Melatonin as a Potent and Inducible Endogenous Antioxidant: Synthesis and Metabolism

Springer Science and Business Media LLC - Tập 20 Số 10 - Trang 18886-18906
Dun-Xian Tan1, Lucien C. Manchester1, Eduardo Esteban‐Zubero1, Zhou Zhou1, Rüssel J. Reiter1
1Department of Cellular and Structural Biology, Health Science Center, University of Texas, San Antonio, TX 78229, USA

Tóm tắt

Melatonin is a tryptophan-derived molecule with pleiotropic activities. It is present in almost all or all organisms. Its synthetic pathway depends on the species in which it is measured. For example, the tryptophan to melatonin pathway differs in plants and animals. It is speculated that the melatonin synthetic machinery in eukaryotes was inherited from bacteria as a result of endosymbiosis. However, melatonin’s synthetic mechanisms in microorganisms are currently unknown. Melatonin metabolism is highly complex with these enzymatic processes having evolved from cytochrome C. In addition to its enzymatic degradation, melatonin is metabolized via pseudoenzymatic and free radical interactive processes. The metabolic products of these processes overlap and it is often difficult to determine which process is dominant. However, under oxidative stress, the free radical interactive pathway may be featured over the others. Because of the complexity of the melatonin degradative processes, it is expected that additional novel melatonin metabolites will be identified in future investigations. The original and primary function of melatonin in early life forms such as in unicellular organisms was as a free radical scavenger and antioxidant. During evolution, melatonin was selected as a signaling molecule to transduce the environmental photoperiodic information into an endocrine message in multicellular organisms and for other purposes as well. As an antioxidant, melatonin exhibits several unique features which differ from the classic antioxidants. These include its cascade reaction with free radicals and its capacity to be induced under moderate oxidative stress. These features make melatonin a potent endogenously-occurring antioxidant that protects organisms from catastrophic oxidative stress.

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Tài liệu tham khảo

Lerner, 1958, Isolation of melatonin, a pineal factor that lightens melanocytes, J. Am. Soc., 80, 2587, 10.1021/ja01543a060

Lerner, 1959, Pigment cell regulatory factors, J. Investig. Dermatol., 32, 211, 10.1038/jid.1959.38

Nordlund, 1977, The effects of oral melatonin on skin color and on the release of pituitary hormones, J. Clin. Endocrinol. Metab., 45, 768, 10.1210/jcem-45-4-768

Reiter, 1991, Melatonin: The chemical expression of darkness, Mol. Cell. Endocrinol., 79, C153, 10.1016/0303-7207(91)90087-9

Pelham, 1975, A serum melatonin rhythm in chickens and its abolition by pinealectomy, Endocrinology, 96, 543, 10.1210/endo-96-2-543

Yu, 1981, Persistence of circadian rhythms of melatonin and N-acetylserotonin in the serum of rats after pinealectomy, Neuroendocrinology, 32, 262, 10.1159/000123170

Pevet, 2011, Melatonin: Both master clock output and internal time-giver in the circadian clocks network, J. Physiol., 105, 170

Vriend, 2015, Melatonin feedback on clock genes: A theory involving the proteasome, J. Pineal Res., 58, 1, 10.1111/jpi.12189

Legros, 2014, Melatonin from cerebrospinal fluid but not from blood reaches sheep cerebral tissues under physiological conditions, J. Neuroendocrinol., 26, 151, 10.1111/jne.12134

Reiter, 2014, Delivery of pineal melatonin to the brain and SCN: Role of canaliculi, cerebrospinal fluid, tanycytes and Virchow-Robin perivascular spaces, Brain Struct. Funct., 219, 1873, 10.1007/s00429-014-0719-7

Stehle, 2002, Mammalian melatonin receptors: Molecular biology and signal transduction, Cell Tiss. Res., 309, 151, 10.1007/s00441-002-0581-4

Weaver, 1996, The Mel1a melatonin receptor gene is expressed in human suprachiasmatic nuclei, Neuroreport, 8, 109, 10.1097/00001756-199612200-00022

Reiter, 2011, The photoperiod, circadian regulation and chronodisruption: The requisite interplay between the suprachiasmatic nuclei and the pineal and gut melatonin, J. Physiol. Pharmacol., 62, 269

Pevet, 2006, Melatonin in the multi-oscillatory mammalian circadian world, Chronobiol. Int., 23, 39, 10.1080/07420520500482074

Stehle, 2003, Melatonin: A clock-output, a clock-input, J. Neuroendocrinol., 15, 383, 10.1046/j.1365-2826.2003.01001.x

Manchester, 1995, Melatonin immunoreactivity in the photosynthetic prokaryote Rhodospirillum rubrum: Implications for an ancient antioxidant system, Cell Mol. Biol. Res., 41, 391

Tilden, 1997, Melatonin production in an aerobic photosynthetic bacterium: An evolutionarily early association with darkness, J. Pineal Res., 22, 102, 10.1111/j.1600-079X.1997.tb00310.x

Roopin, 2013, Occurrence, diel patterns, and the influence of melatonin on the photosynthetic performance of cultured Symbiodinium, J. Pineal Res., 55, 89, 10.1111/jpi.12046

Tan, 2010, The changing biological roles of melatonin during evolution: From an antioxidant to signals of darkness, sexual selection and fitness, Biol. Rev., 85, 607, 10.1111/j.1469-185X.2009.00118.x

Tosches, 2014, Melatonin signaling controls circadian swimming behavior in marine zooplankton, Cell, 159, 46, 10.1016/j.cell.2014.07.042

Wang, 2013, A meta-analysis on dose-response relationship between night shift work and the risk of breast cancer, Ann. Oncol., 24, 2724, 10.1093/annonc/mdt283

Akerstedt, 2015, Night work and breast cancer in women: A Swedish cohort study, BMJ Open, 5, e008127, 10.1136/bmjopen-2015-008127

Papantoniou, K., Castano-Vinyals, G., Espinosa, A., Aragones, N., Perez-Gomez, B., Burgos, J., Gomez-Acebo, I., Llorca, J., Peiro, R., and Jimenez-Moleon, J.J. (2014). Night shift work, chronotype and prostate cancer risk in the MCC-Spain case-control study. Int. J. Cancer.

Mirick, 2013, Night shift work and levels of 6-sulfatoxymelatonin and cortisol in men, Cancer Epidemiol Biomark. Prev., 22, 1079, 10.1158/1055-9965.EPI-12-1377

Mao, 2012, Circadian gating of epithelial-to-mesenchymal transition in breast cancer cells via melatonin-regulation of GSK3β, Mol. Endocrinol., 26, 1808, 10.1210/me.2012-1071

Stevens, 2007, Meeting report: the role of environmental lighting and circadian disruption in cancer and other diseases, Environ. Health Perspect., 115, 1357, 10.1289/ehp.10200

Brainard, 1982, Pineal melatonin in syrian hamsters: Circadian and seasonal rhythms in animals maintained under laboratory and natural conditions, Neuroendocrinology, 35, 342, 10.1159/000123405

Reiter, 1993, The melatonin rhythm: both a clock and a calendar, Experientia, 49, 654, 10.1007/BF01923947

Ralph, 1982, Delayed effect of pinealectomy on hibernation of the golden-mantled ground squirrel, Int. J. Biometeorol., 26, 311, 10.1007/BF02219502

Reiter, 1974, Influence of pinealectomy on the breeding capability of hamsters maintained under natural photoperiodic and temperature conditions, Neuroendocrinology, 13, 366, 10.1159/000122222

Nelson, 1987, Pinealectomy blocks vernal courtship behavior in red-sided garter snakes, Physiol. Behav., 39, 231, 10.1016/0031-9384(87)90014-X

Eder, 1997, Melatonin: Occurrence and daily rhythm in Chenopodium rubrum, Phytochemistry, 44, 1407, 10.1016/S0031-9422(96)00568-7

Murch, 2000, Tryptophan is a precursor for melatonin and serotonin biosynththesis in in vitro regenerated St. John’s wort (Hypericum perforatum L. cv. Anthos) plants, Plant Cell Rep., 19, 698, 10.1007/s002990000206

Afreen, 2006, Melatonin in Glycyrrhiza uralensis: response of plant roots to spectral quality of light and UV-B radiation, J. Pineal Res., 41, 108, 10.1111/j.1600-079X.2006.00337.x

Tan, 2007, Novel rhythms of N1-acetyl-N2-formyl-5-methoxykynuramine and its precursor melatonin in water hyacinth: Importance for phytoremediation, FASEB J., 21, 1724, 10.1096/fj.06-7745com

Tan, 2012, Functional roles of melatonin in plants, and perspectives in nutritional and agricultural science, J. Exp. Bot., 63, 577, 10.1093/jxb/err256

Reiter, 2015, Phytomelatonin: Assisting plants to survive and thrive, Molecules, 20, 7396, 10.3390/molecules20047396

Tan, 2014, Fundamental issues related to the origin of melatonin and melatonin isomers during evolution: Relation to their biological functions, Int. J. Mol. Sci., 15, 15858, 10.3390/ijms150915858

Foulkes, 1997, Rhythmic transcription: The molecular basis of circadian melatonin synthesis, Trends Neurosci., 20, 487, 10.1016/S0166-2236(97)01109-0

Ganguly, 2001, Role of a pineal cAMP-operated arylalkylamine N-acetyltransferase/14-3-3-binding switch in melatonin synthesis, Proc. Nat. Acad. Sci. USA, 98, 8083, 10.1073/pnas.141118798

Szewczuk, 2008, Analysis of serotonin N-acetyltransferase regulation in vitro and in live cells using protein semisynthesis, Biochemistry, 47, 10407, 10.1021/bi801189d

Borjigin, 2008, Application of long-term microdialysis in circadian rhythm research, Pharmacol. Biochem. Behav., 90, 148, 10.1016/j.pbb.2007.10.010

Johnston, 2004, Rhythmic melatonin secretion does not correlate with the expression of arylalkylamine N-acetyltransferase, inducible cyclic amp early repressor, period1 or cryptochrome1 mRNA in the sheep pineal, Neuroscience, 124, 789, 10.1016/j.neuroscience.2004.01.011

Liu, 2005, N-acetyltransferase is not the rate-limiting enzyme of melatonin synthesis at night, J. Pineal Res., 39, 91, 10.1111/j.1600-079X.2005.00223.x

Ceinos, 2004, Analysis of adrenergic regulation of melatonin synthesis in Siberian hamster pineal emphasizes the role of HIOMT, Neuro-Signals, 13, 308, 10.1159/000081966

Pang, 1980, Melatonin in the retina of rats: A diurnal rhythm, J. Endocrinol., 87, 89, 10.1677/joe.0.0870089

Isorna, 2009, Cloning and expression of arylalkylamine N-acetyltranferase-2 during early development and metamorphosis in the sole Solea senegalensis, Gen. Comp. Endocrinol., 161, 97, 10.1016/j.ygcen.2008.10.007

Isorna, 2011, Identification of two arylalkylamine N-acetyltranferase 1 genes with different developmental expression profiles in the flatfish Solea senegalensis, J. Pineal Res., 51, 434, 10.1111/j.1600-079X.2011.00907.x

Falcon, 2014, Drastic neofunctionalization associated with evolution of the timezyme AANAT 500 Mya, Proc. Nat. Acad. Sci. USA, 111, 314, 10.1073/pnas.1312634110

Tan, 2007, One molecule, many derivatives: A never-ending interaction of melatonin with reactive oxygen and nitrogen species?, J. Pineal Res., 42, 28, 10.1111/j.1600-079X.2006.00407.x

Escames, 2014, Extrapineal melatonin: Sources, regulation, and potential functions, Cell Mol. Life Sci., 71, 2997, 10.1007/s00018-014-1579-2

Huether, 1993, The contribution of extrapineal sites of melatonin synthesis to circulating melatonin levels in higher vertebrates, Experientia, 49, 665, 10.1007/BF01923948

Slominski, 2008, Melatonin in the skin: Synthesis, metabolism and functions, Trends Endocrinol. Metab., 19, 17, 10.1016/j.tem.2007.10.007

Tan, 2013, Mitochondria and chloroplasts as the original sites of melatonin synthesis: A hypothesis related to melatonin’s primary function and evolution in eukaryotes, J. Pineal Res., 54, 127, 10.1111/jpi.12026

Venegas, 2012, Extrapineal melatonin: Analysis of its subcellular distribution and daily fluctuations, J. Pineal Res., 52, 217, 10.1111/j.1600-079X.2011.00931.x

Hattori, 1995, Identification of melatonin in plants and its effects on plasma melatonin levels and binding to melatonin receptors in vertebrates, Biochem. Mol. Biol. Int., 35, 627

Dubbels, 1995, Melatonin in edible plants identified by radioimmunoassay and by high performance liquid chromatography-mass spectrometry, J. Pineal Res., 18, 28, 10.1111/j.1600-079X.1995.tb00136.x

Byeon, 2014, Cellular localization and kinetics of the rice melatonin biosynthetic enzymes SNAT and ASMT, J. Pineal Res., 56, 107, 10.1111/jpi.12103

Roseboom, 1998, Natural melatonin “knockdown” in C57BL/6J mice: Rare mechanism truncates serotonin N-acetyltransferase, Mol. Brain Res., 63, 189, 10.1016/S0169-328X(98)00273-3

Park, 2013, Transcriptional suppression of tryptamine 5-hydroxylase, a terminal serotonin biosynthetic gene, induces melatonin biosynthesis in rice (Oryza sativa L.), J. Pineal Res., 55, 131, 10.1111/jpi.12053

Lee, 2014, Cloning of Arabidopsis serotonin N-acetyltransferase and its role with caffeic acid O-methyltransferase in the biosynthesis of melatonin in vitro despite their different subcellular localizations, J. Pineal Res., 57, 418, 10.1111/jpi.12181

Byeon, 2014, Caffeic acid O-methyltransferase is involved in the synthesis of melatonin by methylating N-acetylserotonin in Arabidopsis, J. Pineal Res., 57, 219, 10.1111/jpi.12160

Hardeland, 2003, Non-vertebrate melatonin, J. Pineal Res., 34, 233, 10.1034/j.1600-079X.2003.00040.x

Torija, 2012, Production of melatonin by Saccharomyces strains under growth and fermentation conditions, J. Pineal Res., 53, 219, 10.1111/j.1600-079X.2012.00990.x

Medina, 2014, Alcoholic fermentation induces melatonin synthesis in orange juice, J. Pineal Res., 56, 31, 10.1111/jpi.12093

Ordonez, 2013, Melatonin is formed during winemaking at safe levels of biogenic amines, Food Chem.Toxicol., 57, 140, 10.1016/j.fct.2013.03.014

Kocadagli, 2014, Determination of melatonin and its isomer in foods by liquid chromatography tandem mass spectrometry, Food Chem., 153, 151, 10.1016/j.foodchem.2013.12.036

Yilmaz, 2014, Formation of melatonin and its isomer during bread dough fermentation and effect of baking, J. Agric. Food Chem., 62, 2900, 10.1021/jf500294b

Tan, 2012, Emergence of naturally occurring melatonin isomers and their proposed nomenclature, J. Pineal Res., 53, 113, 10.1111/j.1600-079X.2012.00979.x

Vitalini, 2013, Melatonin, melatonin isomers and stilbenes in Italian traditional grape products and their antiradical capacity, J. Pineal Res., 54, 322, 10.1111/jpi.12028

Gardana, 2014, “Melatonin isomer” in wine is not an isomer of the melatonin but tryptophan-ethylester, J. Pineal Res., 57, 435, 10.1111/jpi.12183

Knight, E.M., Zhu, J., Forster, J., and Luo, H. (2013). Microorganisms for the Production of Melatonin. (20150024440 A1), WO Patent.

Byeon, 2013, Molecular cloning and functional analysis of serotonin N-acetyltransferase from the cyanobacterium Synechocystis sp. PCC 6803, J. Pineal Res., 55, 371, 10.1111/jpi.12080

Semak, 2008, Metabolism of melatonin by cytochrome P450s in rat liver mitochondria and microsomes, J. Pineal Res., 45, 515, 10.1111/j.1600-079X.2008.00630.x

Dibrova, 2013, Evolution of cytochrome bc complexes: From membrane-anchored dehydrogenases of ancient bacteria to triggers of apoptosis in vertebrates, Biochim. Biophys. Acta, 1827, 1407, 10.1016/j.bbabio.2013.07.006

Tesoriere, 2001, Oxidation of melatonin by oxoferryl hemoglobin: A mechanistic study, Free Radic. Res., 35, 633, 10.1080/10715760100301161

Tan, 2014, Cyclic-3-hydroxymelatonin (C3HOM), a potent antioxidant, scavenges free radicals and suppresses oxidative reactions, Curr. Med. Chem., 21, 1557, 10.2174/0929867321666131129113146

Hardeland, 2009, Kynuramines, metabolites of melatonin and other indoles: The resurrection of an almost forgotten class of biogenic amines, J. Pineal Res., 47, 109, 10.1111/j.1600-079X.2009.00701.x

Szewczyk, 2015, The levels of melatonin and its metabolites in conditioned corn (Zea mays L.) and cucumber (Cucumis sativus L.) seeds during storage, Acta Physiol. Plant, 37, 1

Byeon, Y., Tan, D.X., Reiter, R.J., and Back, K. (2015). Predominance of 2-hydroxymelatonin over melatonin in plants. J. Pineal Res.

Byeon, 2015, Molecular cloning of melatonin 2-hydroxylase responsible for 2-hydroxymelatonin production in rice (Oryza sativa), J. Pineal Res., 58, 343, 10.1111/jpi.12220

Tan, 2003, Mechanistic and comparative studies of melatonin and classic antioxidants in terms of their interactions with the ABTS cation radical, J. Pineal Res., 34, 249, 10.1034/j.1600-079X.2003.00037.x

Lowes, 2013, Antioxidants that protect mitochondria reduce interleukin-6 and oxidative stress, improve mitochondrial function, and reduce biochemical markers of organ dysfunction in a rat model of acute sepsis, Br. J. Anaesth., 110, 472, 10.1093/bja/aes577

Gitto, 2001, Individual and synergistic antioxidative actions of melatonin: Studies with vitamin E, vitamin C, glutathione and desferrioxamine (desferoxamine) in rat liver homogenates, J. Pharm. Pharmacol., 53, 1393, 10.1211/0022357011777747

Sharma, 2006, Melatonin prevents X-ray irradiation induced oxidative damagein peripheral blood and spleen of the seasonally breeding rodent, Funambulus pennanti during reproductively active phase, Int. J. Radiat. Biol., 82, 411, 10.1080/09553000600774105

Tunez, 2007, Comparison of melatonin, vitamin E and l-carnitine in the treatment of neuro- and hepatotoxicity induced by thioacetamide, Cell Biochem. Funct., 25, 119, 10.1002/cbf.1276

Elbe, 2015, Amelioration of streptozotocin-induced diabetic nephropathy by melatonin, quercetin, and resveratrol in rats, Hum. Exp. Toxicol., 34, 100, 10.1177/0960327114531995

Ortiz, 2013, Fish oil, melatonin and vitamin E attenuates midbrain cyclooxygenase-2 activity and oxidative stress after the administration of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine, Metab. Brain Dis., 28, 705, 10.1007/s11011-013-9416-0

Galano, 2015, Melatonin and its metabolites as copper chelating agents and their role in inhibiting oxidative stress: A physicochemical analysis, J. Pineal Res., 58, 107, 10.1111/jpi.12196

Reiter, 2014, Melatonin reduces lipid peroxidation and membrane viscosity, Front Physiol., 5, 377, 10.3389/fphys.2014.00377

Galano, 2014, Computational study on the kinetics and mechanism of the carbaryl + OH reaction, J. Phys. Chem. A, 118, 7776, 10.1021/jp507244s

Ressmeyer, 2003, Antioxidant properties of the melatonin metabolite N1-acetyl-5-methoxykynuramine (AMK): Scavenging of free radicals and prevention of protein destruction, Redox Rep., 8, 205, 10.1179/135100003225002709

Mayo, 2005, Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxy-kynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophages, J. Neuroimmunol., 165, 139, 10.1016/j.jneuroim.2005.05.002

Galano, 2013, On the free radical scavenging activities of melatonin’s metabolites, AFMK and AMK, J. Pineal Res., 54, 245, 10.1111/jpi.12010

Tan, 2001, N1-acetyl-N2-formyl-5-methoxykynuramine, a biogenic amine and melatonin metabolite, functions as a potent antioxidant, FASEB J., 15, 2294, 10.1096/fj.01-0309fje

Johns, 2014, Theoretical insight into the antioxidant properties of melatonin and derivatives, Org. Biomol. Chem., 12, 7820, 10.1039/C4OB01396D

Janjetovic, 2014, Melatonin and its metabolites ameliorate ultraviolet B-induced damage in human epidermal keratinocytes, J. Pineal Res., 57, 90, 10.1111/jpi.12146

Kelly, 1984, N-acetyl-5-methoxy kynurenamine, a brain metabolite of melatonin, is a potent inhibitor of prostaglandin biosynthesis, Biochem. Biophys. Res. Commun., 121, 372, 10.1016/0006-291X(84)90732-0

Mauriz, 2013, A review of the molecular aspects of melatonin’s anti-inflammatory actions: Recent insights and new perspectives, J. Pineal Res., 54, 1, 10.1111/j.1600-079X.2012.01014.x

Manda, 2007, AFMK, a melatonin metabolite, attenuates X-ray-induced oxidative damage to DNA, proteins and lipids in mice, J. Pineal Res., 42, 386, 10.1111/j.1600-079X.2007.00432.x

Manda, 2008, Space radiation-induced inhibition of neurogenesis in the hippocampal dentate gyrus and memory impairment in mice: Ameliorative potential of the melatonin metabolite, AFMK, J. Pineal Res., 45, 430, 10.1111/j.1600-079X.2008.00611.x

Tan, 2000, Significance of melatonin in antioxidative defense system: Reactions and products, Biol. Signals Recept., 9, 137, 10.1159/000014635

Escribano, 2014, The role of melatonin in multiple sclerosis, Huntington’s disease and cerebral ischemia, CNS Neurol. Disord. Drug Targets, 13, 1096, 10.2174/1871527313666140806160400

Mediavilla, 2010, Clinical uses of melatonin: Evaluation of human trials, Curr. Med. Chem., 17, 2070, 10.2174/092986710791233689

Akhavan, 2011, Wrapping bacteria by graphene nanosheets for isolation from environment, reactivation by sonication, and inactivation by near-infrared irradiation, J. Phys. Chem. B, 115, 6279, 10.1021/jp200686k

Esfandiar, 2011, Melatonin as a powerful bio-antioxidant for reduction of graphene oxide, J. Mater. Chem., 21, 10907, 10.1039/c1jm10151j

Reiter, 1986, Normal patterns of melatonin levels in the pineal gland and body fluids of humans and experimental animals, J. Neural Transm., 21, 35

Sack, 1986, Human melatonin production decreases with age, J. Pineal Res., 3, 379, 10.1111/j.1600-079X.1986.tb00760.x

Reiter, 1980, Pineal melatonin rhythm: Reduction in aging Syrian hamsters, Science, 210, 1372, 10.1126/science.7434032

Hardeland, 2013, Melatonin and the theories of aging: A critical appraisal of melatonin’s role in antiaging mechanisms, J. Pineal Res., 55, 325, 10.1111/jpi.12090

Ebihara, 1986, Genetic control of melatonin synthesis in the pineal gland of the mouse, Science, 231, 491, 10.1126/science.3941912

Troiani, 1988, Neither the pituitary gland nor the sympathetic nervous system is responsible for eliciting the large drop in elevated rat pineal melatonin levels due to swimming, J. Neural Transm., 74, 149, 10.1007/BF01244781

Ueck, 1988, Transient reduction in pineal melatonin levels but not N-acetyltransferase activity in rats forced to swim for 15 minutes at night, Neuroendocrinol. Lett., 10, 81

Liu, 1999, Decreased melatonin levels in postmortem cerebrospinal fluid in relation to aging, Alzheimer’s disease, and apolipoprotein E-epsilon4/4 genotype, J. Clin. Endocrinol. Metab., 84, 323

Maurizi, 1997, Loss of intraventricular fluid melatonin can explain the neuropathology of Alzheimer’s disease, Med. Hypotheses, 49, 153, 10.1016/S0306-9877(97)90220-6

Zhou, 2003, Early neuropathological Alzheimer’s changes in aged individuals are accompanied by decreased cerebrospinal fluid melatonin levels, J. Pineal Res., 35, 125, 10.1034/j.1600-079X.2003.00065.x

Dzida, 2013, Alteration in diurnal and nocturnal melatonin serum level in patients with chronic heart failure, Ann. Agric. Environ. Med., 20, 745

Sakotnik, 1999, Decreased melatonin synthesis in patients with coronary artery disease, Eur. Heart J., 20, 1314, 10.1053/euhj.1999.1527

Reiter, 2012, Decreased level of melatonin in serum predicts left ventricular remodelling after acute myocardial infarction, J. Pineal Res., 53, 319, 10.1111/j.1600-079X.2012.01001.x

Pohjanvirta, 1989, TCDD reduces serum melatonin levels in Long-Evans rats, Pharmacol. Toxicol., 65, 239, 10.1111/j.1600-0773.1989.tb01164.x

Linden, 1991, TCDD decreases rapidly and persistently serum melatonin concentration without morphologically affecting the pineal gland in TCDD-resistant Han/Wistar rats, Pharmacol. Toxicol., 69, 427, 10.1111/j.1600-0773.1991.tb01325.x

Pohjanvirta, 1996, Mechanism by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reduces circulating melatonin levels in the rat, Toxicology, 107, 85, 10.1016/0300-483X(95)03241-7

Uzun, 2012, The effect of acute swimming exercise on plasma melatonin levels in rats, Bratislav. Lekar. Listy, 113, 64

Troiani, 1988, Swimming depresses nighttime melatonin content without changing N-acetyltransferase activity in the rat pineal gland, Neuroendocrinology, 47, 55, 10.1159/000124891

Oxenkrug, 1985, Stress-induced synthesis of melatonin: possible involvement of the endogenous monoamine oxidase inhibitor (tribulin), Life Sci., 37, 1743, 10.1016/0024-3205(85)90303-0

Stokkan, 1991, Low temperature stimulates pineal activity in Syrian hamsters, J. Pineal Res., 10, 43, 10.1111/j.1600-079X.1991.tb00008.x

Stokkan, 1991, Endocrine and metabolic effects of life-long food restriction in rats, Acta Endocrinol., 125, 93

Mattison, 2003, Calorie restriction in rhesus monkeys, Exp. Gerontol., 38, 35, 10.1016/S0531-5565(02)00146-8

Fontana, 2010, Effects of long-term calorie restriction and endurance exercise on glucose tolerance, insulin action, and adipokine production, Age, 32, 97, 10.1007/s11357-009-9118-z

Fontana, 2010, Extending healthy life span—From yeast to humans, Science, 328, 321, 10.1126/science.1172539

Tan, 2005, Physiological ischemia/reperfusion phenomena and their relation to endogenous melatonin production: A hypothesis, Endocrine, 27, 149, 10.1385/ENDO:27:2:149

Jaworek, 2003, Protective effect of melatonin and its precursor l-tryptophan on acute pancreatitis induced by caerulein overstimulation or ischemia/reperfusion, J. Pineal Res., 34, 40, 10.1034/j.1600-079X.2003.02937.x

Arnao, 2009, Chemical stress by different agents affects the melatonin content of barley roots, J. Pineal Res., 46, 295, 10.1111/j.1600-079X.2008.00660.x

Tal, 2011, Melatonin as an antioxidant and its semi-lunar rhythm in green macroalga Ulva sp., J. Exp. Bot., 62, 1903, 10.1093/jxb/erq378

Arnao, 2013, Growth conditions determine different melatonin levels in Lupinus albus L., J. Pineal Res., 55, 149, 10.1111/jpi.12055

Byeon, 2014, Melatonin synthesis in rice seedlings in vivo is enhanced at high temperatures and under dark conditions due to increased serotonin N-acetyltransferase and N-acetylserotonin methyltransferase activities, J. Pineal Res., 56, 189, 10.1111/jpi.12111

Lei, 2013, Identification of genes for melatonin synthetic enzymes in “Red Fuji” apple (Malus domestica Borkh.cv.Red) and their expression and melatonin production during fruit development, J. Pineal Res., 55, 443, 10.1111/jpi.12096

Park, 2013, Functional analyses of three ASMT gene family members in rice plants, J. Pineal Res., 55, 409, 10.1111/jpi.12088

Kang, 2013, Molecular cloning of rice serotonin N-acetyltransferase, the penultimate gene in plant melatonin biosynthesis, J. Pineal Res., 55, 7, 10.1111/jpi.12011

Fuhrberg, 1997, Dramatic rises of melatonin and 5-methoxytryptamine in Gonyaulax exposed to decreased temperature, Biol. Rhythm. Res., 28, 144, 10.1076/brhm.28.1.144.12978