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| N-Acetylserotonin (NAS), also known as normelatonin, is a naturally occurring chemical intermediate in the endogenous production of melatonin from serotonin. It also has biological activity in its own right, including acting as a melatonin receptor agonist, an agonist of the TrkB, and having antioxidant effects. |
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Read full article at Wikipedia
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| InChI=1S/C12H14N2O2/c1-8(15)13-5-4-9-7-14-12-3-2-10(16)6-11(9)12/h2-3,6-7,14,16H,4-5H2,1H3,(H,13,15) |
| MVAWJSIDNICKHF-UHFFFAOYSA-N |
| C1=CC(=CC=2C(=CNC12)CCNC(C)=O)O |
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Mus musculus
(NCBI:txid10090)
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Source: BioModels - MODEL1507180067
See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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See:
DOI
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antioxidant
A substance that opposes oxidation or inhibits reactions brought about by dioxygen or peroxides.
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human metabolite
Any mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
mouse metabolite
Any mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
tropomyosin-related kinase B receptor agonist
An agonist that binds to and deactivates the tropomyosin-related kinase B (TrkB) receptor, the main signaling receptor of the neurotrophin brain-derived neurotrophic factor (BDNF).
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View more via ChEBI Ontology
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N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]acetamide
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N-(2-(5-Hydroxy-1H-indol-3-yl)ethyl)acetamide
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ChemIDplus
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N-Acetyl-5-hydroxytryptamine
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KEGG COMPOUND
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N-Acetylserotonin
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KEGG COMPOUND
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N-acetylserotonin
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UniProt
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1210-83-9
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CAS Registry Number
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KEGG COMPOUND
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1210-83-9
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CAS Registry Number
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ChemIDplus
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479159
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Reaxys Registry Number
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Reaxys
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Ben Shahar Y, Sukhotnik I, Bitterman N, Pollak Y, Bejar J, Chepurov D, Coran A, Bitterman A (2016)
Effect of N-Acetylserotonin on Intestinal Recovery Following Intestinal Ischemia-Reperfusion Injury in a Rat.
European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie 26, 47-53 [PubMed:26378484]
[show Abstract]
ObjectiveN-acetylserotonin (NAS) is a naturally occurring chemical intermediate in the biosynthesis of melatonin. Extensive studies in various experimental models have established that treatment with NAS significantly protects heart and kidney injury from ischemia-reperfusion (IR). The purpose of the present study was to examine the effect of NAS on intestinal recovery and enterocyte turnover after intestinal IR injury in rats.MethodsMale Sprague-Dawley rats were divided into four experimental groups: (1) Sham rats underwent laparotomy, (2) sham-NAS rats underwent laparotomy and were treated with intraperitoneal (IP) NAS (20 mg/kg); (3) IR rats underwent occlusion of both superior mesenteric artery and portal vein for 30 minutes, followed by 48 hours of reperfusion, and (4) IR-NAS rats underwent IR and were treated with IP NAS (20 mg/kg) immediately before abdominal closure. Intestinal structural changes, Park injury score, enterocyte proliferation, and enterocyte apoptosis were determined 24 hours following IR. The expression of Bax, Bcl-2, p-ERK, and caspase-3 in the intestinal mucosa was determined using real-time polymerase chain reaction, Western blot, and immunohistochemistry. A nonparametric Kruskal-Wallis analysis of variance test was used for statistical analysis with p less than 0.05 considered statistically significant.ResultsTreatment with NAS resulted in a significant increase in mucosal weight in jejunum and ileum, villus height in the ileum, and crypt depth in jejunum and ileum compared with IR animals. IR-NAS rats also had a significantly proliferation rates as well as a lower apoptotic index in jejunum and ileum which was accompanied by higher Bcl-2 levels compared with IR animals.ConclusionsTreatment with NAS prevents gut mucosal damage and inhibits programmed cell death following intestinal IR in a rat. | Wen J, Ariyannur PS, Ribeiro R, Tanaka M, Moffett JR, Kirmani BF, Namboodiri AM, Zhang Y (2016)
Efficacy of N-Acetylserotonin and Melatonin in the EAE Model of Multiple Sclerosis.
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 11, 763-773 [PubMed:27562847]
[show Abstract]
Melatonin and N-acetylserotonin (NAS) are tryptophan metabolites that have potent anti-oxidant, anti-inflammatory and neuroprotective properties in several animal models of neurological injury and disease including multiple sclerosis (MS). The therapeutic effect of NAS has not been reported previously in experimental autoimmune encephalomyelitis (EAE), a commonly used animal model of MS. Using a MOG-peptide induced EAE mouse model we examined the effects of melatonin and NAS on clinical score, inflammatory markers, free radical generation, and sparing of axons, oligodendrocytes and myelin. We found that NAS and melatonin reduced clinical scores when administered prior to or after symptom onset. This effect was more pronounced when melatonin and NAS were administrated prior to symptom onset whereby the appearance of motor symptoms was significantly delayed. Activated microglia and CD4+ T-cells were increased in the white matter of untreated EAE mice, with a return to near control levels after melatonin or NAS treatment. The expression of the NADPH oxidase component p67phox and inducible nitric oxide synthase (iNOS) was increased in the EAE mice as compared with controls, and both drug treated groups had significant reductions in their expression. Melatonin and NAS treatment significantly reduced the loss of mature oligodendrocytes, demyelination and axonal injury. Both compounds also significantly attenuated iNOS induction and reactive oxygen species (ROS) generation in lipopolysaccharide-activated microglia in culture. Our results show for the first time the therapeutic effects of NAS and confirm previous reports on the effectiveness of melatonin in the EAE model of MS. | Anderson G, Rodriguez M (2015)
Multiple sclerosis: the role of melatonin and N-acetylserotonin.
Multiple sclerosis and related disorders 4, 112-123 [PubMed:25787187]
[show Abstract]
Multiple sclerosis (MS) is an immune mediated disorder that is under intensive investigation in an attempt to improve on available treatments. Many of the changes occurring in MS, including increased mitochondrial dysfunction, pain reporting and depression may be partly mediated by increased indoleamine 2,3-dioxygenase, which drives tryptophan to the production of neuroregulatory tryptophan catabolites and away from serotonin, N-acetylserotonin and melatonin production. The consequences of decreased melatonin have classically been attributed to circadian changes following its release from the pineal gland. However, recent data shows that melatonin may be produced by all mitochondria containing cells to some degree, including astrocytes and immune cells, thereby providing another important MS treatment target. As well as being a powerful antioxidant, anti-inflammatory and antinociceptive, melatonin improves mitochondrial functioning, partly via increased oxidative phosphorylation. Melatonin also inhibits demyelination and increases remyelination, suggesting that its local regulation in white matter astrocytes by serotonin availability and apolipoprotein E4, among other potential factors, will be important in the etiology, course and treatment of MS. Here we review the role of local melatonin and its precursors, N-acetylserotonin and serotonin, in MS. | Álvarez-Diduk R, Galano A, Tan DX, Reiter RJ (2015)
N-Acetylserotonin and 6-Hydroxymelatonin against Oxidative Stress: Implications for the Overall Protection Exerted by Melatonin.
The journal of physical chemistry. B 119, 8535-8543 [PubMed:26079042]
[show Abstract]
The protection exerted by N-acetylserotonin (NAS) and 6-hydroxymelatonin (6OHM) against oxidative stress was investigated using the density functional theory. It was found that these compounds are better peroxyl radical scavengers than melatonin itself, Trolox, caffeine, or genistein both in lipid and aqueous solutions. The related kinetic data is provided for the first time. The solvent polarity influences not only the absolute reactivity of NAS and 6OHM toward peroxyl radicals, but also their relative scavenging activity. In addition, they both fully inhibit the oxidative effects of copper-ascorbate mixtures, and (•)OH production via the Haber-Weiss reaction, albeit the effects on the later are only partial. On the basis of comparisons with other melatonin-related compounds, it is proposed that the role of NAS and 6OHM on the overall protection exerted by melatonin against oxidative stress is mainly related to their free radical scavenging activities. Moreover, they increase such protection. The role of the phenol moiety on such activity is demonstrated. | Zhou H, Wang J, Jiang J, Stavrovskaya IG, Li M, Li W, Wu Q, Zhang X, Luo C, Zhou S, Sirianni AC, Sarkar S, Kristal BS, Friedlander RM, Wang X (2014)
N-acetyl-serotonin offers neuroprotection through inhibiting mitochondrial death pathways and autophagic activation in experimental models of ischemic injury.
The Journal of neuroscience : the official journal of the Society for Neuroscience 34, 2967-2978 [PubMed:24553937]
[show Abstract]
N-acetylserotonin (NAS) is an immediate precursor of melatonin, which we have reported is neuroprotective against ischemic injury. Here we test whether NAS is a potential neuroprotective agent in experimental models of ischemic injury. We demonstrate that NAS inhibits cell death induced by oxygen-glucose deprivation or H2O2 in primary cerebrocortical neurons and primary hippocampal neurons in vitro, and organotypic hippocampal slice cultures ex vivo and reduces hypoxia/ischemia injury in the middle cerebral artery occlusion mouse model of cerebral ischemia in vivo. We find that NAS is neuroprotective by inhibiting the mitochondrial cell death pathway and the autophagic cell death pathway. The neuroprotective effects of NAS may result from the influence of mitochondrial permeability transition pore opening, mitochondrial fragmentation, and inhibition of the subsequent release of apoptogenic factors cytochrome c, Smac, and apoptosis-inducing factor from mitochondria to cytoplasm, and activation of caspase-3, -9, as well as the suppression of the activation of autophagy under stress conditions by increasing LC3-II and Beclin-1 levels and decreasing p62 level. However, NAS, unlike melatonin, does not provide neuroprotection through the activation of melatonin receptor 1A. We demonstrate that NAS reaches the brain subsequent to intraperitoneal injection using liquid chromatography/mass spectrometry analysis. Given that it occurs naturally and has low toxicity, NAS, like melatonin, has potential as a novel therapy for ischemic injury. | Pagan C, Delorme R, Callebert J, Goubran-Botros H, Amsellem F, Drouot X, Boudebesse C, Le Dudal K, Ngo-Nguyen N, Laouamri H, Gillberg C, Leboyer M, Bourgeron T, Launay JM (2014)
The serotonin-N-acetylserotonin-melatonin pathway as a biomarker for autism spectrum disorders.
Translational psychiatry 4, e479 [PubMed:25386956]
[show Abstract]
Elevated whole-blood serotonin and decreased plasma melatonin (a circadian synchronizer hormone that derives from serotonin) have been reported independently in patients with autism spectrum disorders (ASDs). Here, we explored, in parallel, serotonin, melatonin and the intermediate N-acetylserotonin (NAS) in a large cohort of patients with ASD and their relatives. We then investigated the clinical correlates of these biochemical parameters. Whole-blood serotonin, platelet NAS and plasma melatonin were assessed in 278 patients with ASD, their 506 first-degree relatives (129 unaffected siblings, 199 mothers and 178 fathers) and 416 sex- and age-matched controls. We confirmed the previously reported hyperserotonemia in ASD (40% (35-46%) of patients), as well as the deficit in melatonin (51% (45-57%)), taking as a threshold the 95th or 5th percentile of the control group, respectively. In addition, this study reveals an increase of NAS (47% (41-54%) of patients) in platelets, pointing to a disruption of the serotonin-NAS-melatonin pathway in ASD. Biochemical impairments were also observed in the first-degree relatives of patients. A score combining impairments of serotonin, NAS and melatonin distinguished between patients and controls with a sensitivity of 80% and a specificity of 85%. In patients the melatonin deficit was only significantly associated with insomnia. Impairments of melatonin synthesis in ASD may be linked with decreased 14-3-3 proteins. Although ASDs are highly heterogeneous, disruption of the serotonin-NAS-melatonin pathway is a very frequent trait in patients and may represent a useful biomarker for a large subgroup of individuals with ASD. | Yu S, Zheng J, Jiang Z, Shi C, Li J, Du X, Wang H, Jiang J, Wang X (2013)
Protective effect of N-acetylserotonin against acute hepatic ischemia-reperfusion injury in mice.
International journal of molecular sciences 14, 17680-17693 [PubMed:23994834]
[show Abstract]
The purpose of this study was to investigate the possible protective effect of N-acetylserotonin (NAS) against acute hepatic ischemia-reperfusion (I/R) injury in mice. Adult male mice were randomly divided into three groups: sham, I/R, and I/R + NAS. The hepatic I/R injury model was generated by clamping the hepatic artery, portal vein, and common bile duct with a microvascular bulldog clamp for 30 min, and then removing the clamp and allowing reperfusion for 6 h. Morphologic changes and hepatocyte apoptosis were evaluated by hematoxylin-eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, respectively. Activated caspase-3 expression was evaluated by immunohistochemistry and Western blot. The activation of aspartate aminotransferase (AST), malondialdehyde (MDA), and superoxide dismutase (SOD) was evaluated by enzyme-linked immunosorbent assay (ELISA). The data show that NAS rescued hepatocyte morphological damage and dysfunction, decreased the number of apoptotic hepatocytes, and reduced caspase-3 activation. Our work demonstrates that NAS ameliorates hepatic IR injury. | Roux A, Xu Y, Heilier JF, Olivier MF, Ezan E, Tabet JC, Junot C (2012)
Annotation of the human adult urinary metabolome and metabolite identification using ultra high performance liquid chromatography coupled to a linear quadrupole ion trap-Orbitrap mass spectrometer.
Analytical chemistry 84, 6429-6437 [PubMed:22770225]
[show Abstract]
Metabolic profiles of biofluids obtained by atmospheric pressure ionization mass spectrometry-based technologies contain hundreds to thousands of features, most of them remaining unknown or at least not characterized in analytical systems. We report here on the annotation of the human adult urinary metabolome and metabolite identification from electrospray ionization mass spectrometry (ESI-MS)-based metabolomics data sets. Features of biological interest were first of all annotated using the ESI-MS database of the laboratory. They were also grouped, thanks to software tools, and annotated using public databases. Metabolite identification was achieved using two complementary approaches: (i) formal identification by matching chromatographic retention times, mass spectra, and also product ion spectra (if required) of metabolites to be characterized in biological data sets to those of reference compounds and (ii) putative identification from biological data thanks to MS/MS experiments for metabolites not available in our chemical library. By these means, 384 metabolites corresponding to 1484 annotated features (659 in negative ion mode and 825 in positive ion mode) were characterized in human urine samples. Of these metabolites, 192 and 66 were formally and putatively identified, respectively, and 54 are reported in human urine for the first time. These lists of features could be used by other laboratories to annotate their ESI-MS metabolomics data sets. | Tosini G, Ye K, Iuvone PM (2012)
N-acetylserotonin: neuroprotection, neurogenesis, and the sleepy brain.
The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry 18, 645-653 [PubMed:22585341]
[show Abstract]
N-Acetylserotonin (NAS) is a naturally occurring chemical intermediate in biosynthesis of melatonin. Previous studies have shown that NAS has different brain distribution patterns from those of serotonin and melatonin, suggesting that NAS might have functions other than as a precursor or metabolite of melatonin. Indeed, several studies have now shown that NAS may play an important role in mood regulation and may have antidepressant activity. Additional studies have shown that NAS stimulates proliferation of neuroprogenitor cells and prevents some of the negative effects of sleep deprivation. It is believed that the antidepressant and neurotrophic actions of NAS are due at least in part to the capability on this molecule to activate the TrkB receptor in a brain-derived neurotrophic factor-independent manner. Emerging evidence also indicates that NAS and its derivatives have neuroprotective properties and protect retinal photoreceptor cells from light-induced degeneration. In this review, the authors discuss the literature about this exciting and underappreciated molecule. |
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