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Special Issue "Melatonin as an Antioxidant and a Functionally Pleiotropic Molecule: Synthesis, Metabolism and Activities in Organisms"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Bioorganic Chemistry".

Deadline for manuscript submissions: 30 January 2018

Special Issue Editor

Guest Editor
Dr. Dun-Xian Tan

Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
Website | E-Mail
Phone: 210-567-2550
Interests: melatonin biology; antioxidant; antioxidative stress; melatonin systhesis and metabolism; mitochondria; chloroplast; plants

Special Issue Information

Dear Colleagues,

Melatonin is a phylogenetically ancient molecule. It is present in almost all organisms, from bacteria to humans. It is a functionally pleiotropic molecule and it is functional as an antioxidant, cancer inhibitor, inflammatory suppressor, immuno-enhancement agent, plant growth hormone and circadian rhythm regulator. It has been hypothesized that all these functions of melatonin was evolved from its antioxidant activity. Recently, the research focus was given to the synthesis and metabolism of this indolamine in different species, particulaly in plants and microorganisms and also its utilities in human health, agriculture and animal husbandry.

This Special Issue covers all aspects of pineal, melatonin and melatonin derivatives as related to their production and molecular actions in organisms from bacteria to human, including plants. Specific interests include the ability of melatonin and its metabolites to neutralize oxygen and nitrogen based toxic reactants and to protect against the associated molecular damage. This includes physical, psychological, chemical and drug-mediated injuries in animals and environmental biotic and abiotic stress in plants and microorganisms. Additionally to be included would be research articles and reviews related to novel aspects of melatonin synthesis, metabolism and applications in a variety of fields.

Dr. Dun-Xian Tan
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • melatonin synthesis
  • melatonin metabolites
  • antioxidant
  • free radical
  • oxidative stress
  • animals
  • plants
  • microorganism

Published Papers (9 papers)

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Research

Open AccessArticle Genomic Analysis of the ASMT Gene Family in Solanum lycopersicum
Molecules 2017, 22(11), 1984; doi:10.3390/molecules22111984
Received: 30 October 2017 / Accepted: 11 November 2017 / Published: 16 November 2017
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Abstract
Acetylserotonin methyltransferase (ASMT) is the last enzyme of melatonin biosynthesis and may play a rate-limiting role in the melatonin production of plants. In this study, systematic analysis of the ASMT gene family in tomato (Solanum lycopersicum Mill) has been presented by the
[...] Read more.
Acetylserotonin methyltransferase (ASMT) is the last enzyme of melatonin biosynthesis and may play a rate-limiting role in the melatonin production of plants. In this study, systematic analysis of the ASMT gene family in tomato (Solanum lycopersicum Mill) has been presented by the integration of the structural features, phylogenetic relationships, exon/intron configuration, and expression profile during growth and development, as well as biotic stresses. The results revealed that the tomato genome encoded a minimum of 14 members, containing three probable encoded pseudogenes. Chromosome mapping indicated that the family had probably expanded via tandem duplication events. Genome-wide RNA-seq and qRT-PCR based gene expression analysis revealed that almost half of the SlASMT genes were expressed in at least one of the experimental stages studied and also showed differential accumulation. Furthermore, the tandem duplicated SlASMT genes showed differential expression levels, which indicated probable functional divergence during the course of the evolution. Finally, this study also determined that some SlASMT genes were induced by multiple pathogens. The results suggested that these genes could be involved in tomato plant response to biotic stresses. Full article
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Open AccessArticle Endotoxin-Induced Inflammation Suppresses the Effect of Melatonin on the Release of LH from the Ovine Pars Tuberalis Explants—Ex Vivo Study
Molecules 2017, 22(11), 1933; doi:10.3390/molecules22111933
Received: 18 September 2017 / Revised: 3 November 2017 / Accepted: 7 November 2017 / Published: 10 November 2017
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Abstract
The secretion of the hormone melatonin reliably reflects environmental light conditions. Among numerous actions, in seasonal breeders, melatonin may regulate the secretion of the gonadotropins acting via its corresponding receptors occurring in the Pars Tuberalis (PT). However, it was previously found
[...] Read more.
The secretion of the hormone melatonin reliably reflects environmental light conditions. Among numerous actions, in seasonal breeders, melatonin may regulate the secretion of the gonadotropins acting via its corresponding receptors occurring in the Pars Tuberalis (PT). However, it was previously found that the secretory activity of the pituitary may be dependent on the immune status of the animal. Therefore, this study was designed to determine the role of melatonin in the modulation of luteinizing hormone (LH) secretion from the PT explants collected from saline- and endotoxin-treated ewes in the follicular phase of the oestrous cycle. Twelve Blackhead ewes were sacrificed 3 h after injection with lipopolysaccharide (LPS; 400 ng/kg) or saline, and the PTs were collected. Each PT was cut into 4 explants, which were then divided into 4 groups: I, incubated with ‘pure’ medium 199; II, treated with gonadotropin-releasing hormone (GnRH) (100 pg/mL); III, treated with melatonin (10 nmol/mL); and IV, incubated with GnRH and melatonin. Melatonin reduced (p < 0.05) GnRH-induced secretion of LH only in the PT from saline-treated ewes. Explants collected from LPS-treated ewes were characterized by lower (p < 0.05) GnRH-dependent response in LH release. It was also found that inflammation reduced the gene expression of the GnRH receptor and the MT1 melatonin receptors in the PT. Therefore, it was shown that inflammation affects the melatonin action on LH secretion from the PT, which may be one of the mechanisms via which immune/inflammatory challenges disturb reproduction processes in animals. Full article
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Open AccessArticle The Regulatory Mechanism of MLT/MT1 Signaling on the Growth of Antler Mesenchymal Cells
Molecules 2017, 22(10), 1793; doi:10.3390/molecules22101793
Received: 27 September 2017 / Revised: 17 October 2017 / Accepted: 19 October 2017 / Published: 23 October 2017
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Abstract
Melatonin (MLT) plays an important role in regulating the physiological cycle of seasonal breeding animals. Melatonin receptor I (MT1) is effectively expressed in the cambium layer of deer antler. However, the function and metabolic mechanism of MLT/MT1 signaling in the mesenchymal cells of
[...] Read more.
Melatonin (MLT) plays an important role in regulating the physiological cycle of seasonal breeding animals. Melatonin receptor I (MT1) is effectively expressed in the cambium layer of deer antler. However, the function and metabolic mechanism of MLT/MT1 signaling in the mesenchymal cells of sika deer remain to be further elucidated. In this work, we detected the effects of MLT/MT1 signaling on mesenchymal cells proliferation and the interaction between MLT/MT1 and IGF1/IGF1-R signaling. The results show that (1) deer antler mesenchymal cells actually express MT1; (2) exogenous melatonin significantly promotes mesenchymal cells proliferation, while MT1 knock-down significantly impairs the positive effects of melatonin; and (3) melatonin significantly enhanced IGF1/IGF1-R signaling, as both the expression of IGF1 and IGF-1R increased, while MT1 knock-down significantly decreased IGF1-R expression and IGF1 synthesis. In summary, these data verified that MLT/MT1 signaling plays a crucial role in antler mesenchymal proliferation, which may be mediated by IGF1/IGF1-R. Full article
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Open AccessCommunication Cadmium Disrupts Subcellular Organelles, Including Chloroplasts, Resulting in Melatonin Induction in Plants
Molecules 2017, 22(10), 1791; doi:10.3390/molecules22101791
Received: 13 September 2017 / Revised: 18 October 2017 / Accepted: 21 October 2017 / Published: 23 October 2017
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Abstract
Cadmium is a well-known elicitor of melatonin synthesis in plants, including rice. However, the mechanisms by which cadmium induces melatonin induction remain elusive. To investigate whether cadmium influences physical integrities in subcellular organelles, we treated tobacco leaves with either CdCl2 or AlCl
[...] Read more.
Cadmium is a well-known elicitor of melatonin synthesis in plants, including rice. However, the mechanisms by which cadmium induces melatonin induction remain elusive. To investigate whether cadmium influences physical integrities in subcellular organelles, we treated tobacco leaves with either CdCl2 or AlCl3 and monitored the structures of subcellular organelles—such as chloroplasts, mitochondria, and the endoplasmic reticulum (ER)—using confocal microscopic analysis. Unlike AlCl3 treatment, CdCl2 (0.5 mM) treatment significantly disrupted chloroplasts, mitochondria, and ER. In theory, the disruption of chloroplasts enabled chloroplast-expressed serotonin N-acetyltransferase (SNAT) to encounter serotonin in the cytoplasm, leading to the synthesis of N-acetylserotonin followed by melatonin synthesis. In fact, the disruption of chloroplasts by cadmium, not by aluminum, gave rise to a huge induction of melatonin in rice leaves, which suggests that cadmium-treated chloroplast disruption plays an important role in inducing melatonin in plants by removing physical barriers, such as chloroplast double membranes, allowing SNAT to gain access to the serotonin substrate enriched in the cytoplasm. Full article
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Open AccessArticle Melatonin Improves the Photosynthetic Carbon Assimilation and Antioxidant Capacity in Wheat Exposed to Nano-ZnO Stress
Molecules 2017, 22(10), 1727; doi:10.3390/molecules22101727
Received: 23 September 2017 / Revised: 9 October 2017 / Accepted: 12 October 2017 / Published: 18 October 2017
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Abstract
The release of nanoparticles into the environment is inevitable, which has raised global environmental concern. Melatonin is involved in various stress responses in plants. The present study investigated the effects of melatonin on photosynthetic carbon (C) assimilation and plant growth in nano-ZnO stressed
[...] Read more.
The release of nanoparticles into the environment is inevitable, which has raised global environmental concern. Melatonin is involved in various stress responses in plants. The present study investigated the effects of melatonin on photosynthetic carbon (C) assimilation and plant growth in nano-ZnO stressed plants. It was found that melatonin improved the photosynthetic C assimilation in nano-ZnO stressed wheat plants, mainly due to the enhanced photosynthetic energy transport efficiency, higher chlorophyll concentration and higher activities of Rubisco and ATPases. In addition, melatonin enhanced the activities of antioxidant enzymes to protect the photosynthetic electron transport system in wheat leaves against the oxidative burst caused by nano-ZnO stress. These results suggest that melatonin could improve the tolerance of wheat plants to nano-ZnO stress. Full article
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Open AccessArticle Melatonin Treatment Reduces Oxidative Damage and Normalizes Plasma Pro-Inflammatory Cytokines in Patients Suffering from Charcot-Marie-Tooth Neuropathy: A Pilot Study in Three Children
Molecules 2017, 22(10), 1728; doi:10.3390/molecules22101728
Received: 26 September 2017 / Revised: 10 October 2017 / Accepted: 12 October 2017 / Published: 14 October 2017
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Abstract
Charcot-Marie-Tooth neuropathy (CMT) is a motor and sensory neuropathy comprising a heterogeneous group of inherited diseases. The CMT1A phenotype is predominant in the 70% of CMT patients, with nerve conduction velocity reduction and hypertrophic demyelination. These patients have elevated oxidative stress and chronic
[...] Read more.
Charcot-Marie-Tooth neuropathy (CMT) is a motor and sensory neuropathy comprising a heterogeneous group of inherited diseases. The CMT1A phenotype is predominant in the 70% of CMT patients, with nerve conduction velocity reduction and hypertrophic demyelination. These patients have elevated oxidative stress and chronic inflammation. Currently, there is no effective cure for CMT; herein, we investigated whether melatonin treatment may reduce the inflammatory and oxidative damage in CMT1A patients. Three patients, aged 8–10 years, were treated with melatonin (60 mg at 21:00 h plus 10 mg at 09:00 h), and plasma levels of lipid peroxidation (LPO), nitrites (NOx), IL-1β, IL-2, IL-6, TNF-α, INF-γ, oxidized to reduced glutathione (GSSG/GSH) ratio, and the activities of superoxide dismutase (SOD), glutathione-S transferase (GST), glutathione peroxidase (GPx), and reductase (GRd), were determined in erythrocytes at 3 and 6 months of treatment. Healthy age- and sex-matched subjects were used as controls. The results showed increased activities of SOD, GST, GPx, and GRd in CMT1A patients, which were reduced at 3 and 6 months of treatment. The GSSG/GSH ratio significantly increased in the patients, returning to control values after melatonin treatment. The inflammatory process was confirmed by the elevation of all proinflammatory cytokines measured, which were also normalized by melatonin. LPO and NOx, which also were elevated in the patients, were normalized by melatonin. The results document beneficial effects of the use of melatonin in CMT1A patients to reduce the hyperoxidative and inflammatory condition, which may correlate with a reduction of the degenerative process. Full article
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Open AccessArticle A Comparative Genomic and Transcriptomic Survey Provides Novel Insights into N-Acetylserotonin Methyltransferase (ASMT) in Fish
Molecules 2017, 22(10), 1653; doi:10.3390/molecules22101653
Received: 14 September 2017 / Revised: 29 September 2017 / Accepted: 30 September 2017 / Published: 2 October 2017
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Abstract
Melatonin is a multifunctional bioactive molecule that plays comprehensive physiological roles in all living organisms. N-acetylserotonin methyltransferase (ASMT, also known as hydroxyindole O-methyltransferase or HIOMT) is the final enzyme for biosynthesis of melatonin. Here, we performed a comparative genomic and transcriptomic
[...] Read more.
Melatonin is a multifunctional bioactive molecule that plays comprehensive physiological roles in all living organisms. N-acetylserotonin methyltransferase (ASMT, also known as hydroxyindole O-methyltransferase or HIOMT) is the final enzyme for biosynthesis of melatonin. Here, we performed a comparative genomic and transcriptomic survey to explore the ASMT family in fish. Two ASMT isotypes (ASMT1 and ASMT2) and a new ASMT-like (ASMTL) are all extracted from teleost genomes on the basis of phylogenetic and synteny analyses. We confirmed that C-terminal of the ASMTL proteins (ASMTL-ASMT) is homology to the full length of ASMT1 and ASMT2. Our results also demonstrate that the two ASMT isotypes and their distribution in teleosts seem to be the result of combinations of whole-genome duplication (WGD) and gene loss. Differences were also observed in tissue distribution and relative transcript abundances of ASMT1, ASMT2 and ASMTL through transcriptomic analysis. Protein sequence alignment and 3D structure prediction of ASMTs and ASMTL suggest differential roles for these ASMT genes. In summary, our current work provides novel insights into the ASMT genes in fish by combination of genomic and transcriptomic data. Full article
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Open AccessArticle Exogenous Melatonin Alleviates Alkaline Stress in Malus hupehensis Rehd. by Regulating the Biosynthesis of Polyamines
Molecules 2017, 22(9), 1542; doi:10.3390/molecules22091542
Received: 27 August 2017 / Revised: 7 September 2017 / Accepted: 11 September 2017 / Published: 13 September 2017
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Abstract
Since melatonin was identified in plants decades ago, much attention has been devoted to discovering its role in plant science. There is still a great deal to learn about the functional importance of melatonin, as well as its functional mode. In this paper,
[...] Read more.
Since melatonin was identified in plants decades ago, much attention has been devoted to discovering its role in plant science. There is still a great deal to learn about the functional importance of melatonin, as well as its functional mode. In this paper, we examine the role of melatonin treatment in the response of Malus hupehensis Rehd. to alkaline conditions. Stressed seedlings showed chlorosis and suppressed growth. However, this phenotype was ameliorated when 5 µM melatonin was added to the irrigation solution. This supplementation was also associated with a reduction in cell membrane damage and maintenance of a normal root system architecture. Fewer reactive oxygen species (ROS) were accumulated due to the enhanced scavenging activity of antioxidant enzymes superoxide dismutase, peroxidase, and catalase. In addition, alkaline-stressed seedlings that received the melatonin supplement accumulated more polyamines compared with untreated seedlings. Transcript levels of six genes involved in polyamine synthesis, including SAMDC1, -3, and -4, and SPDS1, -3, and -5, -6, were upregulated in response to melatonin application. All of these results demonstrate that melatonin has a positive function in plant tolerance to alkaline stress because it regulates enzyme activity and the biosynthesis of polyamines. Full article
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Open AccessArticle Effects of Sleep Quality on Melatonin Levels and Inflammatory Response after Major Abdominal Surgery in an Intensive Care Unit
Molecules 2017, 22(9), 1537; doi:10.3390/molecules22091537
Received: 7 August 2017 / Revised: 10 September 2017 / Accepted: 10 September 2017 / Published: 12 September 2017
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Abstract
Disruption of nocturnal sleep in an intensive care unit may remarkably affect production of melatonin, which is also known to have anti-inflammatory properties. In the present study, we aimed to investigate the effect of sleep quality on melatonin levels and inflammation after surgery.
[...] Read more.
Disruption of nocturnal sleep in an intensive care unit may remarkably affect production of melatonin, which is also known to have anti-inflammatory properties. In the present study, we aimed to investigate the effect of sleep quality on melatonin levels and inflammation after surgery. Thus, we compared the patients, who were screened in the side-rooms where the lights were dimmed and noise levels were reduced, with the patients who received usual care. Preoperative and postoperative urine 6-sulphatoxymelatonin, serum interleukin-1 (IL-1), interleukin-6 (IL-6), and c-reactive protein (CRP) levels were measured and data on sleep quality was collected using the Richards–Campbell Sleep Questionnaire. Postoperative CRP and IL-6 levels were greater in the control group than in the experimental group, whereas postoperative 24 h melatonin levels were greater than preoperative levels and the difference was steeper in the experimental group in concordance with sleep quality scores. Thus, the regulation of light and noise in ICUs may help the recovery after major surgeries in patients, potentially by increasing melatonin production, which has anti-inflammatory properties. Full article
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