생명과학회지 (Journal of Life Science)

  • 제23권8호
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  • Pages.1064-1072
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  • 2013
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  • 1225-9918(pISSN)
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  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
권호 표지
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주기적 리듬 조절에 의한 멜라토닌 생산과 생리적 기능의 중요성

Rhythmic Control and Physiological Functional Significance of Melatonin Production in Circadian Rhythm

  • 김민균 (부산대학교 의학전문대학원 미생물학 및 면역학 교실) ;
  • 박슬기 (부산대학교 의학전문대학원 미생물학 및 면역학 교실) ;
  • 안순철 (부산대학교 의학전문대학원 미생물학 및 면역학 교실)
  • Kim, Min Gyun (Department of Microbiology and Immunology, Pusan National University School of Medicine) ;
  • Park, Seul Ki (Department of Microbiology and Immunology, Pusan National University School of Medicine) ;
  • Ahn, Soon Cheol (Department of Microbiology and Immunology, Pusan National University School of Medicine)
  • 투고 : 2013.08.22
  • 심사 : 2013.08.27
  • 발행 : 2013.08.30
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초록

일주기 리듬은 모든 살아있는 유기체의 생리현상을 지배하는 호르몬의 변화에 의해서 조절된다. 포유동물에서 송과체의 주된 기능은 시상 하부 시교차 상핵에서 발생되는 일주기 리듬을 주로 어두울 때 증가하는 순환성 멜라토닌의 리듬 신호로 변화시키는 것이다. 송과체는 직접적인 광감도는 없지만, 망막신경절세포로 하부조직을 포함하는 멀티 시냅스 경로를 통하여 빛에 반응한다. 주기적인 리듬 조절은 주위환경의 빛과 멜라토닌 생성의 리듬조절 효소인 arylalkylamine-N-acetyltransferase (AANAT)의 발현과 긴밀한 관계를 통해 이루어진다. 이전 실험에서 AANAT 단백질이 어두울 때의 발현이 전사 조절, 전사 후 조절, 번역 후 조절 메커니즘으로 설명되었다. AANAT 단백질 발현에 관한 분자적 기전은 멜라토닌의 일주기 리듬에 대한 새로운 견해를 제공한다. 광범위한 동물 연구에서 많은 포유류의 계절 리듬을 위한 송과체 멜라토닌은 일주기 리듬의 조절과 수면 조절에 관련이 있는 것으로 알려졌다. 이것은 시차증이나 교대 근무 수면 장애와 같은 일주기 리듬 수면 장애를 치료하는 데 있어서 가치가 있다. 또한 멜라토닌은 다른 영역에도 영향을 미치는데 특히 몸의 생리적 기능을 조절하는데 영향을 미친다. 게다가 정신의학적 질환뿐 만 아니라 생식기 질환, 심혈관 질환, 면역 조절 질환도 이 호르몬에 의해 영향을 받는 것으로 밝혀졌다.

Circadian rhythm is controlled by hormonal oscillations governing the physiology of all living organisms. In mammals, the main function of the pineal gland is to transform the circadian rhythm generated in the hypothalamic suprachiasmatic nucleus into rhythmic signals of circulating melatonin characterized by a largely nocturnal increase that closely reflects the duration of night time. The pineal gland has lost direct photosensitivity, but responds to light via multi-synaptic pathways that include a subset of retinal ganglion cells. Rhythmic control is achieved through a tight coupling between environmental lighting and arylalkylamine-N-acetyltransferase (AANAT) expression, which is the rhythm-controlling enzyme in melatonin synthesis. Previous studies on the nocturnal expression of AANAT protein have described transcriptional, post-transcriptional, and post-translational regulatory mechanisms. Molecular mechanisms for dependent AANAT expression provide novel aspects for melatonin's circadian rhythmicity. Extensive animal research has linked pineal melatonin for the expression of seasonal rhythmicity in many mammalian species to the modulation of circadian rhythms and to sleep regulation. It has value in treating various circadian rhythm disorders, such as jet lag or shift-work sleep disorders. Melatonin, also, in a broad range of effects with a significant regulation influences many of the body's physiological functions. In addition, this hormone is known to influence reproductive, cardiovascular, and immunological regulation as well as psychiatric disorders.

키워드

참고문헌

  1. Arendt, J. 1995. Melatonin and the Mammalian Pineal Gland, pp. 1-14, 1th ed., Chapman & Hall: New York, NY 10119, USA.
  2. Attanasio, A., Borrelli, F. and Gupta, D. 1985. Circadian rhythms in serum melatonin from infancy to adolescence. J Clin Endocrinol Metab 61, 388-390. https://doi.org/10.1210/jcem-61-2-388
  3. Axelrod, J. 1974. The pineal gland: a neurochemical transducer. Science 184, 1341-1348 https://doi.org/10.1126/science.184.4144.1341
  4. Baler, R., Covington, S. and Klein, D. C. 1997. The rat arylalkylamine N-acetyl transferase gene promoter cAMP activation via a cAMP-responsive element–CCAAT complex. J Biol Chem 272, 6979-6985. https://doi.org/10.1074/jbc.272.11.6979
  5. Behar, S., Reicher-Reiss, H., Zion, M., Kaplinsky, E., Mandelzweig, L. and Goldbourt, U. 1993. Circadian variation and possible external trigger of onset of myocardial infraction. Am J Med 94, 395-400. https://doi.org/10.1016/0002-9343(93)90150-N
  6. Berga, S. L., Mortola, J. F. and Yen, S. S. 1988. Amplification of nocturnal melatonin secretion in women with functional hypothalamic amenorrhea. J Clin Endocrinol Metab 66, 242-244. https://doi.org/10.1210/jcem-66-1-242
  7. Binkley, S. 1988. The Pineal: Endocrine and Nonendocrine Function, pp. 134-148, 1th ed., Prentice Hall: Englewood Cliffs, NJ, USA.
  8. Brown, G. M. 1995. Melatonin in psychiatric and sleep disorders: therapeutic implication. CNS Drugs 3, 209-226. https://doi.org/10.2165/00023210-199503030-00006
  9. Bubenik, G. A. 2002. Gastrointestinal melatonin: localization, function, and clinical relevance. Dig Dis Sci 47, 2336-2348. https://doi.org/10.1023/A:1020107915919
  10. Cagnacci, A. 1996. Melatonin in relation to physiology in adult humans. J Pineal Res 21, 200-213. https://doi.org/10.1111/j.1600-079X.1996.tb00287.x
  11. Caroleo, M. C., Frasca, D. and Doria, G. 1992. Melatonin as immunomodulator in immunodeficient mice. Immunopharmacology 23, 81-89. https://doi.org/10.1016/0162-3109(92)90031-7
  12. Carrillo-Vico, A., Calvo, J. R., Lardone, P. J., Garcia-Maurino, S., Reiter, R. J. and Guerrero, J. M. 2004. Evidence of melatonin synthesis by human lymphocytes and its physiological significance: possible role as intracrine, autocrine, and / or paracrine substance. FASEB. J 18, 537-539.
  13. Champier, J., Claustrat, B., Besancon, R., Jouvet, A., Chamba, G. and Fevre-Montange, M. 1997. Evidence for tryptophan hydroxylase and hydroxyindol-O-methyl- transferase mRNAs in human blood platelets. Life Sci 60, 2191-2197. https://doi.org/10.1016/S0024-3205(97)00234-8
  14. Claustrat, B., Brun, J. and Chazot, G. 2005. The basic physiology and pathophysiology of melatonin. Sleep Med Rev 9, 11-24. https://doi.org/10.1016/j.smrv.2004.08.001
  15. Conti, A., Conconi, S., Hertens, E., Skwarlo-Sonta, K., Markowska, M. and Maestroni, J. M. 2000. Evidence for melatonin synthesis in mouse and human bone marrow cells. J Pineal Res 28, 193-202. https://doi.org/10.1034/j.1600-079X.2000.280401.x
  16. Dement, W. C., Miles, L. E. and Carskadon, M. A. 1982. White paper on sleep and aging. J Am Geriatr Soc 30, 25-30.
  17. Fauteck, J. D., Bockmann, J., Bockers, T. M., Wittkowski, W. and Wolf, P. 1995. Melatonin reduces low-Mg2+ epileptiform activity in human temporal slices. Exp Brain Res 107, 321-325.
  18. Ferrier, I. N., Arendt, J., Johnstone, E. C. and Crow, T. J. 1982. Reduced nocturnal melatonin secretion in chronic schizophrenia: relationship to body weight. Clin Endocrinol 17, 181-187. https://doi.org/10.1111/j.1365-2265.1982.tb01577.x
  19. Foulkes, N. S. and Sassone-Corsi, P. 1996. Adaptive inductibility of CREB as transcriptional memory of circadian rhythm. Nature 381, 83-85. https://doi.org/10.1038/381083a0
  20. Gallerani, M., Manfredini, R., Ricci, L., Coccorullo, A., Goldoni, C. and Fersini, C. 1993. Chronobiological aspects of acute cerebrovascular diseases. Acta Neurol Scand 87, 482-487.
  21. Ganguly, S., Coon, S. L. and Klein, D. C. 2002. Control of melatonin synthesis in the mammalian pineal gland: the critical role of serotonin acetylation. Cell Tissue Res 309, 127-137. https://doi.org/10.1007/s00441-002-0579-y
  22. Garcia-Maurino, S., Gonzalez-Haba, M. G., Calvo, J. R., Goberna, R. and Guerrero, J. M. 1998. Involvement of nuclear binding sites for melatonin in the regulation of IL-2 and IL-6 production by human blood mononuclear cells. J Neuroimmunol 92, 76-84. https://doi.org/10.1016/S0165-5728(98)00179-9
  23. Gastel, J. A., Roseboom, P. H., Rinaldi, P. A., Weller, J. L. and Klein, D. C. 1998. Melatonin production: Proteasomal proteolysis in serotonin N-acetyl transferase regulation. Science 279, 1358-1360. https://doi.org/10.1126/science.279.5355.1358
  24. Gebauer, F. and Hentze, M. W. 2004. Molecular mechanisms of translational control. Nat Rev Mol Cell Biol 5, 827-835. https://doi.org/10.1038/nrm1488
  25. Hardeland, R. and Fuhrberg, B. 1996. Ubiquitous melatoninpresence and effects in unicells, plants and animals. Trends Comp Biochem Physiol 2, 25-45.
  26. Hardeland, R. and Poeggeler, B. 2003. Non-vertebrate melatonin. J Pineal Res 34, 233-241. https://doi.org/10.1034/j.1600-079X.2003.00040.x
  27. Hardin, P. E., Hall, J. C. and Rosbash, M. 1990. Feedback of dorsophila perios gene product on circadian cycling of its messenger RNA levels. Nature 343, 536-640. https://doi.org/10.1038/343536a0
  28. Hajak, G., Rodenbeck, A., Staedt, J., Bandelow, B., Huether, G. and Rüther, E.1995. Nocturnal plasma melatonin in patients suffering from chronic primary insomnia. J Pineal Res 19, 116-122. https://doi.org/10.1111/j.1600-079X.1995.tb00179.x
  29. Hershko, L. A. and Ciechanover, A. 1996. Ubiquitination occurs via amino group of lysines in target proteins and is required to target many proteins for proteasomal degradation. Annu Rev Biochem 61, 761.
  30. Kalsbeek, A., Garidou, M. L., Palm, I. F.,Van der Vliet, J., Simonneaux, V., Pevet, P. and Buijs, R. M. 2000. Melatonin sees the light: blocking GABA-ergic transmission in the paraventricular nucleus induces daytime secretion of melatonin. Eur J Neurosci 12, 3146-3154. https://doi.org/10.1046/j.1460-9568.2000.00202.x
  31. Kim, T. D., Kim, J. S., Kim, J. H., Chae, H. D., Woo, K. C. and Kim, K. T. 2005. Rhythmic serotonin N-acetyltransferase mRNA degradation is essential for the maintenance of its circadian oscillation. Mol Cell Biol 25, 3232-3246. https://doi.org/10.1128/MCB.25.8.3232-3246.2005
  32. Kim, T. D., Woo, K. C., Cho, S., Ha, D. C., Jang, S. K. and Kim, K. T. 2007. Rhythmic control of AANAT translation by hnRNP Q in circadian melatonin production. Genes Dev 21, 797-810. https://doi.org/10.1101/gad.1519507
  33. Klein, D. C. 1985. Photoperiodism, Melatonin and the Pineal, pp. 38-56, Ciba Foundation symposium 117., Ciba Foundation: Newark, NJ 07101, USA.
  34. Klein, D. C. and Moore, R. Y. 1979. Pineal N-acetyltransferase and hydroxyindole- O-methyltransferase: control by the retinohypothalamic tract and the suprachiasmatic nucleus. Brain Res 174, 245-262. https://doi.org/10.1016/0006-8993(79)90848-5
  35. Klein, D. C. 2004. The 2004 Aschoff / Pittendrigh lecture: Theory of the origin of the pineal gland-- a tale of conflict and resolution. J Biol Rhythms 19, 264-279. https://doi.org/10.1177/0748730404267340
  36. Korf, H. W., Schomerus, C. and Stehle, J. H. 1998. The pineal organ, its hormone melatonin and the photoneuroendocrine system. Adv Anat Embryol Cell Biol 146, 1-100. https://doi.org/10.1007/978-3-642-58932-4_1
  37. Lavie, P. 1997. Melatonin: role in gating nocturnal rise in sleep propensity. J Biol Rhythms 12, 657-665. https://doi.org/10.1177/074873049701200622
  38. Lewis, A. J., Kerenyi, A. N. and Feuer, G. 1990. Neuropharmacology of pineal secretions. Drug Metab Interact 8, 247-312.
  39. Lewy, A. J., Ahmed, S., Latham Jackson, J. M. and Sack, R. L. 1992. Melatonin shifts human circadian rhythms according to a phase–response curve. Chronobiol Int 9, 380-392. https://doi.org/10.3109/07420529209064550
  40. Lewy, A. J., Hasler, B. P., Emens, J. S. and Sack, R. L. 2001. Pretreatment circadian period in free-running blind people may predict the phase angle of entrainment to melatonin. Neurosci Lett 313, 158-160. https://doi.org/10.1016/S0304-3940(01)02261-3
  41. Lewy, A. J., Sack, R. L. and White, D. M. 1987. The phase-shift hypothesis for bright light’s therapeutic mechanism of action: theoretical considerations and experimental evidence. Psychopharmacol 23, 349-353.
  42. Lewy, A. J., Wehr, T. A., Newsome, D. A. and Markey, S. P. 1980. Light suppresses melatonin secretion in humans. Science 210, 1267-1269. https://doi.org/10.1126/science.7434030
  43. Liu, C., Fukuhara, C., Iuvone, P. M. and Tosini, G. 2004. Localization of Aa-nat mRNA in the rat retina by fluorescence in situ hybridization and laser capture microdissection. Cell Tissue Res 315, 197-201. https://doi.org/10.1007/s00441-003-0822-1
  44. Maestroni, G. J. 1993. The immunoendocrine role of melatonin. J Pineal Res 14, 1-10. https://doi.org/10.1111/j.1600-079X.1993.tb00478.x
  45. McIntyre, I. M., Norman, T. R. and Burrows, G. D. 1989. Human melatonin suppression by light is intensity dependent. J Pineal Res 6, 151-156.
  46. Meijer, J. H. and Rietveld, W. J. 1989. The neurophysiology of the suprachiasmatic circadian pacemaker in rodents. Physiol Rev 69, 671-702.
  47. Pandi-Perumal, S. R., Zisapel, N., Srinivasan, V. and Cardinali, D. P. 2005. Melatonin and sleep in aging population. Exp Gerontol 40, 911-925. https://doi.org/10.1016/j.exger.2005.08.009
  48. Pappolla, M. A., Chyan, Y. J., Frangione, B., Ghiso, J. and Reiter, R. J. 2000. An assessment of the antioxidant and antiamyloidogenic properties of melatonin: implications for Alzheimer's disease. J Neural Trans 107, 203-231. https://doi.org/10.1007/s007020050018
  49. Partonen, T. 1998. Extrapineal melatonin and exogenous serotonin in seasonal affective disorder. Med Hypotheses 51, 441-442. https://doi.org/10.1016/S0306-9877(98)90042-1
  50. Poon, A. M. and Pang, S. F. 1996. Melatonin: A universal photoperiodic signal with diverse action. Front Horm Res 21, 71-83.
  51. Price, D. M., Kanyo, R., Steinberg, N., Chik, C. L. and Ho, A. K. 2009. Nocturnal activation of aurora C in rat pineal gland: its role in the norepinephrine-induced phosphorylation of histone H3 and gene expression. Endocrinology 150, 2334-2341. https://doi.org/10.1210/en.2008-1507
  52. Reiter, R. J. 1998. Cytoprotective properties of melatonin: presumed association with oxidative damage and aging. Nutrition 14, 691-696. https://doi.org/10.1016/S0899-9007(98)00064-1
  53. Reppert, S. M., Weaver, D. R. and Ebisawa, T. 1994. Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. Neuron 13, 1177-1185. https://doi.org/10.1016/0896-6273(94)90055-8
  54. Rosenthal, N. E., Sack, D. A., Gillin, J. C., Davenport, Y., Mueller, P. S. and Wehr, T. A. 1984. Seasonal affective disorder: a description of the syndrome and preliminary findings with light therapy. Arch Gen Psychiatry 41, 72-80. https://doi.org/10.1001/archpsyc.1984.01790120076010
  55. Shochat, T., Haimov, I. and Lavie, P. 1998. Melatonin--the key to the gate of sleep. Ann Med 30, 109-114. https://doi.org/10.3109/07853899808999392
  56. Slominski, A., Fischer, T. W., Zmijewski, M. A., Wortsman, J., Slominski, R. M. and Tobin, D. J. 2005. On the role of melatonin in skin physiology and pathology. Endocrine 27, 137-148. https://doi.org/10.1385/ENDO:27:2:137
  57. Srinivasan, V., Maestroni, G. J. M., Cardinali, D. P., Esquifino, A. I., Pandi-Perumal, S. and Miller, S. C. 2005. Melatonin, immune function and aging. Immune Ageing 2, 17. https://doi.org/10.1186/1742-4933-2-17
  58. Srinivasan, V., Pandi-Perumal, S. R., Maestroni, G. J., Esquifino, A. I., Hardeland, R. and Cardinali, D. P. 2005. Role of melatonin in neurodegenerative diseases. Neurotox Res 7, 293-318. https://doi.org/10.1007/BF03033887
  59. Strassman, R. J., Qualls, C. R., Lisansky, E. J. and Peake, G. T. 1991. Elevated rectal temperature produced by all-night bright light is reversed by melatonin infusion in men. J Appl Physiol 71, 2178-2182.
  60. Takahashi, J. S. 1994. Circadian rhythms.ICER is nicer at night (sir!). Curr Biol 4, 165-168. https://doi.org/10.1016/S0960-9822(94)00040-0
  61. Takemori, H., Kajimura, J. and Okamoto, M. 2000. TORCSIK cascade regulates CREB activity through the basic leucine zipper domain. FEBS J 274, 3202-3209.
  62. Terman, J. S., Terman, M., Lo, E. S. and Cooper, T. B. 2001. Circadian time of morning light administration and therapeutic response in winter depression. Arch Gen Psychiatry 58, 69-75. https://doi.org/10.1001/archpsyc.58.1.69
  63. Veerman, D., Imholz, B., Wieling, W., Wesseling, K. and Van Montfrans, G. A. 1995. Circadian profile of sytemic hemodynamics. Hypertension 26, 55-59. https://doi.org/10.1161/01.HYP.26.1.55
  64. Waldhauser, F., Boepple, P. A., Schemper, M., Mansfield, M. J. and Crowley, W. F. Jr. 1981. Serum melatonin in central precocious puberty is lower than in age-matched prepubertal children. J Clin Endocrinol Metab 73, 793-796.
  65. Wehr, T. A., Duncan, W. C. Jr., Sher, L., Aeschbach, D., Schwartz, P. J., Turner, E. H., Postolache, T. T. and Rosenthal, N. E. 2001. A circadian signal of change of season in patients with Seasonal Affective Disorder. Arch Gen Psychiatry 58, 1108-1114. https://doi.org/10.1001/archpsyc.58.12.1108
  66. Wehr, T. A., Sack, D. A., Jacobsen, F., Tamarkin, L., Arendt, J. and Rosenthal, N. E. 1986. Phototherapy of seasonal affective disorder: time of day and suppression of melatonin are not critical for antidepressant effect. Arch Gen Psychiatry 43, 870-875. https://doi.org/10.1001/archpsyc.1986.01800090060008
  67. Wetterberg, L. 1985. Melatonin and affective disorders. Ciba Found Symp 117, 235-265.
  68. Wikner, J., Hirsch, U., Wetterberg, L. and Röjdmark, S. 1998. Fibromyalgia--a syndrome associated with decreased nocturnal melatonin secretion. Clin Endocrinol 49, 179-183. https://doi.org/10.1046/j.1365-2265.1998.00503.x

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