:59–67

    Article  CAS  Google Scholar 

  3. Mohawk JA, Green CB et al (2012) Central and peripheral circadian clocks in mammals. Annu Rev Neurosci 35:445–462

    Article  CAS  Google Scholar 

  4. Bechtold DA, Gibbs JE et al (2010) Circadian dysfunction in disease. Trends Pharmacol Sci 31:191–198

    Article  CAS  Google Scholar 

  5. Sahar S, Sassone-Corsi P (2009) Metabolism and cancer: the circadian clock connection. Nat Rev Cancer 9:886–896

    Article  CAS  Google Scholar 

  6. Dibner C, Schibler U (2015) Circadian timing of metabolism in animal models and humans. J Intern Med 277:513–527

    Article  CAS  Google Scholar 

  7. Cortelli P (2015) Chronomedicine: a necessary concept to manage human diseases. Sleep Med Rev 21:1–2

    Article  Google Scholar 

  8. Brandenberger G, Ehrhart J et al (2001) Inverse coupling between ultradian oscillations in delta wave activity and heart rate variability during sleep. Clin Neurophysiol 112(6):992–996

    Article  CAS  Google Scholar 

  9. Stupfel M, Pletan Y (1983) Respiratory ultradian rhythms of mean and low frequencies: a comparative physiological approach. Chronobiologia 10(3):283–292

    CAS  Google Scholar 

  10. Edmunds LN, Tay DE (1982) Circadian and infradian rhythms. In: The biology of Euglena, vol 3. Academic Press, New York, pp 53–140

    Google Scholar 

  11. Thimonier J (1981) Control of seasonal reproduction in sheep and goats by light and hormones. Reprod Fertil Suppl 30:33–45

    CAS  Google Scholar 

  12. Mitsui S, Yamaguchi S et al (2001) Antagonistic role of E4BP4 and PAR proteins in the circadian oscillatory mechanism. Genes Dev 15(8):995–1006

    Article  CAS  Google Scholar 

  13. Cedernaes J, Osler ME et al (2015) Acute sleep loss induces tissue-specific epigenetic and transcriptional alterations to circadian clock genes in men. J Clin Endocrinol Metab 100(9):E1255–E1261

    Article  Google Scholar 

  14. Hernández-Rosas F, López-Rosas CA et al (2020) Disruption of the molecular circadian clock and cancer: an epigenetic link. Biochem Genet 58(1):189–209

    Article  CAS  Google Scholar 

  15. Vitaterna MH, King DP et al (1994) Mutagenesis and map** of a mouse gene, clock, essential for circadian behavior. Science 264(5159):719–725

    Article  CAS  Google Scholar 

  16. King DP, Zhao Y et al (1997) Positional cloning of the mouse circadian clock gene. Cell 89(4):641–653

    Article  CAS  Google Scholar 

  17. Antoch MP, Song EJ et al (1997) Functional identification of the mouse circadian clock gene by transgenic BAC rescue. Cell 89(4):655–667

    Article  CAS  Google Scholar 

  18. Buhr ED, Takahashi JS (2013) Molecular components of the Mammalian circadian clock. Handb Exp Pharmacol 217:3–27

    Article  CAS  Google Scholar 

  19. Debruyne JP (2008) Oscillating perceptions: the ups and downs of the clock protein in the mouse circadian system. J Genet 87(5):437–446

    Article  CAS  Google Scholar 

  20. Yoo SH, Ko CH et al (2005) A noncanonical E-box enhancer drives mouse Period2 circadian oscillations in vivo. Proc Natl Acad Sci U S A 102(7):2608–2613

    Article  CAS  Google Scholar 

  21. Steeves TD, King DP et al (1999) Molecular cloning and characterization of the human clock gene: expression in the suprachiasmatic nuclei. Genomics 57(2):189–200

    Article  CAS  Google Scholar 

  22. Hirayama J, Sahar S et al (2007) Clock-mediated acetylation of BMAL1 controls circadian function. Nature 450(7172):1086–1090

    Article  CAS  Google Scholar 

  23. Doi M, Hirayama J et al (2006) Circadian regulator clock is a histone acetyltransferase. Cell 125(3):497–508

    Article  CAS  Google Scholar 

  24. Huang N, Chelliah Y et al (2012) Crystal structure of the heterodimeric clock: BMAL1 transcriptional activator complex. Science 337(6091):189–194

    Article  CAS  Google Scholar 

  25. Williams DL, Schwartz MW (2005) Out of synch: clock mutation causes obesity in mice. Cell Metab 1(6):355–356

    Article  CAS  Google Scholar 

  26. Garaulet M, Madrid JA (2009) Chronobiology, genetics and metabolic syndrome. Curr Opin Lipidol 20(2):127–134

    Article  CAS  Google Scholar 

  27. Sookoian S, Castaño G et al (2007) Common genetic variations in clock transcription factor are associated with nonalcoholic fatty liver disease. World J Gastroenterol 13(31):4242–4248

    Article  CAS  Google Scholar 

  28. Garaulet M, Corbalán MD et al (2010) Clock gene is implicated in weight reduction in obese patients participating in a dietary programme based on the Mediterranean diet. Int J Obes 34(3):516–523

    Article  CAS  Google Scholar 

  29. Sawant OB, Horton AM et al (2017) The circadian clock gene Bmal1 controls thyroid hormone-mediated spectral identity and cone photoreceptor function. Cell Rep 21(3):692–706

    Article  CAS  Google Scholar 

  30. Gréchez-Cassiau A, Rayet B et al (2008) The circadian clock component BMAL1 is a critical regulator of p21WAF1/CIP1 expression and hepatocyte proliferation. J Biol Chem 283(8):4535–4542

    Article  CAS  Google Scholar 

  31. Bunger MK, Wilsbacher LD et al (2000) Mop3 is an essential component of the master circadian pacemaker in mammals. Cell 103:1009–1017

    Article  CAS  Google Scholar 

  32. Harfmann BD, Schroder EA et al (2016) Muscle-specific loss of Bmal1 leads to disrupted tissue glucose metabolism and systemic glucose homeostasis. Skelet Muscle 6:12

    Article  CAS  Google Scholar 

  33. Marcheva B, Ramsey KM et al (2010) Disruption of the clock components clock and BMAL1 leads to hypoinsulinaemia and diabetes. Nature 466(7306):627–631

    Article  CAS  Google Scholar 

  34. DeBruyne JP, Weaver DR et al (2007) Peripheral circadian oscillators require clock. Curr Biol 17(14):R538–R539

    Article  CAS  Google Scholar 

  35. DeBruyne JP, Weaver DR et al (2007) Clock and NPAS2 have overlap** roles in the suprachiasmatic circadian clock. Nat Neurosci 10(5):543–545

    Article  CAS  Google Scholar 

  36. Debruyne JP, Noton E et al (2006) A clock shock: mouse clock is not required for circadian oscillator function. Neuron 50(3):465–477

    Article  CAS  Google Scholar 

  37. Baggs JE, Price TS et al (2009) Network features of the mammalian circadian clock. PLoS Biol 7(3):e52

    Article  CAS  Google Scholar 

  38. Huang ZJ, Edery I et al (1993) PAS is a dimerization domain common to Drosophila period and several transcription factors. Nature 364(6434):259–262

    Article  CAS  Google Scholar 

  39. Lindebro MC, Poellinger L et al (1995) Protein-protein interaction via PAS domains: role of the PAS domain in positive and negative regulation of the bHLH/PAS dioxin receptor-Arnt transcription factor complex. EMBO J 14(14):3528–3539

    Article  CAS  Google Scholar 

  40. Schmutz I, Ripperger JA et al (2010) The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors. Genes Dev 24(4):345–357

    Article  CAS  Google Scholar 

  41. Bae K, ** X et al (2001) Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian clock. Neuron 30(2):525–536

    Article  CAS  Google Scholar 

  42. Pendergast JS, Niswender KD et al (2012) Tissue-specific function of Period3 in circadian rhythmicity. PLoS One. 7(1):e30254

    Article  CAS  Google Scholar 

  43. Ramanathan C, Xu H et al (2014) Cell type-specific functions of period genes revealed by novel adipocyte and hepatocyte circadian clock models. PLoS Genet 10(4):e1004244

    Article  CAS  Google Scholar 

  44. Englund A, Kovanen L et al (2009) NPAS2 and PER2 are linked to risk factors of the metabolic syndrome. J Circadian Rhythms 7:5

    Article  CAS  Google Scholar 

  45. van der Horst GT, Muijtjens M et al (1999) Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms. Nature 398(6728):627–630

    Article  Google Scholar 

  46. Vitaterna MH, Selby CP et al (1999) Differential regulation of mammalian period genes and circadian rhythmicity by cryptochromes 1 and 2. Proc Natl Acad Sci U S A 96(21):12114–12119

    Article  CAS  Google Scholar 

  47. Shirogane T, ** J et al (2005) SCFbeta-TRCP controls clock-dependent transcription via casein kinase 1-dependent degradation of the mammalian period-1 (Per1) protein. J Biol Chem 280(29):26863–26872

    Article  CAS  Google Scholar 

  48. Eide EJ, Woolf MF et al (2005) Control of mammalian circadian rhythm by CKIepsilon-regulated proteasome-mediated PER2 degradation. Mol Cell Biol 25(7):2795–2807

    Article  CAS  Google Scholar 

  49. Lamia KA, Sachdeva UM et al (2009) AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation. Science 326(5951):437–440

    Article  CAS  Google Scholar 

  50. Godinho SI, Maywood ES et al (2007) The after-hours mutant reveals a role for Fbxl3 in determining mammalian circadian period. Science 316(5826):897–900

    Article  CAS  Google Scholar 

  51. Yoo SH, Mohawk JA et al (2013) Competing E3 ubiquitin ligases govern circadian periodicity by degradation of CRY in nucleus and cytoplasm. Cell 152:109–105

    Article  CAS  Google Scholar 

  52. Miyajima N, Horiuchi R et al (1989) Two erbA homologs encoding proteins with different T3 binding capacities are transcribed from opposite DNA strands of the same genetic locus. Cell 57:31–39

    Article  CAS  Google Scholar 

  53. Yin L, Wu N et al (2010) Nuclear receptor Rev-erbalpha: a heme receptor that coordinates circadian rhythm and metabolism. Nucl Recept Signal 8:e001

    Article  CAS  Google Scholar 

  54. Everett LJ, Lazar MA (2014) Nuclear receptor Rev-erbα: up, down, and all around. Trends Endocrinol Metab 25:586–592

    Article  CAS  Google Scholar 

  55. Kojetin DJ, Burris TP (2014) REV-ERB and ROR nuclear receptors as drug targets. Nat Rev Drug Discov 13:197–216

    Article  CAS  Google Scholar 

  56. Alenghat T, Meyers K et al (2008) Nuclear receptor corepressor and histone deacetylase 3 govern circadian metabolic physiology. Nature 456:997–1000

    Article  CAS  Google Scholar 

  57. Papazyan R, Zhang Y et al (2016) Genetic and epigenomic mechanisms of mammalian circadian transcription. Nat Struct Mol Biol 23:1045–1052

    Article  CAS  Google Scholar 

  58. Chen M, Guan B et al (2019) The molecular mechanism regulating diurnal rhythm of flavin-containing monooxygenase 5 in mouse liver. Drug Metab Dispos 47:1333–1342

    Article  CAS  Google Scholar 

  59. Yu X, Rollins D et al (2013) TH17 cell differentiation is regulated by the circadian clock. Science 342:727–730

    Article  CAS  Google Scholar 

  60. Zhang Y, Fang B et al (2015) Discrete functions of nuclear receptor Rev-erbα couple metabolism to the clock. Science 348:1488–1492

    Article  CAS  Google Scholar 

  61. Caratti G, Iqbal M et al (2018) REVERB a couples the circadian clock to hepatic glucocorticoid action. J Clin Invest 128:4454–4471

    Article  Google Scholar 

  62. Welch RD, al GC (2017) Rev-Erb co-regulates muscle regeneration via tethered interaction with the NF-Y cistrome. Mol Metab 6:703–714

    Article  CAS  Google Scholar 

  63. Cho H, Zhao X et al (2012) Regulation of circadian behaviour and metabolism by REV-ERB-α and REV-ERB-β. Nature 485:123–127

    Article  CAS  Google Scholar 

  64. Kim J, Jang S et al (2017) Implications of circadian rhythm in dopamine and mood regulation. Mol Cells 40(7):450–456

    CAS  Google Scholar 

  65. Breen DP, Vuono R et al (2014) Sleep and circadian rhythm regulation in early Parkinson disease. JAMA Neurol 71(5):589–595

    Article  Google Scholar 

  66. Solt LA, Wang Y et al (2012) Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature 485:62–68

    Article  CAS  Google Scholar 

  67. Becker-André M, André E et al (1993) Identification of nuclear receptor mRNAs by RT-PCR amplification of conserved zinc-finger motif sequences. Biochem Biophys Res Commun 194(3):1371–1379

    Article  Google Scholar 

  68. Giguère V, Tini M et al (1994) Isoform-specific amino-terminal domains dictate DNA-binding properties of ROR alpha, a novel family of orphan hormone nuclear receptors. Genes Dev 8(5):538–553

    Article  Google Scholar 

  69. Carlberg C, Hooft van Huijsduijnen R et al (1994) RZRs, a new family of retinoid-related orphan receptors that function as both monomers and homodimers. Mol Endocrinol 8(6):757–770

    CAS  Google Scholar 

  70. André E, Conquet F et al (1998) Disruption of retinoid-related orphan receptor beta changes circadian behavior, causes retinal degeneration and leads to vacillans phenotype in mice. EMBO J 17(14):3867–3877

    Article  Google Scholar 

  71. Banerjee D, Zhao L et al (2016) Small molecule mediated inhibition of RORγ-dependent gene expression and autoimmune disease pathology in vivo. Immunology 147(4):399–413

    Article  CAS  Google Scholar 

  72. Liu AC, Tran HG et al (2008) Redundant function of REV-ERBalpha and beta and non-essential role for Bmal1 cycling in transcriptional regulation of intracellular circadian rhythms. PLoS Genet 4(2):e1000023

    Article  CAS  Google Scholar 

  73. Steinmayr M, André E et al (1998) staggerer phenotype in retinoid-related orphan receptor alpha-deficient mice. Proc Natl Acad Sci U S A 95(7):3960–3965

    Article  CAS  Google Scholar 

  74. Hunger SP, Li S et al (1996) The proto-oncogene HLF and the related basic leucine zipper protein TEF display highly similar DNA-binding and transcriptional regulatory properties. Blood 87:4607–4617

    Article  CAS  Google Scholar 

  75. Ripperger JA, Shearman LP et al (2000) CLOCK, an essential pacemaker component, controls expression of the circadian transcription factor DBP. Genes Dev 14:679–689

    CAS  Google Scholar 

  76. Gachon F, Olela FF et al (2006) The circadian PAR-domain basic leucine zipper transcription factors DBP, TEF, and HLF modulate basal and inducible xenobiotic detoxification. Cell Metab 4(1):25–36

    Article  CAS  Google Scholar 

  77. Falvey E, Marcacci L et al (1996) DNA-binding specificity of PAR and C/EBP leucine zipper proteins: a single amino acid substitution in the C/EBP DNA-binding domain confers PAR-like specificity to C/EBP. Biol Chem 377:797–809

    CAS  Google Scholar 

  78. Lavery DJ, Lopez-Molina L et al (1999) Circadian expression of the steroid 15 alpha-hydroxylase (Cyp2a4) and coumarin 7-hydroxylase (Cyp2a5) genes in mouse liver is regulated by the PAR leucine zipper transcription factor DBP. Mol Cell Biol 19(10):6488–6499

    Article  CAS  Google Scholar 

  79. Cowell IG, Hurst HC (1994) Transcriptional repression by the human bZIP factor E4BP4: definition of a minimal repression domain. Nucleic Acids Res 22(1):59–65

    Article  CAS  Google Scholar 

  80. Cowell IG, Hurst HC (1996) Protein-protein interaction between the transcriptional repressor E4BP4 and the TBP-binding protein Dr1. Nucleic Acids Res 24:3607–3613

    Article  CAS  Google Scholar 

  81. Zhang W, Zhang J et al (1995) Molecular cloning and characterization of NF-IL3A, a transcriptional activator of the human interleukin-3 promoter. Mol Cell Biol 15:6055–6063

    Article  CAS  Google Scholar 

  82. Cowell IG, Skinner A et al (1992) Transcriptional repression by a novel member of the bZIP family of transcription factors. Mol Cell Biol 12:3070–3077

    Article  CAS  Google Scholar 

  83. Tong Y, Zeng P et al (2019) The transcription factor E4bp4 regulates the expression and activity of Cyp3a11 in mice. Biochem Pharmacol 163:215–224

    Article  CAS  Google Scholar 

  84. Ohno T, Onishi Y et al (2007) The negative transcription factor E4BP4 is associated with circadian clock protein PERIOD2. Biochem Biophys Res Commun 354(4):1010–1015

    Article  CAS  Google Scholar 

  85. Suwazono Y, Dochi M et al (2009) Shiftwork and impaired glucose metabolism: a 14-year cohort study on 7104 male workers. Chronobiol Int 26(5):926–941

    Article  CAS  Google Scholar 

  86. Parsons MJ, Moffitt TE et al (2015) Social jetlag, obesity and metabolic disorder: investigation in a cohort study. Int J Obes 39(5):842–848

    Article  CAS  Google Scholar 

  87. Nedeltcheva AV, Scheer FA (2014) Metabolic effects of sleep disruption, links to obesity and diabetes. Curr Opin Endocrinol Diab Obes 21:293–298

    Article  Google Scholar 

  88. Maury E (2019) Off the clock: from circadian disruption to metabolic disease. Int J Mol Sci 20(7):1597

    Article  CAS  Google Scholar 

  89. Albrecht U, Ripperger JA (2018) Circadian clocks and sleep: impact of rhythmic metabolism and waste clearance on the brain. Trends Neurosci 41(10):677–688

    Article  CAS  Google Scholar 

  90. Scott EM, Carter AM et al (2008) Association between polymorphisms in the clock gene, obesity and the metabolic syndrome in man. Int J Obes 32:658–662

    Article  CAS  Google Scholar 

  91. Woon PY, Kaisaki PJ et al (2007) Aryl hydrocarbon receptor nuclear translocator-like (BMAL1) is associated with susceptibility to hypertension and type 2 diabetes. Proc Natl Acad Sci USA 104:14412–14417

    Article  CAS  Google Scholar 

  92. Sadacca LA, Lamia KA et al (2011) An intrinsic circadian clock of the pancreas is required for normal insulin release and glucose homeostasis in mice. Diabetologia 54(1):120–124

    Article  CAS  Google Scholar 

  93. Yang S, Liu A et al (2009) The role of mPer2 clock gene in glucocorticoid and feeding rhythms. Endocrinology 150:2153–2160

    Article  CAS  Google Scholar 

  94. Chaix A, Lin T et al (2019) Timerestricted feeding prevents obesity and metabolic syndrome in mice lacking a circadian clock. Cell Metab 29:303–319

    Article  CAS  Google Scholar 

  95. S-q S, Ansari TS et al (2013) Circadian disruption leads to insulin resistance and obesity. Curr Biol 23:372–381

    Article  CAS  Google Scholar 

  96. Turek FW et al (2005) Obesity and metabolic syndrome in circadian clock mutant mice. Science 308(5724):1043–1045

    Article  CAS  Google Scholar 

  97. Eckel-Mahan K, Sassone-Corsi P (2009) Metabolism control by the circadian clock and vice versa. Nat Struct Mol Biol 16(5):462–467

    Article  CAS  Google Scholar 

  98. Oren F (2012) Circadian rhythms and obesity in mammals. ISRN Obes 18(2012):437198

    Google Scholar 

  99. Kalsbeek A, Yi CX et al (2010) The hypothalamic clock and its control of glucose homeostasis. Trends Endocrinol Metab 21(7):402–410

    Article  CAS  Google Scholar 

  100. Boden G, Chen G et al (1999) Disruption of circadian insulin secretion is associated with reduced glucose uptake in first-degree relatives of patients with type 2 diabetes. Diabetes 48(11):2182–2188

    Article  CAS  Google Scholar 

  101. Yang G, Jia Z et al (2012) Systemic PPARγ deletion impairs circadian rhythms of behavior and metabolism. PLoS One 7:e38117

    Article  CAS  Google Scholar 

  102. Kollias GE et al (2009) Diurnal variation of endothelial function and arterial stiffness in hypertension. J Hum Hypertens 23:597

    Article  CAS  Google Scholar 

  103. Degaute JP, van de Borne P et al (1991) Quantitative analysis of the 24-hour blood pressure and heart rate patterns in young men. Hypertension 18(2):199–210

    Article  CAS  Google Scholar 

  104. Vyas MV, Garg AX et al (2012) Shift work and vascular events: systematic review and meta-analysis. BMJ 345:e4800

    Article  Google Scholar 

  105. Lo SH, Lin LY et al (2010) Working the night shift causes increased vascular stress and delayed recovery in young women. Chronobiol Int 27(7):1454–1468

    Article  Google Scholar 

  106. Bray MS, Shaw CA et al (2008) Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression. Am J Physiol Heart Circ Physiol 294(2):H1036–H1047

    Article  CAS  Google Scholar 

  107. Curtis AM, Cheng Y et al (2007) Circadian variation of blood pressure and the vascular response to asynchronous stress. Proc Natl Acad Sci U S A 104(9):3450–3455

    Article  CAS  Google Scholar 

  108. Viswambharan H, Carvas JM et al (2007) Mutation of the circadian clock gene Per2 alters vascular endothelial function. Circulation 115(16):2188–2195

    Article  CAS  Google Scholar 

  109. Wang Q, Maillard M et al (2010) Cardiac hypertrophy, low blood pressure, and low aldosterone levels in mice devoid of the three circadian PAR bZip transcription factors DBP, HLF, and TEF. Am J Physiol Regul Integr Comp Physiol 299(4):R1013–R1019

    Article  CAS  Google Scholar 

  110. De Scalzi M, De Leonardis V et al (1984) Heart rate and premature beats: a chronobiologic study. Giornale Italiano di Cardiologia 14:465–470

    Google Scholar 

  111. Harshfield GA, Barbeau P et al (2000) Racial differences in the influence of body size on ambulatory blood pressure in youths. Blood Press Monit 5:59–63

    CAS  Google Scholar 

  112. Kario K, Matsuo T et al (1996) Relation between nocturnal fall of blood pressure and silent cerebrovascular damage in elderly hypertensives: advanced silent cerebrovascular damage in extreme-dippers. Hypertension 27:130–135

    Article  CAS  Google Scholar 

  113. Furlan R, Guzzetti S et al (1990) Continuous 24-hour assessment of the neural regulation of systemic arterial pressure and RR variabilities in ambulant subjects. Circulation 81(2):537–547

    Article  CAS  Google Scholar 

  114. Andrews NP, Gralnick HR et al (1996) Mechanisms underlying the morning increase in platelet aggregation: a flow cytometry study. J Am Coll Cardiol 28:1789–1795

    Article  CAS  Google Scholar 

  115. Goldstein S, Zoble RG et al (1996) Relation of circadian ventricular ectopic activity to cardiac mortality. CAST Investigators. Am J Cardiol 78:881–885

    Article  CAS  Google Scholar 

  116. Muller JE, Ludmer PL et al (1987) Circadian variation in the frequency of sudden cardiac death. Circulation 75:131–138

    Article  CAS  Google Scholar 

  117. Willich SN, Linderer T et al (1989) Increased morning incidence of myocardial infarction in the ISAM study: absence with prior beta-adrenergic blockade. Circulation 80:853–858

    Article  CAS  Google Scholar 

  118. Elliott WJ (1998) Circadian variation in the timing of stroke onset: a meta-analysis. Stroke 29:992–996

    Article  CAS  Google Scholar 

  119. Rocco MB, Barry J et al (1987) Circadian variation of transient myocardial ischemia in patients with coronary artery disease. Circulation 75:395–400

    Article  CAS  Google Scholar 

  120. Haus E, Smolensky MH (1999) Biologic rhythms in the immune system. Chronobiol Int 16(5):581–622

    Article  CAS  Google Scholar 

  121. Labrecque N, Cermakian N (2015) Circadian clocks in the immune system. J Biol Rhythms 30(4):277–290

    Article  CAS  Google Scholar 

  122. Paganelli R, Petrarca C et al (2018) Biological clocks: their relevance to immune-allergic diseases. Clin Mol Allergy 16:1

    Article  CAS  Google Scholar 

  123. Hergenhan S, Holtkamp S et al (2020) Molecular interactions between components of the circadian clock and the immune system. J Mol Biol 432(12):3700–3713

    Article  CAS  Google Scholar 

  124. Gibbs JE, Ray DW (2013) The role of the circadian clock in rheumatoid arthritis. Arthritis Res Ther 15:205

    Article  Google Scholar 

  125. Durrington HJ, Farrow SN (2014) The circadian clock and asthma. Thorax 69:90–92

    Article  Google Scholar 

  126. Sutherland ER (2005) Nocturnal asthma. J Allergy Clin Immunol 116:1179–1186

    Article  Google Scholar 

  127. Reinberg A, Gervais P et al (1988) Circadian and circannual rhythms of allergic rhinitis: an epidemiologic study involving chronobiologic methods. J Allergy Clin Immunol 81(1):51–62

    Article  CAS  Google Scholar 

  128. Kondratov RV, Kondratova AA et al (2006) rly aging and age-related pathologies in mice deficient in BMAL1, the core component of the circadian clock. Genes Dev 20(14):1868–1873

    Article  CAS  Google Scholar 

  129. Antoch MP, Gorbacheva VY et al (2008) Disruption of the circadian clock due to the clock mutation has discrete effects on aging and carcinogenesis. Cell Cycle 7(9):1197–1204

    Article  CAS  Google Scholar 

  130. Myers BL, Badia P (1995) Changes in circadian rhythms and sleep quality with aging: mechanisms and interventions. Neurosci Biobehav Rev 19(4):553–571

    Article  CAS  Google Scholar 

  131. Swaab DF, Fliers E et al (1985) The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia. Brain Res 342(1):37–44

    Article  CAS  Google Scholar 

  132. Froy O (2011) Circadian rhythms, aging, and life span in mammals. Physiology 26(4):225–235

    Article  CAS  Google Scholar 

  133. Biello SM (2009) Circadian clock resetting in the mouse changes with age. Age 31(4):293–303

    Article  Google Scholar 

  134. Pardo B, Gómez-González B et al (2009) DNA repair in mammalian cells. Cell Mol Life Sci 66:1039–1056

    Article  CAS  Google Scholar 

  135. Robertson A, Klungland A et al (2009) DNA repair in mammalian cells. Cell Mol Life Sci 66:981–993

    Article  CAS  Google Scholar 

  136. Flynn-Evans EE, Mucci L et al (2013) Shiftwork and prostate-specific antigen in the National Health and nutrition examination survey. J Natl Cancer Inst 105(17):1292–1297

    Article  CAS  Google Scholar 

  137. Stevens RG (2005) Circadian disruption and breast cancer: from melatonin to clock genes. Epidemiology 16:254–258

    Article  Google Scholar 

  138. Marinac CR, Natarajan L et al (2015) Prolonged nightly fasting and breast cancer risk: findings from NHANES (2009–2010). Cancer Epidemiol Biomarkers Prev 24(5):783–789

    Article  CAS  Google Scholar 

  139. Kogevinas M, Espinosa A et al (2018) Effect of mistimed eating patterns on breast and prostate cancer risk (MCC-Spain Study). Int J Cancer 143:2380–2389

    Article  CAS  Google Scholar 

  140. Mormont MC, Waterhouse J et al (2000) Marked 24-h rest/activity rhythms are associated with better quality of life, better response, and longer survival in patients with metastatic colorectal cancer and good performance status. Clin Cancer Res 6:3038–3045

    CAS  Google Scholar 

  141. Innominato PF, Komarzynski S et al (2018) Circadian rest–activity rhythm as an objective biomarker of patient-reported outcomes in patients with advanced cancer. Cancer Med 7:4396–4405

    Article  Google Scholar 

  142. Lee S, Donehower LA et al (2010) Disrupting circadian homeostasis of sympathetic signaling promotes tumor development in mice. PLoS One 5:e10995

    Article  CAS  Google Scholar 

  143. Wood PA, Yang X et al (2008) Period 2 mutation accelerates ApcMin/+tumorigenesis. Mol Cancer Res 6:1786–1793

    Article  CAS  Google Scholar 

  144. Gu X, **ng L et al (2012) The circadian mutation PER2(S662G) is linked to cell cycle progression and tumorigenesis. Cell Death Differ 19:397–405

    Article  CAS  Google Scholar 

  145. Gery S, Komatsu N et al (2005) The circadian gene Per1 plays an important role in cell growth and DNA damage control in human cancer cells. Mol Cell 22:375–382

    Article  CAS  Google Scholar 

  146. Abbas T, Dutta A (2009) p21 in cancer: intricate networks and multiple activities. Nat Rev Cancer 9:400–414

    Article  CAS  Google Scholar 

  147. Kang THH, Leem SHH (2014) Modulation of ATR-mediated DNA damage checkpoint response by cryptochrome 1. Nucleic Acids Res 42:4427–4434

    Article  CAS  Google Scholar 

  148. Kondratov RV, Antoch MP (2007) Circadian proteins in the regulation of cell cycle and genotoxic stress responses. Trends Cell Biol 17:311–317

    Article  CAS  Google Scholar 

  149. Papagiannakopoulos T, Bauer MR et al (2016) Circadian rhythm disruption promotes lung tumorigenesis. Cell Metab 24(2):324–331

    Article  CAS  Google Scholar 

  150. Li HX, Yang K et al (2016) Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae 38(2):155–163

    CAS  Google Scholar 

  151. Liu Y, Sato F et al (2010) Anti-apoptotic effect of the basic helix-loop-helix (bHLH) transcription factor DEC2 in human breast cancer cells. Genes Cells 15:315–325

    Article  CAS  Google Scholar 

  152. Kang T-HH, Reardon JT et al (2011) Regulation of nucleotide excision repair activity by transcriptional and post-transcriptional control of the XPA protein. Nucleic Acids Res 39:3176–3187

    Article  CAS  Google Scholar 

  153. Kang T-HH, Lindsey-Boltz LA et al (2010) Circadian control of XPA and excision repair of cisplatin-DNA damage by cryptochrome and HERC2 ubiquitin ligase. Proc Natl Acad Sci U S A 107:4890–4895

    Article  CAS  Google Scholar 

  154. Barnes JW, Tischkau SA et al (2003) Requirement of mammalian timeless for circadian rhythmicity. Science 302:439–442

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2020 The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Zhao, M., Lu, D., Chen, M., Wu, B. (2020). Introduction to Mammalian Circadian Clock System. In: Wu, B., Lu, D., Dong, D. (eds) Circadian Pharmacokinetics. Springer, Singapore. https://doi.org/10.1007/978-981-15-8807-5_1

Download citation

Publish with us

Policies and ethics

Navigation