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Kyoungwhan Back - One of the best experts on this subject based on the ideXlab platform.
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Rice histone deacetylase 10 and Arabidopsis histone deacetylase 14 genes encode N-Acetylserotonin deacetylase, which catalyzes conversion of N-Acetylserotonin into serotonin, a reverse reaction for melatonin biosynthesis in plants.
2018Co-Authors: Kyung Jin Lee, Hyoung Yool Lee, Kyoungwhan BackAbstract:In plants, melatonin production is strictly regulated, unlike the production of its precursor, serotonin, which is highly inducible in response to stimuli, such as senescence and pathogen exposure. Exogenous serotonin treatment does not greatly induce the production of N-Acetylserotonin (NAS) and melatonin in plants, which suggests the possible existence of one or more regulatory genes in the pathway for the biosynthesis of melatonin from serotonin. In this report, we found that NAS was rapidly and abundantly converted into serotonin in rice seedlings, indicating the presence of an N-Acetylserotonin deacetylase (ASDAC). To clone the putative ASDAC gene, we screened 4 genes that were known as histone deacetylase (HDAC) genes, but encoded proteins targeted into chloroplasts or mitochondria rather than nuclei. Of 4 recombinant Escherichia coli strains expressing these genes, one E. coli strain expressing the rice HDAC10 gene was found to be capable of producing serotonin in response to treatment with NAS. The recombinant purified rice HDAC10 (OsHDAC10) protein exhibited ASDAC enzyme activity toward NAS, N-acetyltyramine (NAT), N-acetyltryptamine, and melatonin, with the highest ASDAC activity for NAT. In addition, its Arabidopsis ortholog, AtHDAC14, showed similar ASDAC activity to that of OsHDAC10. Both OsHDAC10 and AtHDAC14 were found to be expressed in chloroplasts. Phylogenetic analysis indicated that ASDAC homologs were present in archaea, but not in cyanobacteria, which differs from the distribution of serotonin N-acetyltransferase (SNAT). This suggests that SNAT and ASDAC may have evolved differently from ancestral eukaryotic cells.
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Cadmium Disrupts Subcellular Organelles, Including Chloroplasts, Resulting in Melatonin Induction in Plants
2017Co-Authors: Hyoung Yool Lee, Kyoungwhan BackAbstract: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
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low melatonin production by suppression of either serotonin n acetyltransferase or n acetylserotonin methyltransferase in rice causes seedling growth retardation with yield penalty abiotic stress susceptibility and enhanced coleoptile growth under anoxic conditions
2016Co-Authors: Yeong Byeon, Kyoungwhan BackAbstract:Serotonin N-acetyltransferase (SNAT) and N-Acetylserotonin methyltransferase (ASMT) are the last two key enzymes for melatonin biosynthesis in living organisms. In this study, we demonstrated that transgenic rice (Oryza sativa L.) plants, in which expression of either endogenous SNAT or ASMT was suppressed, had reduced melatonin synthesis, confirming that both SNAT and ASMT are functionally involved in melatonin synthesis. The melatonin-deficient SNAT rice had retarded seedling growth, which was partially restored by exogenous melatonin application, suggesting melatonin's role in seedling growth. In addition, the plants were more sensitive to various abiotic stresses, including salt and cold, compared with the wild type. Melatonin-deficient SNAT rice had increased coleoptile growth under anoxic conditions, indicating that melatonin also inversely regulates plant growth under anaerobic conditions with the concomitant high expression of alcohol dehydrogenase genes. Similarly, the melatonin-deficient ASMT rice exhibited accelerated senescence in detached flag leaves, as well as significantly reduced yield. These loss-of-function studies on the melatonin biosynthetic genes confirmed most previous pharmacological reports that melatonin not only promotes plant growth but also mitigates various abiotic stresses.
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chloroplastic and cytoplasmic overexpression of sheep serotonin n acetyltransferase in transgenic rice plants is associated with low melatonin production despite high enzyme activity
2015Co-Authors: Yeong Byeon, Kyoungwhan BackAbstract:: Serotonin N-acetyltransferase (SNAT), the penultimate enzyme in melatonin biosynthesis, catalyzes the conversion of serotonin into N-Acetylserotonin. Plant SNAT is localized in chloroplasts. To test SNAT localization effects on melatonin synthesis, we generated transgenic rice plants overexpressing a sheep (Ovis aries) SNAT (OaSNAT) in their chloroplasts and compared melatonin biosynthesis with that of transgenic rice plants overexpressing OaSNAT in their cytoplasm. To localize the OaSNAT in chloroplasts, we used a chloroplast targeting sequence (CTS) from tobacco protoporphyrinogen IX oxidase (PPO), which expresses in chloroplasts. The purified recombinant CTS:OaSNAT fusion protein was enzymatically functional and localized in chloroplasts as confirmed by confocal microscopic analysis. The chloroplast-targeted CTS:OaSNAT lines and cytoplasm-expressed OaSNAT lines had similarly high SNAT enzyme activities. However, after cadmium and butafenacil treatments, melatonin production in rice leaves was severalfold lower in the CTS:OaSNAT lines than in the OaSNAT lines. Notably, enhanced SNAT enzyme activity was not directly proportional to the production of N-Acetylserotonin, melatonin, or 2-hydroxymelatonin, suggesting that plant SNAT has a role in the homeostatic regulation of melatonin rather than in accelerating melatonin synthesis.
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cloning and characterization of a serotonin n acetyltransferase from a gymnosperm loblolly pine pinus taeda
2014Co-Authors: Sangkyu Park, Yeong Byeon, Young Soon Kim, Hyoung Yool Lee, Taeho Ahn, Kyoungwhan BackAbstract:Serotonin N-acetyltransferase (SNAT) is the penultimate enzyme in melatonin biosynthesis in both animals and plants. SNAT catalyzes serotonin into N-Acetylserotonin, an immediate precursor for melatonin biosynthesis by N-Acetylserotonin methyltransferase (ASMT). We cloned the SNAT gene from a gymnosperm loblolly pine (Pinus teada). The loblolly pine SNAT (PtSNAT) gene encodes 255 amino acids harboring a transit sequence with 67 amino acids and shows 67% amino acid identity with rice SNAT when comparing the mature polypeptide regions. Purified recombinant PtSNAT showed peak activity at 55°C with the K(m) (428 μM) and Vmax (3.9 nmol/min/mg protein) values. As predicted, PtSNAT localized to chloroplasts. The SNAT mRNA was constitutively expressed in all tissues, including leaf, bud, flower, and pinecone, whereas the corresponding protein was detected only in leaf. In accordance with the exclusive SNAT protein expression in leaf, melatonin was detected only in leaf at 0.45 ng per gram fresh weight. Sequence and phylogenetic analysis indicated that the gymnosperm PtSNAT had high homology with SNATs from all plant phyla (even with cyanobacteria), and formed a clade separated from the angiosperm SNATs, suggestive of direct gene transfer from cyanobacteria via endosymbiosis.
Gregory F Oxenkrug - One of the best experts on this subject based on the ideXlab platform.
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effect of methylene blue and related redox dyes on monoamine oxidase activity rat pineal content of n acetylserotonin melatonin and related indoles and righting reflex in melatonin primed frogs
2007Co-Authors: Gregory F Oxenkrug, Sergey O Sablin, Pura J RequintinaAbstract:The ability of methylene blue (MB) to inhibit the nitric oxide-induced stimulation of N-methyl-D-aspartate receptors has been suggested as a possible mechanism of MB's clinical antidepressant action. This study evaluated the alternative/additional mechanisms of the antidepressant effect of MB on biochemical and behavior levels. Selective inhibition of monoamine oxidase type A (MAO-A) is widely accepted as a major mechanism of the clinical antidepressant effect. MB and the related redox dyes toluidine blue O (TBO), thionine (TN), brilliant cresyl blue (BCB), and toluylene blue (TB) were reversible competitive inhibitors of both MAO-A and MAO-B and were highly selective toward MAO-A. TBO was the most potent inhibitor, followed by TN, BCB, MB, and TB. The dyes studied increased rat pineal N-Acetylserotonin (NAS) and melatonin content, in accordance with our previous observations of the stimulating effect of selective inhibition of MAO-A on pineal melatonin biosynthesis. The redox dyes exerted antidepressant-like activity in frogs; that is, they suppressed the righting reflex in melatonin-primed frogs. This study's results indicate that selective inhibition of MAO-A might mediate the clinical antidepressant effect of MB through NAS stimulation and melatonin biosynthesis.
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effect of luzindole and other melatonin receptor antagonists on iron and lipopolysaccharide induced lipid peroxidation in vitro
2007Co-Authors: Pura J Requintina, Gregory F OxenkrugAbstract:Melatonin and its precursor, N-Acetylserotonin (NAS), have been shown in in vivo and in vitro studies to inhibit iron- and lipopolysaccharide (LPS)-induced lipid peroxidation in rats and mice. Using in vitro studies, we examined whether these effects will be affected by the melatonin receptor antagonists luzindole (a competitive MT(1)/MT(2) antagonist), DH 97 (MT(2)), prazosin (MT(3)), and 4-P-PDOT (MT(2)). Lipid peroxidation in the form of malondialdehyde (MDA) was assayed by measuring thiobarbituric acid-reactive substances. The antagonists did not affect the melatonin and NAS effect on iron- and LPS-induced peroxidation. However, luzindole alone, but not the other antagonists, inhibited the iron- and LPS-induced peroxidation in the rat brain and kidney homogenates. At a dose of 50 microM, luzindole reduced iron-induced MDA levels by 80% in the brain and 84% in the kidney, whereas LPS-induced MDA levels were reduced by 85% in both brain and kidney. A dose of 800 microM prevented lipid peroxidation, bringing the MDA levels to values of samples untreated by iron or LPS.
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antioxidant effects of n acetylserotonin
2005Co-Authors: Gregory F OxenkrugAbstract:: This paper will review our recent data relevant to the antioxidant effects of N-Acetylserotonin (NAS), the immediate precursor of melatonin, the pineal gland indole. Mechanisms of the antioxidant effects of NAS might involve interaction with melatonin type 3 receptors and nonreceptor mechanisms such as stimulation of glutathione peroxidase, an antioxidant enzyme; inhibition of lipid peroxidation; suppression of phospholipase A2 activation; attenuation of tumor necrosis factor-α production; prevention of pathological opening of the mitochondrial permeability transition pores; and inhibition of sepiapterin reductase, the key enzyme of biosynthesis of tetrahydrobiopterin, the essential cofactor of nitric oxide synthase. NAS actions on some of these enzymes might be receptor-mediated. Protective effects of NAS against oxidative damage are independent from the effect of melatonin and, depending on the model, are 5 to 20 times stronger than that of melatonin. Antioxidant effect of NAS might underpin its cognition-enhancing, antiaging, antidepressant, antihypertensive, and antitumor effects. NAS and its derivatives might be useful in protection against oxidative stress-related disorders (cell death, mutagenesis, aging) and diseases (sepsis, cancer, postischemic trauma, Alzheimer's disease, parkinsonism).
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immune modulating effects of melatonin n acetylserotonin and n acetyldopamine
2005Co-Authors: Mary C. Perianayagam, Gregory F Oxenkrug, Bertrand L. JaberAbstract:Melatonin and N-Acetylserotonin (NAS) have antioxidant properties. In the present study, we examined whether melatonin, NAS, and N-acetyldopamine (NAD) have a modulatory effect on tumor necrosis factor-alpha (TNF-alpha) synthesis and superoxide production. Differentiated THP-1-derived human monocytes were coincubated with Escherichia coli lipopolysaccharide (LPS) and rising concentrations of melatonin, NAS, or NAD. After 24 h, TNF-alpha was measured in cell supernatants. In addition, the production of superoxide by HL-60-derived human neutrophils upon stimulation with 4-beta-phorbol 12-beta-myristate 13-alpha-acetate (PMA) or N-formyl methionyl-leucyl-phenylalanine (fMLP) and increasing concentrations of melatonin, NAS, or NAD was determined. Incubation of THP-1-derived monocytes with increasing concentrations of melatonin, NAS, or NAD resulted in a marked decrease in LPS-stimulated TNF-alpha production, which was dose-dependent and on the order of 96-98%. Incubation of HL-60-derived neutrophils with increasing concentrations of melatonin, NAS, or NAD resulted in a modest decrease in PMA-stimulated superoxide production, which was dose-dependent. At the 100 microM dose, melatonin, NAS, or NAD resulted in a 14 +/- 4%, 30 +/- 1%, and 29 +/- 1% decrease in PMA-stimulated superoxide production, respectively. Coincubation of HL-60 cells with melatonin, NAS, or NAD also resulted in a modest dose-dependent decrease in fMLP-stimulated superoxide production. At the 100 microM dose, melatonin, NAS, or NAD resulted in a 13 +/- 1%, 14 +/- 1%, and 14 +/- 1% decrease in superoxide production, respectively. Our results indicate that the inhibitory effect of melatonin, NAS, or NAD on LPS-induced TNF-alpha production is robust and dose-dependent. These compounds are equally effective in attenuating the generation of oxidant radicals, although to a lesser degree.
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mitochondria as a target for neurotoxins and neuroprotective agents
2003Co-Authors: S O Bachurin, Gregory F Oxenkrug, E Shevtsova, E G Kireeva, Sergey O SablinAbstract:A BSTRACT : Mitochondrial permeability transition pores represent a multiprotein complex that includes components of both inner and outer membrane. The pores regulate transport of ions and peptides in and out of mitochondria, and their regulation is associated with a general mechanism for maintaining Ca 2+ homeostasis in the cell and apoptosis. Various pathologic factors may induce a pathologic activation of the permeability transition and an irreversible opening of mitochondria pores. This event is a major step in the development of neurotoxicity and neurodegeneration. This paper explores the effect of MPP + and � -amyloid fragment 25‐35, neurotoxins that are known to generate Parkinson’s-like syndrome and Alzheimer’s disease, on the regulation of the mitochondrial pores. Both neurotoxins induce opening of mitochondrial pores, which is prevented by cyclosporin A, a specific inhibitor of the permeability transition. The effect of MPP + and � -amyloid may be also prevented by an endogenous precursor of melatonin, N -acetylserotonin, by an anti-Alzheimer’s medication tacrine, and by dimebon, which is in development as an agent for the therapy of Alzheimer’s disease and other types of dementia. The paper illustrates that the effect on mitochondrial pores is an important aspect of the mechanism of neurotoxicity. Substances that may prevent opening of mitochondrial pores induced by neurotoxins may preserve the mitochondrial function and, thus, may have potential as neuroprotective agents. K EYWORDS : mitochondria; permeability transition pores; N -acetylserotonin; tacrine; dimebon; neurodegeneration; apoptosis
Elvira Lopeztamames - One of the best experts on this subject based on the ideXlab platform.
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ultrahigh performance liquid chromatography uhplc tandem mass spectrometry ms ms quantification of nine target indoles in sparkling wines
2016Co-Authors: Rebeca Tudela, Susana Buxaderas, M Castellari, Montserrat Riuaumatell, Albert Ribasagusti, Elvira LopeztamamesAbstract:An ultrahigh-performance liquid chromatography (UHPLC)–tandem mass spectrometry (MS/MS) method was developed for the simultaneous determination of nine target indoles in sparkling wines. The proposed method requires minimal sample pretreatment, and its performance parameters (accuracy, repeatability, LOD, and matrix effect) indicate that it is suitable for routine analysis. Four indoles were found at detectable levels in commercial Cava samples: 5-methoxytryptophol (5MTL), tryptophan (TRP), tryptophan ethyl ester (TEE), and N-Acetylserotonin (NSER). Two of them, NSER and 5MTL, are reported here for the first time in sparkling wines, with values of 0.3–2 and 0.29–29.2 μg/L, respectively. In the same samples, the contents of melatonin (MEL), serotonin (SER), 5-hydroxytryptophan (5-OHTRP), 5-hydroxyindole-3-acetic acid (5OHIA), and 5-methoxy-3-indoleacetic acid (5MIA) were all below the corresponding limits of detection.
Shiu Fun Pang - One of the best experts on this subject based on the ideXlab platform.
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binding characteristics and regional distribution of 125i iodomelatonin binding sites in the brain of the human fetus
1991Co-Authors: He Yuan, Shiu Fun PangAbstract:The binding and pharmacological characteristics of [125I]iodomelatonin binding sites in human fetal brain membrane preparations were determined. Membrane preparations of the whole brain revealed a equilibrium binding constant (Kd) of 17.5 pmol/l with a total number of binding sites (Bmax) at 0.8 fmol/mg protein. Among the various brain regions studied, [125I]iodomelatonin binding was highest in the hypothalamus, and lowest in the mid-brain, pons-medulla, and cerebral cortex. The Kd of the hypothalamus was calculated to be 26.1 pmol/l and the Bmax 5.4 fmol/mg protein. Only 6-chloromelatonin, melatonin and N-Acetylserotonin had significant inhibition in the binding. Our results suggest that melatonin receptors are present in the human brain and that melatonin may exert a central action.
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retinal 125i iodomelatonin binding sites in the tree shrew tupaiidae
1991Co-Authors: He Yuan, Shiu Fun PangAbstract:Abstract The characteristics of melatonin-binding sites labelled by [125I]iodomelatonin in membrane preparations from the tree shrew retina were determined. Specific binding of [125I]iodomelatonin to the membrane preparations of tree shrew retina was rapid, stable, saturable, and reversible. Among the indoles tested only 6-chloromelatonin, melatonin and N-Acetylserotonin had significant affinities to the [125I]iodomelatonin binding site. Scatchard analysis of the membrane preparations revealed a dissociation constant (Kd) of 51.0 ± 16 pM and total number of binding sites (Bmax) of 1.97 ± 0.6 fmol/mg protein.
Rebeca Tudela - One of the best experts on this subject based on the ideXlab platform.
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ultrahigh performance liquid chromatography uhplc tandem mass spectrometry ms ms quantification of nine target indoles in sparkling wines
2016Co-Authors: Rebeca Tudela, Susana Buxaderas, M Castellari, Montserrat Riuaumatell, Albert Ribasagusti, Elvira LopeztamamesAbstract:An ultrahigh-performance liquid chromatography (UHPLC)–tandem mass spectrometry (MS/MS) method was developed for the simultaneous determination of nine target indoles in sparkling wines. The proposed method requires minimal sample pretreatment, and its performance parameters (accuracy, repeatability, LOD, and matrix effect) indicate that it is suitable for routine analysis. Four indoles were found at detectable levels in commercial Cava samples: 5-methoxytryptophol (5MTL), tryptophan (TRP), tryptophan ethyl ester (TEE), and N-Acetylserotonin (NSER). Two of them, NSER and 5MTL, are reported here for the first time in sparkling wines, with values of 0.3–2 and 0.29–29.2 μg/L, respectively. In the same samples, the contents of melatonin (MEL), serotonin (SER), 5-hydroxytryptophan (5-OHTRP), 5-hydroxyindole-3-acetic acid (5OHIA), and 5-methoxy-3-indoleacetic acid (5MIA) were all below the corresponding limits of detection.
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Ultrahigh-Performance Liquid Chromatography (UHPLC)–Tandem Mass Spectrometry (MS/MS) Quantification of Nine Target Indoles in Sparkling Wines
2016Co-Authors: Rebeca Tudela, Susana Buxaderas, M Castellari, Albert Ribas-agustí, Montserrat Riu-aumatell, Elvira López-tamamesAbstract:An ultrahigh-performance liquid chromatography (UHPLC)–tandem mass spectrometry (MS/MS) method was developed for the simultaneous determination of nine target indoles in sparkling wines. The proposed method requires minimal sample pretreatment, and its performance parameters (accuracy, repeatability, LOD, and matrix effect) indicate that it is suitable for routine analysis. Four indoles were found at detectable levels in commercial Cava samples: 5-methoxytryptophol (5MTL), tryptophan (TRP), tryptophan ethyl ester (TEE), and N-Acetylserotonin (NSER). Two of them, NSER and 5MTL, are reported here for the first time in sparkling wines, with values of 0.3–2 and 0.29–29.2 μg/L, respectively. In the same samples, the contents of melatonin (MEL), serotonin (SER), 5-hydroxytryptophan (5-OHTRP), 5-hydroxyindole-3-acetic acid (5OHIA), and 5-methoxy-3-indoleacetic acid (5MIA) were all below the corresponding limits of detection
