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Pesquisa : D08.811.913.050.134.127 [Categoria DeCS]
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[PMID]:28466676
[Au] Autor:Backlund PS; Urbanski HF; Doll MA; Hein DW; Bozinoski M; Mason CE; Coon SL; Klein DC
[Ad] Endereço:Biomedical Mass Spectrometry Facility, Intramural Research Program.
[Ti] Título:Daily Rhythm in Plasma N-acetyltryptamine.
[So] Source:J Biol Rhythms;32(3):195-211, 2017 Jun.
[Is] ISSN:1552-4531
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Normal physiology undergoes 24-h changes in function that include daily rhythms in circulating hormones, most notably melatonin and cortical steroids. This study focused on N-acetyltryptamine, a little-studied melatonin receptor mixed agonist-antagonist and the likely evolutionary precursor of melatonin. The central issue addressed was whether N-acetyltryptamine is physiologically present in the circulation. N-acetyltryptamine was detected by LC-MS/MS in daytime plasma of 3 different mammals in subnanomolar levels (mean ± SEM: rat, 0.29 ± 0.05 nM, n = 5; rhesus macaque, 0.54 ± 0.24 nM, n = 4; human, 0.03 ± 0.01 nM, n = 32). Analysis of 24-h blood collections from rhesus macaques revealed a nocturnal increase in plasma N-acetyltryptamine (p < 0.001), which varied from 2- to 15-fold over daytime levels among the 4 animals studied. Related RNA sequencing studies indicated that the transcript encoding the tryptamine acetylating enzyme arylalkylamine N-acetyltransferase (AANAT) is expressed at similar levels in the rhesus pineal gland and retina, thereby indicating that either tissue could contribute to circulating N-acetyltryptamine. The evidence that N-acetyltryptamine is a physiological component of mammalian blood and exhibits a daily rhythm, together with known effects as a melatonin receptor mixed agonist-antagonist, shifts the status of N-acetyltryptamine from pharmacological tool to candidate for a physiological role. This provides a new opportunity to extend our understanding of 24-h biology.
[Mh] Termos MeSH primário: Ritmo Circadiano
Fotoperíodo
Triptaminas/sangue
[Mh] Termos MeSH secundário: Animais
Arilalquilamina N-Acetiltransferase/genética
Perfilação da Expressão Gênica
Seres Humanos
Macaca mulatta
Masculino
Melatonina/metabolismo
Glândula Pineal/enzimologia
Ratos
Retina/enzimologia
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Tryptamines); 1016-47-3 (N-acetyltryptamine); EC 2.3.1.87 (Arylalkylamine N-Acetyltransferase); JL5DK93RCL (Melatonin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1177/0748730417700458


  2 / 290 MEDLINE  
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[PMID]:28699174
[Au] Autor:Gu F; Zhang H; Hyland PL; Berndt S; Gapstur SM; Wheeler W; Ellipse Consortium T; Amos CI; Bezieau S; Bickeböller H; Brenner H; Brennan P; Chang-Claude J; Conti DV; Doherty JA; Gruber SB; Harrison TA; Hayes RB; Hoffmeister M; Houlston RS; Hung RJ; Jenkins MA; Kraft P; Lawrenson K; McKay J; Markt S; Mucci L; Phelan CM; Qu C; Risch A; Rossing MA; Wichmann HE; Shi J; Schernhammer E; Yu K; Landi MT; Caporaso NE
[Ad] Endereço:Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
[Ti] Título:Inherited variation in circadian rhythm genes and risks of prostate cancer and three other cancer sites in combined cancer consortia.
[So] Source:Int J Cancer;141(9):1794-1802, 2017 Nov 01.
[Is] ISSN:1097-0215
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Circadian disruption has been linked to carcinogenesis in animal models, but the evidence in humans is inconclusive. Genetic variation in circadian rhythm genes provides a tool to investigate such associations. We examined associations of genetic variation in nine core circadian rhythm genes and six melatonin pathway genes with risk of colorectal, lung, ovarian and prostate cancers using data from the Genetic Associations and Mechanisms in Oncology (GAME-ON) network. The major results for prostate cancer were replicated in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial, and for colorectal cancer in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). The total number of cancer cases and controls was 15,838/18,159 for colorectal, 14,818/14,227 for prostate, 12,537/17,285 for lung and 4,369/9,123 for ovary. For each cancer site, we conducted gene-based and pathway-based analyses by applying the summary-based Adaptive Rank Truncated Product method (sARTP) on the summary association statistics for each SNP within the candidate gene regions. Aggregate genetic variation in circadian rhythm and melatonin pathways were significantly associated with the risk of prostate cancer in data combining GAME-ON and PLCO, after Bonferroni correction (p < 0.00625). The two most significant genes were NPAS2 (p = 0.0062) and AANAT (p = 0.00078); the latter being significant after Bonferroni correction. For colorectal cancer, we observed a suggestive association with the circadian rhythm pathway in GAME-ON (p = 0.021); this association was not confirmed in GECCO (p = 0.76) or the combined data (p = 0.17). No significant association was observed for ovarian and lung cancer. These findings support a potential role for circadian rhythm and melatonin pathways in prostate carcinogenesis. Further functional studies are needed to better understand the underlying biologic mechanisms.
[Mh] Termos MeSH primário: Arilalquilamina N-Acetiltransferase/genética
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética
Ritmo Circadiano/genética
Neoplasias Colorretais/genética
Proteínas do Tecido Nervoso/genética
Neoplasias da Próstata/genética
[Mh] Termos MeSH secundário: Carcinogênese/genética
Neoplasias Colorretais/patologia
Feminino
Estudos de Associação Genética
Predisposição Genética para Doença
Seres Humanos
Neoplasias Pulmonares/genética
Neoplasias Pulmonares/patologia
Masculino
Neoplasias Ovarianas/genética
Neoplasias Ovarianas/patologia
Polimorfismo de Nucleotídeo Único
Neoplasias da Próstata/patologia
Transdução de Sinais/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Basic Helix-Loop-Helix Transcription Factors); 0 (NPAS2 protein, human); 0 (Nerve Tissue Proteins); EC 2.3.1.87 (AANAT protein, human); EC 2.3.1.87 (Arylalkylamine N-Acetyltransferase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170713
[St] Status:MEDLINE
[do] DOI:10.1002/ijc.30883


  3 / 290 MEDLINE  
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[PMID]:28675567
[Au] Autor:Rohde K; Bering T; Furukawa T; Rath MF
[Ad] Endereço:Department of Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
[Ti] Título:A modulatory role of the Rax homeobox gene in mature pineal gland function: Investigating the photoneuroendocrine circadian system of a Rax conditional knockout mouse.
[So] Source:J Neurochem;143(1):100-111, 2017 Oct.
[Is] ISSN:1471-4159
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The retinal and anterior neural fold homeobox gene (Rax) controls development of the eye and the forebrain. Postnatal expression of Rax in the brain is restricted to the pineal gland, a forebrain structure devoted to melatonin synthesis. The role of Rax in pineal function is unknown. In order to investigate the role of Rax in pineal function while circumventing forebrain abnormalities of the global Rax knockout, we generated an eye and pineal-specific Rax conditional knockout mouse. Deletion of Rax in the pineal gland did not affect morphology of the gland, suggesting that Rax is not essential for pineal gland development. In contrast, deletion of Rax in the eye generated an anophthalmic phenotype. In addition to the loss of central visual pathways, the suprachiasmatic nucleus of the hypothalamus housing the circadian clock was absent, indicating that the retinohypothalamic tract is required for the nucleus to develop. Telemetric analyses confirmed the lack of a functional circadian clock. Arylalkylamine N-acetyltransferase (Aanat) transcripts, encoding the melatonin rhythm-generating enzyme, were undetectable in the pineal gland of the Rax conditional knockout under normal conditions, whereas the paired box 6 homeobox gene, known to regulate pineal development, was up-regulated. By injecting isoproterenol, which mimics a nocturnal situation in the pineal gland, we were able to induce pineal expression of Aanat in the Rax conditional knockout mouse, but Aanat transcript levels were significantly lower than those of Rax-proficient mice. Our data suggest that Rax controls pineal gene expression and via Aanat may modulate melatonin synthesis.
[Mh] Termos MeSH primário: Ritmo Circadiano/fisiologia
Proteínas do Olho/fisiologia
Genes Homeobox/fisiologia
Proteínas de Homeodomínio/fisiologia
Glândula Pineal/metabolismo
Núcleo Supraquiasmático/metabolismo
Fatores de Transcrição/fisiologia
Vias Visuais/metabolismo
[Mh] Termos MeSH secundário: Animais
Arilalquilamina N-Acetiltransferase/biossíntese
Arilalquilamina N-Acetiltransferase/genética
Proteínas do Olho/genética
Feminino
Perfilação da Expressão Gênica/métodos
Proteínas de Homeodomínio/genética
Masculino
Camundongos
Camundongos da Linhagem 129
Camundongos Knockout
Células Neuroendócrinas/metabolismo
Retina/metabolismo
Fatores de Transcrição/deficiência
Fatores de Transcrição/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Eye Proteins); 0 (Homeodomain Proteins); 0 (Rax protein, mouse); 0 (Transcription Factors); EC 2.3.1.87 (AANAT protein, human); EC 2.3.1.87 (Arylalkylamine N-Acetyltransferase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170705
[St] Status:MEDLINE
[do] DOI:10.1111/jnc.14120


  4 / 290 MEDLINE  
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[PMID]:28655604
[Au] Autor:Alkozi HA; Perez de Lara MJ; Pintor J
[Ad] Endereço:Department of Biochemistry and Molecular Biology IV, Faculty of Optics and Optometry, Universidad Complutense de Madrid, Madrid, Spain.
[Ti] Título:Melatonin synthesis in the human ciliary body triggered by TRPV4 activation: Involvement of AANAT phosphorylation.
[So] Source:Exp Eye Res;162:1-8, 2017 Sep.
[Is] ISSN:1096-0007
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Melatonin is a substance synthesized in the pineal gland as well as in other organs. This substance is involved in many ocular functions, giving its synthesis in numerous eye structures. Melatonin is synthesized from serotonin through two enzymes, the first limiting step into the synthesis of melatonin being aralkylamine N-acetyltransferase (AANAT). In this current study, AANAT phosphorylation after the activation of TRPV4 was studied using human non-pigmented epithelial ciliary body cells. Firstly, it was necessary to determine the adequate time and dose of the TRPV4 agonist GSK1016790A to reach the maximal phosphorylation of AANAT. An increase of 72% was observed after 5 min incubation with 10 nM GSK (**p < 0.05, n = 6) with a concomitant rise in N-acetyl serotonin and melatonin synthesis. The involvement of a TRPV4 channel in melatonin synthesis was verified by antagonist and siRNA studies as a previous step to studying intracellular signalling. Studies performed on the second messengers involved in GSK induced AANAT phosphorylation were carried out by inhibiting several pathways. In conclusion, the activation of calmodulin and calmodulin-dependent protein kinase II was confirmed, as shown by the cascade seen in AANAT phosphorylation (***p < 0.001, n = 4). This mechanism was also established by measuring N-acetyl serotonin and melatonin levels. In conclusion, the activation of a TRPV4 present in human ciliary body epithelial cells produced an increase in AANAT phosphorylation and a further melatonin increase by a mechanism in which Ca-calmodulin and the calmodulin-dependent protein kinase II are involved.
[Mh] Termos MeSH primário: Arilalquilamina N-Acetiltransferase/metabolismo
Corpo Ciliar/metabolismo
Células Epiteliais/metabolismo
Melatonina/biossíntese
Canais de Cátion TRPV/metabolismo
[Mh] Termos MeSH secundário: Western Blotting
Linhagem Celular
Cromatografia Líquida de Alta Pressão
Corpo Ciliar/citologia
Células Epiteliais/citologia
Seres Humanos
Fosforilação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (TRPV Cation Channels); 0 (TRPV4 protein, human); EC 2.3.1.87 (AANAT protein, human); EC 2.3.1.87 (Arylalkylamine N-Acetyltransferase); JL5DK93RCL (Melatonin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170901
[Lr] Data última revisão:
170901
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170629
[St] Status:MEDLINE


  5 / 290 MEDLINE  
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[PMID]:28577421
[Au] Autor:Singh KM; Saha S; Gupta BBP
[Ad] Endereço:Environmental Endocrinology Laboratory, Department of Zoology, North-Eastern Hill University, Shillong 793022, India.
[Ti] Título:Season-dependent effects of photoperiod and temperature on circadian rhythm of arylalkylamine N-acetyltransferase2 gene expression in pineal organ of an air-breathing catfish, Clarias gariepinus.
[So] Source:J Photochem Photobiol B;173:140-149, 2017 Aug.
[Is] ISSN:1873-2682
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Arylalkylamine N-acetyltransferase (AANAT) activity, aanat gene expression and melatonin production have been reported to exhibit prominent circadian rhythm in the pineal organ of most species of fish. Three types of aanat genes are expressed in fish, but the fish pineal organ predominantly expresses aanat2 gene. Increase and decrease in daylength is invariably associated with increase and decrease in temperature, respectively. But so far no attempt has been made to delineate the role of photoperiod and temperature in regulation of the circadian rhythm of aanat2 gene expression in the pineal organ of any fish with special reference to seasons. Therefore, we studied effects of various lighting regimes (12L-12D, 16L-8D, 8L-16D, LL and DD) at a constant temperature (25°C) and effects of different temperatures (15°, 25° and 35°C) under a common photoperiod 12L-12D on circadian rhythm of aanat2 gene expression in the pineal organ of Clarias gariepinus during summer and winter seasons. Aanat2 gene expression in fish pineal organ was studied by measuring aanat2 mRNA levels using Real-Time PCR. Our findings indicate that the pineal organ of C. gariepinus exhibits a prominent circadian rhythm of aanat2 gene expression irrespective of photoperiods, temperatures and seasons, and the circadian rhythm of aanat2 gene expression responds differently to different photoperiods and temperatures in a season-dependent manner. Existence of circadian rhythm of aanat2 gene expression in pineal organs maintained in vitro under 12L-12D and DD conditions as well as a free running rhythm of the gene expression in pineal organ of the fish maintained under LL and DD conditions suggest that the fish pineal organ possesses an endogenous circadian oscillator, which is entrained by light-dark cycle.
[Mh] Termos MeSH primário: Arilalquilamina N-Acetiltransferase/genética
Peixes-Gato
Ritmo Circadiano/fisiologia
Fotoperíodo
Glândula Pineal/enzimologia
Estações do Ano
Temperatura Ambiente
[Mh] Termos MeSH secundário: Animais
Arilalquilamina N-Acetiltransferase/classificação
Arilalquilamina N-Acetiltransferase/metabolismo
Peixes-Gato/genética
Peixes-Gato/metabolismo
Expressão Gênica/efeitos da radiação
Luz
Masculino
Melatonina/metabolismo
Filogenia
RNA Mensageiro/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Messenger); EC 2.3.1.87 (Arylalkylamine N-Acetyltransferase); JL5DK93RCL (Melatonin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170604
[St] Status:MEDLINE


  6 / 290 MEDLINE  
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[PMID]:28486510
[Au] Autor:Aboalroub AA; Bachman AB; Zhang Z; Keramisanou D; Merkler DJ; Gelis I
[Ad] Endereço:Department of Chemistry, University of South Florida, Tampa, Florida, United States of America.
[Ti] Título:Acetyl group coordinated progression through the catalytic cycle of an arylalkylamine N-acetyltransferase.
[So] Source:PLoS One;12(5):e0177270, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The transfer of an acetyl group from acetyl-CoA to an acceptor amine is a ubiquitous biochemical transformation catalyzed by Gcn5-related N-acetyltransferases (GNATs). Although it is established that the reaction proceeds through a sequential ordered mechanism, the role of the acetyl group in driving the ordered formation of binary and ternary complexes remains elusive. Herein, we show that CoA and acetyl-CoA alter the conformation of the substrate binding site of an arylalkylamine N-acetyltransferase (AANAT) to facilitate interaction with acceptor substrates. However, it is the presence of the acetyl group within the catalytic funnel that triggers high affinity binding. Acetyl group occupancy is relayed through a conserved salt bridge between the P-loop and the acceptor binding site, and is manifested as differential dynamics in the CoA and acetyl-CoA-bound states. The capacity of the acetyl group carried by an acceptor to promote its tight binding even in the absence of CoA, but also its mutually exclusive position to the acetyl group of acetyl-CoA underscore its importance in coordinating the progression of the catalytic cycle.
[Mh] Termos MeSH primário: Arilalquilamina N-Acetiltransferase/metabolismo
[Mh] Termos MeSH secundário: Catálise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.3.1.87 (Arylalkylamine N-Acetyltransferase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170510
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0177270


  7 / 290 MEDLINE  
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[PMID]:28368307
[Au] Autor:Alkozi HA; Perez de Lara MJ; Sánchez-Naves J; Pintor J
[Ad] Endereço:Department of Biochemistry and Molecular Biology IV, Faculty of Optics and Optometry, University Complutense of Madrid, 28040 Madrid, Spain. Hanan-q1@live.com.
[Ti] Título:TRPV4 Stimulation Induced Melatonin Secretion by Increasing Arylalkymine N-acetyltransferase (AANAT) Protein Level.
[So] Source:Int J Mol Sci;18(4), 2017 Apr 01.
[Is] ISSN:1422-0067
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Melatonin is a molecule which has gained a great deal of interest in many areas of science; its synthesis was classically known to be in the pineal gland. However, many organs synthesize melatonin, such as several ocular structures. Melatonin is known to participate in many functions apart from its main action regulating the circadian rhythm. It is synthesized from serotonin in two steps, with a rate-limiting step carried out by arylalkymine -acetyltransferase (AANAT). In this report, the role of TRPV4 channel present in human ciliary body epithelial cells in AANAT production was studied. Several experiments were undertaken to verify the adequate time to reach the maximal effect by using the TRPV4 agonist GSK1016790A, together with a dose-response study. An increase of 2.4 folds in AANAT was seen after 18 h of incubation with 10 nM of GSK1016790A ( < 0.001, = 6). This increment was verified by antagonist assays. In summary, AANAT levels and therefore melatonin synthesis change after TRPV4 channel stimulation. Using this cell model together with human ciliary body tissue it is possible to suggest that AANAT plays an important role in pathologies related to intraocular pressure.
[Mh] Termos MeSH primário: Arilalquilamina N-Acetiltransferase/metabolismo
Células Epiteliais/metabolismo
Melatonina/secreção
Canais de Cátion TRPV/metabolismo
[Mh] Termos MeSH secundário: Western Blotting
Linhagem Celular
Corpo Ciliar/citologia
Relação Dose-Resposta a Droga
Células Epiteliais/efeitos dos fármacos
Seres Humanos
Leucina/análogos & derivados
Leucina/farmacologia
Microscopia Confocal
Modelos Biológicos
Fosforilação/efeitos dos fármacos
Serotonina/análogos & derivados
Serotonina/metabolismo
Sulfonamidas/farmacologia
Canais de Cátion TRPV/agonistas
Canais de Cátion TRPV/antagonistas & inibidores
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (N-(1-((4-(2-(((2,4-dichlorophenyl)sulfonyl)amino)-3-hydroxypropanoyl)-1-piperazinyl)carbonyl)-3-methylbutyl)-1-benzothiophene-2-carboxamide); 0 (RN 1734); 0 (Sulfonamides); 0 (TRPV Cation Channels); 0 (TRPV4 protein, human); 333DO1RDJY (Serotonin); EC 2.3.1.87 (AANAT protein, human); EC 2.3.1.87 (Arylalkylamine N-Acetyltransferase); GMW67QNF9C (Leucine); JL5DK93RCL (Melatonin); P4TO3C82WV (N-acetylserotonin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170613
[Lr] Data última revisão:
170613
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170404
[St] Status:MEDLINE


  8 / 290 MEDLINE  
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[PMID]:28315773
[Au] Autor:Kulczykowska E; Kleszczynska A; Gozdowska M; Sokolowska E
[Ad] Endereço:Department of Genetics and Marine Biotechnology, Institute of Oceanology, Polish Academy of Sciences, Powstanców Warszawy 55 Str., 81-712 Sopot, Poland. Electronic address: ekulczykowska@iopan.gda.pl.
[Ti] Título:The time enzyme in melatonin biosynthesis in fish: Day/night expressions of three aralkylamine N-acetyltransferase genes in three-spined stickleback.
[So] Source:Comp Biochem Physiol A Mol Integr Physiol;208:46-53, 2017 Jun.
[Is] ISSN:1531-4332
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In vertebrates, aralkylamine N-acetyltransferase (AANAT; EC 2.3.1.87) is a time-keeping enzyme in melatonin (Mel) biosynthesis. Uniquely in fish, there are several AANAT isozymes belonging to two AANAT subfamilies, AANAT1 and AANAT2, which are encoded by distinct genes. The different substrate preferences, kinetics and spatial expression patterns of isozymes indicate that they may have different functions. In the three-spined stickleback (Gasterosteus aculeatus), there are three genes encoding three AANAT isozymes. In this study, for the first time, the levels of aanat1a, aanat1b and aanat2 mRNAs are measured by absolute RT-qPCR in the brain, eye, skin, stomach, gut, heart and kidney collected at noon and midnight. Melatonin levels are analysed by HPLC with fluorescence detection in homogenates of the brain, eye, skin and kidney. The levels of aanats mRNAs differ significantly within and among organs. In the brain, eye, stomach and gut, there are day/night variations in aanats mRNAs levels. The highest levels of aanat1a and aanat1b mRNAs are in the eye. The extremely high expressions of these genes which are reflected in the highest Mel concentrations at this site at noon and midnight strongly suggest that the eye is an important source of the hormone in the three-spined sticklebacks. A very low level of aanat2 mRNA in all organs may suggest that AANAT1a and/or AANAT1b are principal isozymes in the three-spine sticklebacks. A presence of the isozymes of defined substrate preferences provides opportunity for control of acetylation of amines by modulation of individual aanat expression and permits the fine-tuning of indolethylamines and phenylethylamines metabolism to meet the particular needs of a given organ.
[Mh] Termos MeSH primário: Arilalquilamina N-Acetiltransferase/genética
Ritmo Circadiano/genética
Melatonina/genética
Smegmamorpha/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos/genética
Animais
Arilalquilamina N-Acetiltransferase/biossíntese
Clonagem Molecular
Regulação Enzimológica da Expressão Gênica
Melatonina/biossíntese
Smegmamorpha/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
EC 2.3.1.87 (Arylalkylamine N-Acetyltransferase); JL5DK93RCL (Melatonin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170807
[Lr] Data última revisão:
170807
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170320
[St] Status:MEDLINE


  9 / 290 MEDLINE  
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[PMID]:28236225
[Au] Autor:Aboalroub AA; Zhang Z; Keramisanou D; Gelis I
[Ad] Endereço:Chemistry Department, University of South Florida, Tampa, FL, 33620, USA.
[Ti] Título:Backbone resonance assignment of an insect arylalkylamine N-acetyltransferase from Bombyx mori reveals conformational heterogeneity.
[So] Source:Biomol NMR Assign;11(1):105-109, 2017 Apr.
[Is] ISSN:1874-270X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Arylalkylamine N-acetyltransferases (AANATs) catalyze the transfer of an acetyl group from the acetyl-group donor, acetyl-CoA, to an arylalkylamine acceptor. Although a single AANAT has been identified in mammals, insects utilize multiple AANATs in a diverse array of biological processes. AANATs belong to the GCN5-related acetyltransferase (GNAT) superfamily of enzymes, which despite their overall very low sequence homology, are characterized by a well conserved catalytic core domain. The structural properties of many GNATs have been extensively studied by X-ray crystallography that revealed common features during the catalytic cycle. Here we report the H, C and N backbone NMR resonance assignment of the 24 kDa AANAT3 from Bombyx mori (bmAANAT3) as a first step towards understanding the role of protein dynamics in the catalytic properties of AANATs. Our preliminary solution NMR studies reveal that bmAANAT3 is well-folded in solution. The P-loop, which is responsible for cofactor binding, is flexible in the free-state, while a large region of the enzyme interconverts between two distinct conformations in the slow exchange regime.
[Mh] Termos MeSH primário: Arilalquilamina N-Acetiltransferase/química
Arilalquilamina N-Acetiltransferase/metabolismo
Bombyx/enzimologia
Ressonância Magnética Nuclear Biomolecular
[Mh] Termos MeSH secundário: Animais
Biocatálise
Modelos Moleculares
Conformação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.3.1.87 (Arylalkylamine N-Acetyltransferase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170226
[St] Status:MEDLINE
[do] DOI:10.1007/s12104-017-9729-8


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[PMID]:28118532
[Au] Autor:Li Y; Hu N; Yang D; Oxenkrug G; Yang Q
[Ad] Endereço:State Key Laboratory of Genetic Engineering, Department of Biochemistry, School of Life Sciences, Fudan University, Shanghai, China.
[Ti] Título:Regulating the balance between the kynurenine and serotonin pathways of tryptophan metabolism.
[So] Source:FEBS J;284(6):948-966, 2017 Mar.
[Is] ISSN:1742-4658
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Tryptophan is metabolized along the kynurenine and serotonin pathways, resulting in formation of kynurenine metabolites, neuroactive serotonin and melatonin. Each pathway is critical for maintaining healthy homeostasis. However, the two pathways are extremely unequal in their ability to degrade tryptophan, and little is known about the mechanisms maintaining the balance between them. Here, we demonstrated that in PC12 cells, a change of expression of key genes of one pathway resulted in a change of expression of key genes of the other. Melatonin, the end product of the serotonin pathway, played an important role in tryptophan metabolism by affecting both key enzymes of the two pathways. Melatonin treatment induced the expression of indole-2,3-dioxygenase 1 (IDO1) and enhanced the activity of the IDO1 promoter while decreasing the expression of arylalkylamine N-acetyl transferase. Melatonin treatment up-regulated the expression of forkhead box protein O1 (FoxO1) and enhanced the binding of FoxO1 to the IDO1 promoter. FoxO1 was shown to be a new regulator for IDO1 expression. Melatonin treatment decreased the phosphorylation of FoxO1 by extracellular signal-regulated kinases 1 and 2 and protein kinase B (Akt) and increased the phosphorylation of binding protein 14-3-3 by c-Jun N-terminal kinase (JNK), and thus the complex of FoxO1-14-3-3 in the cytoplasm was disassembled and FoxO1 was relocated to the nucleus to induce IDO1 expression. The JNK signaling pathway played an important role in melatonin-induced IDO1 up-regulation. In conclusion, this study suggests a link between melatonin, JNK, FoxO1 and IDO1 that acts as a potential balance regulator of tryptophan metabolism, and offers a new approach to treat diseases related to dysregulation of tryptophan metabolism.
[Mh] Termos MeSH primário: Indolamina-Pirrol 2,3,-Dioxigenase/genética
MAP Quinase Quinase 4/genética
Proteínas do Tecido Nervoso/genética
Triptofano/metabolismo
[Mh] Termos MeSH secundário: Animais
Arilalquilamina N-Acetiltransferase/genética
Arilalquilamina N-Acetiltransferase/metabolismo
Regulação da Expressão Gênica
Seres Humanos
Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo
Cinurenina/metabolismo
MAP Quinase Quinase 4/metabolismo
Melatonina/administração & dosagem
Melatonina/metabolismo
Redes e Vias Metabólicas/genética
Proteínas do Tecido Nervoso/metabolismo
Proteína Oncogênica v-akt/genética
Proteína Oncogênica v-akt/metabolismo
Células PC12
Regiões Promotoras Genéticas
Ratos
Serotonina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Indoleamine-Pyrrole 2,3,-Dioxygenase); 0 (Nerve Tissue Proteins); 147604-79-3 (Foxo1 protein, rat); 333DO1RDJY (Serotonin); 343-65-7 (Kynurenine); 8DUH1N11BX (Tryptophan); EC 2.3.1.87 (Arylalkylamine N-Acetyltransferase); EC 2.7.11.1 (Oncogene Protein v-akt); EC 2.7.12.2 (MAP Kinase Kinase 4); JL5DK93RCL (Melatonin)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170704
[Lr] Data última revisão:
170704
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170125
[St] Status:MEDLINE
[do] DOI:10.1111/febs.14026



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