Melatonin Synthesis and Function: Evolutionary History in Animals and Plants

Frontiers in Endocrinology, Journal Year: 2019, Volume and Issue: 10

Published: April 17, 2019

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

Language: Английский

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Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis

International Journal of Molecular Sciences, Journal Year: 2017, Volume and Issue: 18(4), P. 843 - 843

Published: April 17, 2017

There is highly credible evidence that melatonin mitigates cancer at the initiation, progression and metastasis phases. In many cases, molecular mechanisms underpinning these inhibitory actions have been proposed. What rather perplexing, however, large number of processes by which reportedly restrains development growth. These diverse suggest what being observed are merely epiphenomena an underlying more fundamental action remains to be disclosed. Some arresting on clearly membrane receptor-mediated while others receptor-independent involve direct intracellular this ubiquitously-distributed molecule. While emphasis melatonin/cancer research has role indoleamine in restraining breast cancer, changing quickly with types having shown susceptible inhibition melatonin. several facets could immediate applications clinical level. Many studies melatonin's co-administration improves sensitivity cancers conventional drugs. Even important findings renders previously totally resistant treatment sensitive same therapies. Melatonin also inhibits associated limiting entrance cells into vascular system preventing them from establishing secondary growths distant sites. This particular importance since often significantly contributes death patient. Another area deserves additional consideration related capacity reducing toxic consequences anti-cancer drugs increasing their efficacy. Although information available for than a decade, it not adequately exploited if only beneficial patients its ability attenuate acute long-term drug toxicity, should used improve physical wellbeing patients. The experimental findings, advantages using as co-treatment therapies would far exceed improvements

Language: Английский

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Melatonin prevents endothelial cell pyroptosis via regulation of long noncoding RNA MEG3/miR‐223/NLRP3 axis

Journal of Pineal Research, Journal Year: 2017, Volume and Issue: 64(2)

Published: Oct. 11, 2017

Atherosclerosis (AS) is an inflammatory disease linked to endothelial dysfunction. Melatonin reported possess substantial anti-inflammatory properties, which has proven be effective in AS. Emerging literature suggests that pyroptosis plays a critical role during AS progression. However, whether contributes dysfunction and the underlying molecular mechanisms remained unexploited. This study was designed investigate antipyroptotic effects of melatonin atherosclerotic endothelium elucidate potential mechanisms. In this study, high-fat diet (HFD)-treated ApoE-/- mice were used as animal model. We found intragastric administration for 12 weeks markedly reduced plaque aorta. Meanwhile, also attenuated expression pyroptosis-related genes, including NLRP3, ASC, cleaved caspase1, NF-κB/GSDMD, GSDMD N-termini, IL-1β, IL-18 aortic melatonin-treated animals. Consistent observed ox-LDL-treated human cells (HAECs). lncRNA MEG3 enhanced HAECs. Moreover, acted endogenous sponge by sequence complementarity suppress function miR-223 increase NLRP3 enhance cell pyroptosis. Furthermore, knockdown blocked actions Together, our results suggest prevents via MEG3/miR-223/NLRP3 axis atherosclerosis, therefore, replacement might considered new strategy protecting against pyroptosis, thereby treatment atherosclerosis associated with

Language: Английский

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Mitochondria: Central Organelles for Melatonin′s Antioxidant and Anti-Aging Actions

Molecules, Journal Year: 2018, Volume and Issue: 23(2), P. 509 - 509

Published: Feb. 24, 2018

Melatonin, along with its metabolites, have long been known to significantly reduce the oxidative stress burden of aging cells or exposed toxins. Oxidative damage is a result free radicals produced in cells, especially mitochondria. When measured, melatonin, potent antioxidant, was found be higher concentrations mitochondria than other organelles subcellular locations. Recent evidence indicates that mitochondrial membranes possess transporters aid rapid uptake melatonin by these against gradient. Moreover, we predicted several years ago that, because their origin from melatonin-producing bacteria, likely also synthesize melatonin. Data accumulated within last year supports this prediction. A high content would fortuitous, since produce an abundance radicals. Thus, optimally positioned scavenge and degree damage. In light “free radical theory aging”, including all iterations, levels expected protect age-related organismal decline. Also, there are many age-associated diseases have, as contributing factor, These multiple may deferred onset progression if can maintained into advanced age.

Language: Английский

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Melatonin and its metabolites vs oxidative stress: From individual actions to collective protection

Journal of Pineal Research, Journal Year: 2018, Volume and Issue: 65(1)

Published: June 11, 2018

Abstract Oxidative stress (OS) represents a threat to the chemical integrity of biomolecules including lipids, proteins, and DNA. The associated molecular damage frequently results in serious health issues, which justifies our concern about this phenomenon. In addition enzymatic defense mechanisms, there are compounds (usually referred as antioxidants) that offer protection against oxidative events. Among them, melatonin its metabolites constitute particularly efficient family. They OS individual entities through wide variety mechanisms electron transfer, hydrogen radical adduct formation, metal chelation, by repairing biological targets. fact, many them can be classified multipurpose antioxidants. However, what seems unique melatonin's family is their collective effects. Because members metabolically related, most expected present living organisms wherever produced. Therefore, exerted may viewed result combined antioxidant effects parent molecule metabolites. Melatonin's rather exceptional regard, offering versatile OS. It certainly one best nature's defenses damage.

Language: Английский

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Melatonin: A Cutaneous Perspective on its Production, Metabolism, and Functions

Journal of Investigative Dermatology, Journal Year: 2018, Volume and Issue: 138(3), P. 490 - 499

Published: Feb. 7, 2018

Language: Английский

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Steps in metastasis: an updated review

Medical Oncology, Journal Year: 2021, Volume and Issue: 38(1)

Published: Jan. 1, 2021

Language: Английский

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Melatonin alleviates intervertebral disc degeneration by disrupting the IL-1β/NF-κB-NLRP3 inflammasome positive feedback loop

Bone Research, Journal Year: 2020, Volume and Issue: 8(1)

Published: Feb. 18, 2020

Abstract The inflammatory response is induced by the overexpression of cytokines, mainly interleukin (IL)-1β, and one main causes intervertebral disc degeneration (IVDD). NLR pyrin domain containing 3 (NLRP3) inflammasome activation an important source IL-1β. As anti-inflammatory neuroendocrine hormone, melatonin plays various roles in different pathophysiological conditions. However, its IVDD are still not well understood require more examination. First, we demonstrated that delayed progression relieved IVDD-related low back pain a rat needle puncture model; moreover, NLRP3 (NLRP3, p20, IL-1β levels) was significantly upregulated severely degenerated human discs model. Subsequently, IL-1β/NF-κB-NLRP3 positive feedback loop found nucleus pulposus (NP) cells were treated with In these cells, expression p20 increased, NF-κB signaling involved this regulation, mitochondrial reactive oxygen species (mtROS) production increased. Furthermore, disrupted vitro vivo. Melatonin treatment decreased NLRP3, levels inhibiting downregulating mtROS production. Finally, showed mediated disruption study, for first time promotes own upregulating activation. disrupts may be potential therapeutic agent IVDD.

Language: Английский

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Melatonin and Cancer Hallmarks

Molecules, Journal Year: 2018, Volume and Issue: 23(3), P. 518 - 518

Published: Feb. 26, 2018

Melatonin is a natural indoleamine produced by the pineal gland that has many functions, including regulation of circadian rhythm. Many studies have reported anticancer effect melatonin against myriad cancer types. Cancer hallmarks include sustained proliferation, evading growth suppressors, metastasis, replicative immortality, angiogenesis, resisting cell death, altered cellular energetics, and immune evasion. activity mediated interfering with various hallmarks. This review summarizes role in each hallmark. The discussed this should serve as solid foundation for researchers physicians to support basic clinical on promising agent.

Language: Английский

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Andrographolide, a diterpene lactone from Andrographis paniculata and its therapeutic promises in cancer

Cancer Letters, Journal Year: 2018, Volume and Issue: 420, P. 129 - 145

Published: Feb. 14, 2018

Language: Английский

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