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      Melatonin Synthesis and Function: Evolutionary History in Animals and Plants

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          Abstract

          Melatonin is an ancient molecule that can be traced back to the origin of life. Melatonin's initial function was likely that as a free radical scavenger. Melatonin presumably evolved in bacteria; it has been measured in both α-proteobacteria and in photosynthetic cyanobacteria. In early evolution, bacteria were phagocytosed by primitive eukaryotes for their nutrient value. According to the endosymbiotic theory, the ingested bacteria eventually developed a symbiotic association with their host eukaryotes. The ingested α-proteobacteria evolved into mitochondria while cyanobacteria became chloroplasts and both organelles retained their ability to produce melatonin. Since these organelles have persisted to the present day, all species that ever existed or currently exist may have or may continue to synthesize melatonin in their mitochondria (animals and plants) and chloroplasts (plants) where it functions as an antioxidant. Melatonin's other functions, including its multiple receptors, developed later in evolution. In present day animals, via receptor-mediated means, melatonin functions in the regulation of sleep, modulation of circadian rhythms, enhancement of immunity, as a multifunctional oncostatic agent, etc., while retaining its ability to reduce oxidative stress by processes that are, in part, receptor-independent. In plants, melatonin continues to function in reducing oxidative stress as well as in promoting seed germination and growth, improving stress resistance, stimulating the immune system and modulating circadian rhythms; a single melatonin receptor has been identified in land plants where it controls stomatal closure on leaves. The melatonin synthetic pathway varies somewhat between plants and animals. The amino acid, tryptophan, is the necessary precursor of melatonin in all taxa. In animals, tryptophan is initially hydroxylated to 5-hydroxytryptophan which is then decarboxylated with the formation of serotonin. Serotonin is either acetylated to N-acetylserotonin or it is methylated to form 5-methoxytryptamine; these products are either methylated or acetylated, respectively, to produce melatonin. In plants, tryptophan is first decarboxylated to tryptamine which is then hydroxylated to form serotonin.

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          Most cited references227

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          Melatonin as an antioxidant: under promises but over delivers.

          Melatonin is uncommonly effective in reducing oxidative stress under a remarkably large number of circumstances. It achieves this action via a variety of means: direct detoxification of reactive oxygen and reactive nitrogen species and indirectly by stimulating antioxidant enzymes while suppressing the activity of pro-oxidant enzymes. In addition to these well-described actions, melatonin also reportedly chelates transition metals, which are involved in the Fenton/Haber-Weiss reactions; in doing so, melatonin reduces the formation of the devastatingly toxic hydroxyl radical resulting in the reduction of oxidative stress. Melatonin's ubiquitous but unequal intracellular distribution, including its high concentrations in mitochondria, likely aid in its capacity to resist oxidative stress and cellular apoptosis. There is credible evidence to suggest that melatonin should be classified as a mitochondria-targeted antioxidant. Melatonin's capacity to prevent oxidative damage and the associated physiological debilitation is well documented in numerous experimental ischemia/reperfusion (hypoxia/reoxygenation) studies especially in the brain (stroke) and in the heart (heart attack). Melatonin, via its antiradical mechanisms, also reduces the toxicity of noxious prescription drugs and of methamphetamine, a drug of abuse. Experimental findings also indicate that melatonin renders treatment-resistant cancers sensitive to various therapeutic agents and may be useful, due to its multiple antioxidant actions, in especially delaying and perhaps treating a variety of age-related diseases and dehumanizing conditions. Melatonin has been effectively used to combat oxidative stress, inflammation and cellular apoptosis and to restore tissue function in a number of human trials; its efficacy supports its more extensive use in a wider variety of human studies. The uncommonly high-safety profile of melatonin also bolsters this conclusion. It is the current feeling of the authors that, in view of the widely diverse beneficial functions that have been reported for melatonin, these may be merely epiphenomena of the more fundamental, yet-to-be identified basic action(s) of this ancient molecule.
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            ISOLATION OF MELATONIN, THE PINEAL GLAND FACTOR THAT LIGHTENS MELANOCYTES1

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              Functions of melatonin in plants: a review.

              The number of studies on melatonin in plants has increased significantly in recent years. This molecule, with a large set of functions in animals, has also shown great potential in plant physiology. This review outlines the main functions of melatonin in the physiology of higher plants. Its role as antistress agent against abiotic stressors, such as drought, salinity, low and high ambient temperatures, UV radiation and toxic chemicals, is analyzed. The latest data on their role in plant-pathogen interactions are also discussed. Both abiotic and biotic stresses produce a significant increase in endogenous melatonin levels, indicating its possible role as effector in these situations. The existence of endogenous circadian rhythms in melatonin levels has been demonstrated in some species, and the data, although limited, suggest a central role of this molecule in the day/night cycles in plants. Finally, another aspect that has led to a large volume of research is the involvement of melatonin in aspects of plant development regulation. Although its role as a plant hormone is still far of from being fully established, its involvement in processes such as growth, rhizogenesis, and photosynthesis seems evident. The multiple changes in gene expression caused by melatonin point to its role as a multiregulatory molecule capable of coordinating many aspects of plant development. This last aspect, together with its role as an alleviating-stressor agent, suggests that melatonin is an excellent prospect for crop improvement.
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                Author and article information

                Contributors
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                17 April 2019
                2019
                : 10
                : 249
                Affiliations
                [1] 1Biocontrol Engineering Research Center of Plant Disease and Pest, Yunnan University , Kunming, China
                [2] 2Biocontrol Engineering Research Center of Crop Disease and Pest, Yunnan University , Kunming, China
                [3] 3School of Life Science, Yunnan University , Kunming, China
                [4] 4State Key Laboratory for Conservation and Utilization of Bio-resources in Yunnan, Yunnan University , Kunming, China
                [5] 5College of Agriculture and Biotechnology, Yunnan Agricultural University , Kunming, China
                [6] 6School of Landscape and Horticulture, Yunnan Vocational and Technical College of Agriculture , Kunming, China
                [7] 7Department of Cell Systems and Anatomy, The University of Texas Health Science Center at San Antonio (UT Health) , San Antonio, TX, United States
                Author notes

                Edited by: Ralf Jockers, Université Paris-Sorbonne, France

                Reviewed by: Maristela Oliveira Poletini, Federal University of Minas Gerais, Brazil; Yves Combarnous, Centre National de la Recherche Scientifique (CNRS), France

                *Correspondence: Russel J. Reiter reiter@ 123456uthscsa.edu

                This article was submitted to Cellular Endocrinology, a section of the journal Frontiers in Endocrinology

                †These authors have contributed equally to this work

                Article
                10.3389/fendo.2019.00249
                6481276
                31057485
                6905a8dc-0b55-4c7a-9e6e-011832ee95f0
                Copyright © 2019 Zhao, Yu, Shen, Liu, Zhao, Sharma and Reiter.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 06 December 2018
                : 29 March 2019
                Page count
                Figures: 5, Tables: 0, Equations: 0, References: 214, Pages: 16, Words: 13323
                Categories
                Endocrinology
                Review

                Endocrinology & Diabetes
                melatonin,evolution,antioxidant,biological rhythms,biosynthesis enzymes,endosymbiosis,regulation of melatonin

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