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Hormone Molecular Biology and Clinical... Aug 2021Leukaemia is a haematological malignancy originated from the bone marrow. Studies have shown that shift work could disrupt the melatonin secretion and eventually... (Review)
Review
Leukaemia is a haematological malignancy originated from the bone marrow. Studies have shown that shift work could disrupt the melatonin secretion and eventually increase leukaemia incidence risk. Melatonin, a pineal hormone, has shown promising oncostatic properties on a wide range of cancers, including leukaemia. We first reviewed the relationship between shift work and the incidence rate of leukaemia and then discussed the role of melatonin receptors (MT1 and MT2) and their functions in leukaemia. Moreover, the connection between inflammation and leukaemia, and melatonin-induced anti-leukaemia mechanisms including anti-proliferation, apoptosis induction and immunomodulation are comprehensively discussed. Apart from that, the synergistic effects of melatonin with other anticancer compounds are also included. In short, this review article has compiled the evidence of anti-leukaemia properties displayed by melatonin and discuss its potential to act as adjunct for anti-leukaemia treatment. This review may serve as a reference for future studies or experimental research to explore the possibility of melatonin serving as a novel therapeutic agent for leukaemia.
Topics: Animals; Apoptosis; Cell Proliferation; Disease Management; Humans; Leukemia; Melatonin; Outcome Assessment, Health Care; Receptors, Melatonin
PubMed: 34355548
DOI: 10.1515/hmbci-2021-0009 -
American Journal of Physiology. Lung... Dec 2021Nocturnal asthma is characterized by heightened bronchial reactivity at night, and plasma melatonin concentrations are higher in patients with nocturnal asthma symptoms....
Nocturnal asthma is characterized by heightened bronchial reactivity at night, and plasma melatonin concentrations are higher in patients with nocturnal asthma symptoms. Numerous physiological effects of melatonin are mediated via its specific G protein-coupled receptors (GPCRs) named the MT receptor, which couples to both G and G proteins, and the MT receptor, which couples to G. We investigated whether melatonin receptors are expressed on airway smooth muscle; whether they regulate intracellular cyclic AMP (cAMP) and calcium concentrations ([Ca]), which modulate airway smooth muscle tone; and whether they promote airway smooth muscle cell proliferation. We detected the mRNA and protein expression of the melatonin MT but not the MT receptor in native human and guinea pig airway smooth muscle and cultured human airway smooth muscle (HASM) cells by RT-PCR, immunoblotting, and immunohistochemistry. Activation of melatonin MT receptors with either pharmacological concentrations of melatonin (10-100 µM) or the nonselective MT/MT agonist ramelteon (10 µM) significantly inhibited forskolin-stimulated cAMP accumulation in HASM cells, which was reversed by the Gα protein inhibitor pertussis toxin or knockdown of the MT receptor by its specific siRNA. Although melatonin by itself did not induce an initial [Ca] increase and airway contraction, melatonin significantly potentiated acetylcholine-stimulated [Ca] increases, stress fiber formation through the MT receptor in HASM cells, and attenuated the relaxant effect of isoproterenol in guinea pig trachea. These findings suggest that the melatonin MT receptor is expressed in ASM, and modulates airway smooth muscle tone via reduced cAMP production and increased [Ca].
Topics: Acetylcholine; Adult; Animals; Antioxidants; Colforsin; Cyclic AMP; Guinea Pigs; Humans; Male; Melatonin; Middle Aged; Muscle Contraction; Muscle Relaxation; Myocytes, Smooth Muscle; Receptor, Melatonin, MT2; Respiratory System; Vasodilator Agents
PubMed: 34612067
DOI: 10.1152/ajplung.00273.2021 -
Journal of the Formosan Medical... Aug 2019Melatonin (N-acetyl-5-methoxytryptamine), secreted by the pineal gland is known to perform multiple functions including, antioxidant, anti-hypertensive, anti-cancerous,... (Review)
Review
Melatonin (N-acetyl-5-methoxytryptamine), secreted by the pineal gland is known to perform multiple functions including, antioxidant, anti-hypertensive, anti-cancerous, immunomodulatory, sedative and tranquilizing functions. Melatonin is also known to be involved in the regulation of body mass index, control the gastrointestinal system and play an important role in cardioprotection, thermoregulation, and reproduction. Recently, several studies have reported the efficacy of Melatonin in treating various pain syndromes. The current paper reviews the studies on Melatonin and its analogs, particularly in Neuropathic pain. Here, we first briefly summarized research in preclinical studies showing the possible mechanisms through which Melatonin and its analogs induce analgesia in Neuropathic pain. Second, we reviewed research indicating the role of Melatonin in attenuating analgesic tolerance. Finally, we discussed the recent studies that reported novel Melatonin agonists, which were proven to be effective in treating Neuropathic pain.
Topics: Analgesics; Animals; Drug Evaluation, Preclinical; Humans; Melatonin; Neuralgia; Receptor, Melatonin, MT2
PubMed: 30316678
DOI: 10.1016/j.jfma.2018.09.017 -
The Plant Journal : For Cell and... Jan 2021Melatonin is a multifunctional biomolecule found in both animals and plants. In this review, the biosynthesis, levels, signaling, and possible roles of melatonin and its... (Review)
Review
Melatonin is a multifunctional biomolecule found in both animals and plants. In this review, the biosynthesis, levels, signaling, and possible roles of melatonin and its metabolites in plants is summarized. Tryptamine 5-hydroxylase (T5H), which catalyzes the conversion of tryptamine into serotonin, has been proposed as a target to create a melatonin knockout mutant presenting a lesion-mimic phenotype in rice. With a reduced anabolic capacity for melatonin biosynthesis and an increased catabolic capacity for melatonin metabolism, all plants generally maintain low melatonin levels. Some plants, including Arabidopsis and Nicotiana tabacum (tobacco), do not possess tryptophan decarboxylase (TDC), the first committed step enzyme required for melatonin biosynthesis. Major melatonin metabolites include cyclic 3-hydroxymelatonin (3-OHM) and 2-hydroxymelatonin (2-OHM). Other melatonin metabolites such as N -acetyl-N -formyl-5-methoxykynuramine (AFMK), N-acetyl-5-methoxykynuramine (AMK) and 5-methoxytryptamine (5-MT) are also produced when melatonin is applied to Oryza sativa (rice). The signaling pathways of melatonin and its metabolites act via the mitogen-activated protein kinase (MAPK) cascade, possibly with Cand2 acting as a melatonin receptor, although the integrity of Cand2 remains controversial. Melatonin mediates many important functions in growth stimulation and stress tolerance through its potent antioxidant activity and function in activating the MAPK cascade. The concentration distribution of melatonin metabolites appears to be species specific because corresponding enzymes such as M2H, M3H, catalases, indoleamine 2,3-dioxygenase (IDO) and N-acetylserotonin deacetylase (ASDAC) are differentially expressed among plant species and even among different tissues within species. Differential levels of melatonin and its metabolites can lead to differential physiological effects among plants when melatonin is either applied exogenously or overproduced through ectopic overexpression.
Topics: Genes, Plant; Melatonin; Metabolic Networks and Pathways; Plant Growth Regulators; Plant Physiological Phenomena; Plants; Receptors, Melatonin; Signal Transduction
PubMed: 32645752
DOI: 10.1111/tpj.14915 -
Frontiers in Bioscience (Landmark... Jun 2023The development of assisted reproductive techniques has significantly improved fertility chances in many women, but recurrent implantation failure (RIF) and miscarriages...
BACKGROUND
The development of assisted reproductive techniques has significantly improved fertility chances in many women, but recurrent implantation failure (RIF) and miscarriages (RM) might preclude successful pregnancy. Alterations in the intrinsic secretory patterns of melatonin and cortisol influence reproduction in humans, and imperfection of receptor - dependent signaling may additionally compromise the hormonal effects. Therefore, the present study aims to investigate the influence of certain melatonin and cortisol receptor polymorphisms in infertile women.
METHODS
A total of 111 female infertile patients suffering from implantation failure and/or miscarriages were genotyped for rs1562444, rs10830962, rs41423247, and ER22/23EK variants. Additionally, 106 female volunteers were genotyped for the same polymorphisms.
RESULTS
The allele and genotype distribution of the investigated polymorphisms did not differ between infertile women and the control group. Significantly more women with history of RIF have rs1562444 G-allele-containing genotypes in comparison to AA carriers (19.3% vs. 3.6%, = 0.004). The minor allele of the ER22/23EK variant was more frequent in infertile patients with three or more unsuccessful implantation attempts than in other women (12.5% vs. 2.4%, = 0.025).
CONCLUSIONS
Melatonin receptor 1B polymorphisms might affect embryo implantation and early pregnancy loss, while their influence on late pregnancy complications needs further evaluation. The possible association between the cortisol receptor ER22/23EK variant and recurrent implantation failure might help to differentiate women who could benefit from corticosteroid treatment.
Topics: Female; Humans; Pregnancy; Abortion, Spontaneous; Hydrocortisone; Infertility, Female; Melatonin; Receptors, Melatonin; Receptors, Steroid
PubMed: 37395040
DOI: 10.31083/j.fbl2806122 -
Archives of Medical Research Jul 2021In patients with Bipolar-I Disorder (BD-I), circadian rhythm and sleep disorders are frequently observed. Melatonin is a main regulatory hormone for the circadian...
BACKGROUND AND AIM
In patients with Bipolar-I Disorder (BD-I), circadian rhythm and sleep disorders are frequently observed. Melatonin is a main regulatory hormone for the circadian rhythm. Certain studies have shown the relationship of melatonin receptor gene polymorphism with psychiatric diseases. In this study, it was aimed to investigate the relationship between BD-I and -184T>C (rs2119882) polymorphism in melatonin receptor 1A (MTNR1A) gene and -1193C>T (rs4753426) polymorphism in melatonin receptor 1B (MTNR1B) gene.
METHODS
The study included 108 patients diagnosed with BD-I and 95 healthy people as the control group. Real-time PCR (RT-PCR) method was used to evaluate the polymorphism of MTNR1A gene-184T>C. Genotyping of MTNR1B gene-1193C>T polymorphism was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
RESULTS
In terms of MTNR1B gene-1193C>T polymorphism, homozygous CC genotype was found to be increased in BD-I patient group compared to the control group (p <0.05). Similarly, a statistically significant difference was found between the patients and the control group in terms of allele frequencies too (p <0.05). However, no relation between BD-I and MTNR1A gene-184T>C polymorphism was found (p >0.05).
CONCLUSION
The results of the study revealed that MTNR1B gene-1193C>T polymorphism may play a role in BD-I genetic etiology and may be among the causes of sleep disorder and circadian rhythm disorder seen in these patients.
Topics: Bipolar Disorder; Gene Frequency; Genotype; Humans; Melatonin; Polymorphism, Single Nucleotide; Receptors, Melatonin
PubMed: 33546869
DOI: 10.1016/j.arcmed.2021.01.002 -
European Journal of Pharmacology Mar 2024Hepatic fibrosis, when left untreated, causes serious health problems that progress to cirrhosis and, in some cases, liver cancer. Activation of hepatic stellate cells...
Hepatic fibrosis, when left untreated, causes serious health problems that progress to cirrhosis and, in some cases, liver cancer. Activation of hepatic stellate cells may be a key characteristic in the development of hepatic fibrosis. Melatonin, a pineal hormone, exerts anti-fibrotic effects; however, the exact mechanisms remain unclear. In this study, the beneficial effects of melatonin against hepatic fibrosis and the underlying mechanisms were investigated using the human hepatic stellate cell line, LX-2, and in vivo murine animal models. The results showed that melatonin suppressed the expression of transforming growth factor (TGF)-β1-induced fibrosis markers and production of reactive oxygen species in LX-2 cells. Either 4-phenyl-2-propionamidotetralin, a melatonin receptor 2 selective antagonist, or melatonin receptor 2 small interfering RNA abolished the suppressive effects of melatonin, suggesting the involvement of melatonin receptor 2 in melatonin-induced anti-fibrotic and anti-oxidative actions. Melatonin increased the expression of the brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (BMAL1), a positive circadian clock gene. BMAL1 knockdown reduced the anti-fibrotic and anti-oxidative effects of melatonin, demonstrating the protective effects of melatonin against TGF-β1-induced hepatic stellate cell activation by exhibiting melatonin receptor 2-BMAL1-anti-oxidative effects. In high-fat diet-induced and carbon tetrachloride-induced hepatic fibrosis models, oral melatonin administration decreased the expression of hepatic fibrosis markers and increased the expression of messenger RNA and levels of proteins of BMAL1 and melatonin receptor 2. Thus, melatonin exerted protective effects against hepatic fibrosis through melatonin receptor 2 activation, followed by an upregulation of the BMAL1-anti-oxidative enzyme pathways.
Topics: Animals; Humans; Mice; ARNTL Transcription Factors; Carbon Tetrachloride; Hepatic Stellate Cells; Liver; Liver Cirrhosis; Melatonin; Receptors, Melatonin; Signal Transduction; Transforming Growth Factor beta1; Up-Regulation
PubMed: 38246330
DOI: 10.1016/j.ejphar.2024.176337 -
Medicinal Research Reviews Nov 2019Within the last few decades, melatonin has increasingly emerged in clinical oncology as a naturally occurring bioactive molecule with substantial anticancer properties... (Review)
Review
Within the last few decades, melatonin has increasingly emerged in clinical oncology as a naturally occurring bioactive molecule with substantial anticancer properties and a pharmacological profile optimal for joining the currently available pharmacopeia. In addition, extensive experimental data shows that this chronobiotic agent exerts oncostatic effects throughout all stages of tumor growth, from initial cell transformation to mitigation of malignant progression and metastasis; additionally, melatonin alleviates the side effects and improves the welfare of radio/chemotherapy-treated patients. Thus, the support of clinicians and oncologists for the use of melatonin in both the treatment and proactive prevention of cancer is gaining strength. Because of its epidemiological importance and symptomatic debut in advanced stages of difficult clinical management, colorectal cancer (CRC) is a preferential target for testing new therapies. In this regard, the development of effective forms of clinical intervention for the improvement of CRC outcome, specifically metastatic CRC, is urgent. At the same time, the need to reduce the costs of conventional anti-CRC therapy results is also imperative. In light of this status quo, the therapeutic potential of melatonin, and the direct and indirect critical processes of CRC malignancy it modulates, have aroused much interest. To illuminate the imminent future on CRC research, we focused our attention on the molecular mechanisms underlying the multiple oncostatic actions displayed by melatonin in the onset and evolution of CRC and summarized epidemiological evidence, as well as in vitro, in vivo and clinical findings that support the broadly protective potential demonstrated by melatonin.
Topics: Animals; Colorectal Neoplasms; Disease Progression; Epigenesis, Genetic; Humans; Melatonin; Neoplastic Stem Cells; Receptors, Melatonin
PubMed: 30950095
DOI: 10.1002/med.21582 -
Neuropsychopharmacology : Official... Jan 2020Alterations in sleep are extremely common in patients with neuropsychiatric illness. In addition, sleep disorders such as insomnia, obstructive sleep apnea, rapid eye... (Review)
Review
Alterations in sleep are extremely common in patients with neuropsychiatric illness. In addition, sleep disorders such as insomnia, obstructive sleep apnea, rapid eye movement sleep behavior disorder, and circadian rhythm disorders commonly occur at a rate greater than the general population in neuropsychiatric conditions. Historically, sleep problems have been viewed as symptoms of associated neuropsychiatric disorders. However, there is increasing evidence suggesting a complex inter-relationship with possible bidirectional causality. The inter-relatedness of these conditions represents an opportunity for understanding mechanisms and improving clinical treatment. To the extent that sleep problems affect neuropsychiatric conditions, it may be possible to address sleep problems and have a positive impact on the course of neuropsychiatric illnesses. Further, some treatments for sleep disorders have direct effects on neuropsychiatric illnesses that may be unrelated to their effects on sleep disorders. Similarly, neuropsychiatric conditions and their treatments can affect sleep and sleep disorders. This article reviews available evidence on the effects of therapies for sleep disorders on neuropsychiatric conditions and also secondarily considers the impacts of therapies for neuropsychiatric conditions on sleep. Primary goals of this review are to identify gaps in current research, to determine the extent to which the cross-therapeutic effects of these treatments help to elucidate therapeutic or pathological mechanisms, and to assist clinicians in optimizing therapeutic choice in patients with sleep disorders and neuropsychiatric conditions.
Topics: Antidepressive Agents; Antipsychotic Agents; Humans; Mental Disorders; Receptors, Melatonin; Sleep Wake Disorders
PubMed: 31376815
DOI: 10.1038/s41386-019-0474-9 -
Cell Chemical Biology Aug 2023The presence of signaling-competent G protein-coupled receptors in intracellular compartments is increasingly recognized. Recently, the presence of G protein-coupled...
The presence of signaling-competent G protein-coupled receptors in intracellular compartments is increasingly recognized. Recently, the presence of G protein-coupled melatonin MT receptors in mitochondria has been revealed, in addition to the plasma membrane. Melatonin is highly cell permeant, activating plasma membrane and mitochondrial receptors equally. Here, we present MCS-1145, a melatonin derivative bearing a triphenylphosphonium cation for specific mitochondrial targeting and a photocleavable o-nitrobenzyl group releasing melatonin upon illumination. MCS-1145 displayed low affinity for MT and MT but spontaneously accumulated in mitochondria, where it was resistant to washout. Uncaged MCS-1145 and exogenous melatonin recruited β-arrestin 2 to MT in mitochondria and inhibited oxygen consumption in mitochondria isolated from HEK293 cells only when expressing MT and from mouse cerebellum of WT mice but not from MT-knockout mice. Overall, we developed the first mitochondria-targeted photoactivatable melatonin ligand and demonstrate that melatonin inhibits mitochondrial respiration through mitochondrial MT receptors.
Topics: Animals; Humans; Mice; Receptor, Melatonin, MT1; Melatonin; HEK293 Cells; Receptors, G-Protein-Coupled; Mitochondria; Respiration
PubMed: 37572668
DOI: 10.1016/j.chembiol.2023.07.009