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The Journal of Physiological Sciences

, Volume 68, Issue 4, pp 377–385 | Cite as

The central clock controls the daily rhythm of Aqp5 expression in salivary glands

  • Hitoshi Uchida
  • Takahiro J. Nakamura
  • Nana N. Takasu
  • Aya Obana-Koshino
  • Hitomi Ono
  • Takeshi Todo
  • Takayoshi Sakai
  • Wataru NakamuraEmail author
Original Paper

Abstract

Salivary secretion displays day–night variations that are controlled by the circadian clock. The central clock in the suprachiasmatic nucleus (SCN) regulates daily physiological rhythms by prompting peripheral oscillators to adjust to changing environments. Aquaporin 5 (Aqp5) is known to play a key role in salivary secretion, but the association between Aqp5 and the circadian rhythm is poorly understood. The aim of our study was to evaluate whether Aqp5 expression in submandibular glands (SMGs) is driven by the central clock in the SCN or by autonomous oscillations. We observed circadian oscillations in the activity of period circadian protein homolog 2 and luciferase fusion protein (PER2::LUC) in cultured SMGs with periodicity depending on core clock genes. A daily rhythm was detected in the expression profiles of Aqp5 in SMGs in vivo. In cultured SMGs ex vivo, clock genes showed distinct circadian rhythms, whereas Aqp5 expression did not. These data indicate that daily Aqp5 expression in the mouse SMG is driven by the central clock in the SCN.

Keywords

Circadian rhythm Salivary gland Suprachiasmatic nucleus Aquaporin 5 Period 2 

Notes

Author contributions

H.U. and W.N. designed the research; H.U., T.J.N., N.N.T., and W.N. performed the research; A.O.K., H.O., T.T., and T.S. contributed new reagents/analytic tools; H.U., T.J.N., N.N.T., and W.N. analyzed the data; H.U., T.J.N., N.N.T., and W.N. wrote the paper.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

This work was supported by JSPS KAKENHI grant numbers 26462809, 26860160, 26861780. N.N.T. is a research fellow of the Japan Society for the Promotion of Science.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The Protocol was approved by the Animal Care and Use Committee at Osaka University.

References

  1. 1.
    Brosky ME (2007) The role of saliva in oral health: strategies for prevention and management of xerostomia. J Support Oncol 5:215–225PubMedGoogle Scholar
  2. 2.
    Rudney JD (1995) Does variability in salivary protein concentrations influence oral microbial ecology and oral health? Crit Rev Oral Biol Med 6:343–367CrossRefGoogle Scholar
  3. 3.
    Cohen S (1962) Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. J Biol Chem 237:1555–1562PubMedGoogle Scholar
  4. 4.
    Levine MJ (1993) Development of artificial salivas. Crit Rev Oral Biol Med 4:279–286CrossRefGoogle Scholar
  5. 5.
    Schneyer LH, Levin LK (1955) Rate of secretion by individual salivary gland pairs of man under conditions of reduced exogenous stimulation. J Appl Physiol 7:508–512CrossRefGoogle Scholar
  6. 6.
    Abe K, Dawes C (1978) The effects of electrical and pharmacological stimulation on the types of proteins secreted by rat parotid and submandibular glands. Arch Oral Biol 23:367–372CrossRefGoogle Scholar
  7. 7.
    Garrett JR, Suleiman AM, Anderson LC, Proctor GB (1991) Secretory responses in granular ducts and acini of submandibular glands in vivo to parasympathetic or sympathetic nerve stimulation in rats. Cell Tissue Res 264:117–126CrossRefGoogle Scholar
  8. 8.
    Garrett JR, Thulin A (1975) Changes in parotid acinar cells accompanying salivary secretion in rats on sympathetic or parasympathetic nerve stimulation. Cell Tissue Res 159:179–193CrossRefGoogle Scholar
  9. 9.
    Dawes C (1972) Circadian rhythms in human salivary flow rate and composition. J Physiol 220:529–545CrossRefGoogle Scholar
  10. 10.
    Siminoski K, Bernanke J, Murphy RA (1993) Nerve growth factor and epidermal growth factor in mouse submandibular glands: identical diurnal changes and rates of secretagogue-induced synthesis. Endocrinology 132:2031–2037CrossRefGoogle Scholar
  11. 11.
    Basso A, Piantanelli L (2002) Influence of age on circadian rhythms of adrenoceptors in brain cortex, heart and submandibular glands of BALB/c mice: when circadian studies are not only useful but necessary. Exp Gerontol 37:1441–1450CrossRefGoogle Scholar
  12. 12.
    Agre P, King LS, Yasui M, Guggino WB, Ottersen OP, Fujiyoshi Y, Engel A, Nielsen S (2002) Aquaporin water channels–from atomic structure to clinical medicine. J Physiol 542:3–16CrossRefGoogle Scholar
  13. 13.
    Castle NA (2005) Aquaporins as targets for drug discovery. Drug Discov Today 10:485–493CrossRefGoogle Scholar
  14. 14.
    Verkman AS (2005) More than just water channels: unexpected cellular roles of aquaporins. J Cell Sci 118:3225–3232CrossRefGoogle Scholar
  15. 15.
    Delporte C, Steinfeld S (2006) Distribution and roles of aquaporins in salivary glands. Biochim Biophys Acta 1758:1061–1070CrossRefGoogle Scholar
  16. 16.
    Ma T, Song Y, Gillespie A, Carlson EJ, Epstein CJ, Verkman AS (1999) Defective secretion of saliva in transgenic mice lacking aquaporin-5 water channels. J Biol Chem 274:20071–20074CrossRefGoogle Scholar
  17. 17.
    Yang B, Song Y, Zhao D, Verkman AS (2005) Phenotype analysis of aquaporin-8 null mice. Am J Physiol Cell Physiol 288:C1161–C1170CrossRefGoogle Scholar
  18. 18.
    Nakamura TJ, Takasu NN, Nakamura W (2016) The suprachiasmatic nucleus: age-related decline in biological rhythms. J Physiol Sci 66:367–374CrossRefGoogle Scholar
  19. 19.
    Abe M, Herzog ED, Yamazaki S, Straume M, Tei H, Sakaki Y, Menaker M, Block GD (2002) Circadian rhythms in isolated brain regions. J Neurosci 22:350–356CrossRefGoogle Scholar
  20. 20.
    Uchida H, Nakamura TJ, Takasu NN, Todo T, Sakai T, Nakamura W (2016) Cryptochrome-dependent circadian periods in the arcuate nucleus. Neurosci Lett 610:123–128CrossRefGoogle Scholar
  21. 21.
    Tahara Y, Kuroda H, Saito K, Nakajima Y, Kubo Y, Ohnishi N, Seo Y, Otsuka M, Fuse Y, Ohura Y et al (2012) In vivo monitoring of peripheral circadian clocks in the mouse. Curr Biol 22:1029–1034CrossRefGoogle Scholar
  22. 22.
    Yamazaki S, Numano R, Abe M, Hida A, Takahashi R, Ueda M, Block GD, Sakaki Y, Menaker M, Tei H (2000) Resetting central and peripheral circadian oscillators in transgenic rats. Science 288:682–685CrossRefGoogle Scholar
  23. 23.
    Yoo SH, Yamazaki S, Lowrey PL, Shimomura K, Ko CH, Buhr ED, Siepka SM, Hong HK, Oh WJ, Yoo OJ et al (2004) PERIOD2:LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues. Proc Natl Acad Sci USA 101:5339–5346CrossRefGoogle Scholar
  24. 24.
    Reppert SM, Weaver DR (2002) Coordination of circadian timing in mammals. Nature 418:935–941CrossRefGoogle Scholar
  25. 25.
    Inouye ST, Kawamura H (1979) Persistence of circadian rhythmicity in a mammalian hypothalamic “island” containing the suprachiasmatic nucleus. Proc Natl Acad Sci USA 76:5962–5966CrossRefGoogle Scholar
  26. 26.
    Meyer-Bernstein EL, Jetton AE, Matsumoto SI, Markuns JF, Lehman MN, Bittman EL (1999) Effects of suprachiasmatic transplants on circadian rhythms of neuroendocrine function in golden hamsters. Endocrinology 140:207–218CrossRefGoogle Scholar
  27. 27.
    Schwartz WJ, Gross RA, Morton MT (1987) The suprachiasmatic nuclei contain a tetrodotoxin-resistant circadian pacemaker. Proc Natl Acad Sci USA 84:1694–1698CrossRefGoogle Scholar
  28. 28.
    Vitaterna MH, Selby CP, Todo T, Niwa H, Thompson C, Fruechte EM, Hitomi K, Thresher RJ, Ishikawa T, Miyazaki J et al (1999) Differential regulation of mammalian period genes and circadian rhythmicity by cryptochromes 1 and 2. Proc Natl Acad Sci USA 96:12114–12119CrossRefGoogle Scholar
  29. 29.
    Furukawa M, Kawamoto T, Noshiro M, Honda KK, Sakai M, Fujimoto K, Honma S, Honma K, Hamada T, Kato Y (2005) Clock gene expression in the submandibular glands. J Dent Res 84:1193–1197CrossRefGoogle Scholar
  30. 30.
    Zheng L, Seon YJ, McHugh J, Papagerakis S, Papagerakis P (2012) Clock genes show circadian rhythms in salivary glands. J Dent Res 91:783–788CrossRefGoogle Scholar
  31. 31.
    Nakamura TJ, Nakamura W, Tokuda IT, Ishikawa T, Kudo T, Colwell CS, Block GD (2015) Age-related changes in the circadian system unmasked by constant conditions. eNeuro 2(4). doi: 10.1523/ENEURO.0064-15.2015
  32. 32.
    Sakai T, Larsen M, Yamada KM (2003) Fibronectin requirement in branching morphogenesis. Nature 423:876–881CrossRefGoogle Scholar
  33. 33.
    Nakamura W, Yamazaki S, Takasu NN, Mishima K, Block GD (2005) Differential response of Period 1 expression within the suprachiasmatic nucleus. J Neurosci 25:5481–5487CrossRefGoogle Scholar
  34. 34.
    Ueyama T, Krout KE, Nguyen XV, Karpitskiy V, Kollert A, Mettenleiter TC, Loewy AD (1999) Suprachiasmatic nucleus: a central autonomic clock. Nat Neurosci 2:1051–1053CrossRefGoogle Scholar
  35. 35.
    Ungar F, Halberg F (1962) Circadian rhythm in the in vitro response of mouse adrenal to adrenocorticotropic hormone. Science 137:1058–1060CrossRefGoogle Scholar
  36. 36.
    Tosini G, Menaker M (1996) Circadian rhythms in cultured mammalian retina. Science 272:419–421CrossRefGoogle Scholar
  37. 37.
    Doi M, Takahashi Y, Komatsu R, Yamazaki F, Yamada H, Haraguchi S, Emoto N, Okuno Y, Tsujimoto G, Kanematsu A et al (2010) Salt-sensitive hypertension in circadian clock-deficient Cry-null mice involves dysregulated adrenal Hsd3b6. Nat Med 16:67–74CrossRefGoogle Scholar
  38. 38.
    Evans JA, Pan H, Liu AC, Welsh DK (2012) Cry1−/− circadian rhythmicity depends on SCN intercellular coupling. J Biol Rhythms 27:443–452CrossRefGoogle Scholar
  39. 39.
    Gresz V, Kwon TH, Hurley PT, Varga G, Zelles T, Nielsen S, Case RM, Steward MC (2001) Identification and localization of aquaporin water channels in human salivary glands. Am J Physiol Gastrointest Liver Physiol 281:G247–G254CrossRefGoogle Scholar
  40. 40.
    Matsuzaki T, Ablimit A, Suzuki T, Aoki T, Hagiwara H, Takata K (2006) Changes of aquaporin 5-distribution during release and reaccumulation of secretory granules in isoproterenol-treated mouse parotid gland. J Electron Microsc (Tokyo) 55:183–189CrossRefGoogle Scholar
  41. 41.
    Ueda HR, Hayashi S, Chen W, Sano M, Machida M, Shigeyoshi Y, Iino M, Hashimoto S (2005) System-level identification of transcriptional circuits underlying mammalian circadian clocks. Nat Genet 37:187–192CrossRefGoogle Scholar
  42. 42.
    Krane CM, Melvin JE, Nguyen HV, Richardson L, Towne JE, Doetschman T, Menon AG (2001) Salivary acinar cells from aquaporin 5-deficient mice have decreased membrane water permeability and altered cell volume regulation. J Biol Chem 276:23413–23420CrossRefGoogle Scholar
  43. 43.
    Koike N, Yoo SH, Huang HC, Kumar V, Lee C, Kim TK, Takahashi JS (2012) Transcriptional architecture and chromatin landscape of the core circadian clock in mammals. Science 338:349–354CrossRefGoogle Scholar
  44. 44.
    Vujovic N, Davidson AJ, Menaker M (2008) Sympathetic input modulates, but does not determine, phase of peripheral circadian oscillators. Am J Physiol Regul Integr Comp Physiol 295:R355–R360CrossRefGoogle Scholar
  45. 45.
    Bnado H, Nishio T, van der Horst GTJ, Masubuchi S, Hisa Y, Okamura H (2007) Vagal regulation of respiratory clocks in mice. J Neurosci 27:4359–4365CrossRefGoogle Scholar

Copyright information

© The Physiological Society of Japan and Springer Japan 2017

Authors and Affiliations

  • Hitoshi Uchida
    • 1
    • 2
  • Takahiro J. Nakamura
    • 3
    • 4
  • Nana N. Takasu
    • 1
  • Aya Obana-Koshino
    • 2
  • Hitomi Ono
    • 2
  • Takeshi Todo
    • 5
  • Takayoshi Sakai
    • 2
  • Wataru Nakamura
    • 1
    Email author
  1. 1.Department of Oral-Chrono PhysiologyNagasaki University Graduate School of Biomedical SciencesNagasakiJapan
  2. 2.Department of Oral-Facial Disorders, Graduate School of DentistryOsaka UniversitySuitaJapan
  3. 3.Department of Life Sciences, School of AgricultureMeiji UniversityKawasakiJapan
  4. 4.Faculty of Pharmaceutical SciencesTeikyo Heisei UniversityTokyoJapan
  5. 5.Department of Radiation Biology and Medical Genetics, Graduate School of MedicineOsaka UniversitySuitaJapan

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