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tryptophan hydroxylase

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https://www.readbyqxmd.com/read/28534121/organic-anion-transporters-oat1-and-oat3-are-crucial-biopterin-transporters-involved-in-bodily-distribution-of-tetrahydrobiopterin-and-exclusion-of-its-excess
#1
Akiko Ohashi, Kaori Mamada, Tomonori Harada, Masako Naito, Tomihisa Takahashi, Shin Aizawa, Hiroyuki Hasegawa
Tetrahydrobiopterin (BH4) is a common coenzyme of phenylalanine-, tyrosine-, and tryptophan hydroxylases, alkylglycerol monooxygenase, and NO synthases (NOS). Synthetic BH4 is used medicinally for BH4-responsive phenylketonuria and inherited BH4 deficiency. BH4 supplementation has also drawn attention as a therapy for various NOS-related cardio-vascular diseases, but its use has met with limited success in decreasing BH2, the oxidized form of BH4. An increase in the BH2/BH4 ratio leads to NOS dysfunction. Previous studies revealed that BH4 supplementation caused a rapid urinary loss of BH4 accompanied by an increase in the blood BH2/BH4 ratio and an involvement of probenecid-sensitive but unknown transporters was strongly suggested in these processes...
May 22, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28529483/identification-of-a-novel-allosteric-inhibitory-site-on-tryptophan-hydroxylase-1-enabling-unprecedented-selectivity-over-all-related-hydroxylases
#2
Mike Petrassi, Rob Barber, Celine Be, Sarah Beach, Brian Cox, Anne-Marie D'Souza, Nick Duggan, Martin Hussey, Roy Fox, Peter Hunt, Gabor Jarai, Takatoshi Kosaka, Paul Oakley, Viral Patel, Neil Press, David Rowlands, Clemens Scheufler, Oliver Schmidt, Honnappa Srinivas, Mary Turner, Rob Turner, John Westwick, Alison Wolfreys, Nuzhat Pathan, Simon Watson, Matthew Thomas
Pulmonary arterial hypertension (PAH) has demonstrated multi-serotonin receptor dependent pathologies, characterized by increased tone (5-HT1B receptor) and complex lesions (SERT, 5-HT1B, 5-HT2B receptors) of the pulmonary vasculature together with right ventricular hypertrophy, ischemia and fibrosis (5-HT2B receptor). Selective inhibitors of individual signaling elements - SERT, 5-HT2A, 5HT2B, and combined 5-HT2A/B receptors, have all been tested clinically and failed. Thus, inhibition of tryptophan hydroxylase 1 (TPH1), the rate limiting step in 5-HT synthesis, has been suggested as a more broad, and thereby more effective, mode of 5-HT inhibition...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28505018/the-variation-of-the-5-hydroxytryptamine-system-between-chronic-unpredictable-mild-stress-rats-and-chronic-fatigue-syndrome-rats-induced-by-forced-treadmill-running
#3
Yin Cao, Qinglin Li
The aim of this study was to observe the variation in the 5-hydroxytryptamine (5-HT) system between a chronic unpredictable mild stress (CUMS) model and a chronic fatigue syndrome (CFS) model. The total distance, the crossing pieces, and rearing times in the open-field test of the CUMS group and the CFS group were all less than those of the control group to different degrees. The concentrations of tryptophan, 5-HT, and 5-HIAA of the CUMS group were obviously lower than those of the control group. In the CFS model, the concentrations of tryptophan, 5-HT, and 5-HIAA were obviously higher than those of the control group...
May 12, 2017: Neuroreport
https://www.readbyqxmd.com/read/28503523/treadmill-exercise-ameliorates-depressive-symptoms-through-increasing-serotonin-expression-in-postpartum-depression-rats
#4
Eun-Sang Ji, Jae-Min Lee, Tae-Woon Kim, You-Mi Kim, Yeon-Soo Kim, Kijeong Kim
Postpartum depression (PPD) is defined as the depressive symptoms that occur from the moment of delivery until 12 months after delivery. PPD symptoms are closely associated with reduced activity of the serotonergic system. Serotonin (5-hydroxytryptamine, 5-HT) plays an important role in the pathogenesis of depression. Tryptophan hydroxylase (TPH) catalyzes the rate-limiting step of 5-HT biosynthesis in the serotonergic neurons. Exercise exerts anti-depressive effect on depression patients as well as on animal models of depression...
April 2017: Journal of Exercise Rehabilitation
https://www.readbyqxmd.com/read/28503522/treadmill-exercise-alleviates-depressive-symptoms-in-rotenone-induced-parkinson-disease-rats
#5
Mal-Soon Shin, Tae-Woon Kim, Jae-Min Lee, Yun-Hee Sung, Baek-Vin Lim
Parkinson disease (PD) is characterized by selective loss of the dopaminergic neurons. The symptoms of depression following PD are closely associated with reduced activity of the serotonergic system in the dorsal raphe. We explored the antidepressive effect of exercise and its possible mechanism using the rotenone-induced PD rats. PD rats were induced by subcutaneously injection with rotenone for 14 days. The rats in the exercise groups were made to run on a treadmill for 30 min once a day during 14 consecutive days...
April 2017: Journal of Exercise Rehabilitation
https://www.readbyqxmd.com/read/28487998/effects-of-dietary-l-tryptophan-supplementation-on-intestinal-response-to-chronic-unpredictable-stress-in-broilers
#6
Yunshuang Yue, Yuming Guo, Ying Yang
Stress has been recognized as a critical risk factor for gastrointestinal diseases in both humans and animals. However, nutritional strategies to attenuate stress-induced intestinal barrier function and underlying mechanisms remain largely unknown. This study tested the hypothesis that L-tryptophan enhanced intestinal barrier function by regulating mucosal serotonin metabolism in chronic unpredictable stress-exposed broilers. One-day-old male broilers (Arbor Acres) were fed a basal diet supplemented with or without L-tryptophan in the absence or presence of chronic unpredictable stress...
May 9, 2017: Amino Acids
https://www.readbyqxmd.com/read/28474748/connexin36-localization-to-pinealocytes-in-the-pineal-gland-of-mouse-and-rat
#7
S G Wang, D D Tsao, K G Vanderpool, T Yasumura, J E Rash, J I Nagy
Several cell types in the pineal gland are known to establish intercellular gap junctions, but the connexin constituents of those junctions have not been fully characterized. Specifically, the expression of connexin36 (Cx36) protein and mRNA has been examined in the pineal, but the identity of cells that produce Cx36 and that form Cx36-containing gap junctions has not been determined. We used immunofluorescence and freeze fracture replica immunogold labelling (FRIL) of Cx36 to investigate the cellular and subcellular localization of Cx36 in the pineal gland of adult mouse and rat...
May 5, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28465562/activation-of-the-ileal-neuroendocrine-tumor-cell-line-p-sts-by-acetylcholine-is-amplified-by-histamine-role-of-h3r-and-h4r
#8
Beatrix Pfanzagl, Diana Mechtcheriakova, Anastasia Meshcheryakova, Stephan W Aberle, Roswitha Pfragner, Erika Jensen-Jarolim
Neuroendocrine tumors may present with pseudoallergic reactions like diarrhea and idiopathic anaphylaxis. Here we present the P-STS human ileal neuroendocrine cell line as a model cell line for these tumors. Neuroendocrine markers and changes in cytoplasmic calcium concentration ([Ca(2+)]i) in response to several possible activators of 5-hydroxytryptamine (5-HT) release were analyzed. P-STS cells still expressed chromogranin A and synaptophysin after 2 years of culture. Tryptophan hydroxylase 1 mRNA and a low amount of 5-HT were also detected...
May 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28464229/functional-characterization-of-the-neuron-restrictive-silencer-element-in-the-human-tryptophan-hydroxylase-2-gene-expression
#9
Yukino Nawa, Hanae Kaneko, Masayuki Oda, Masaaki Tsubonoya, Tomoko Hiroi, Maria Teresa Gentile, Luca Colucci-D'Amato, Ryoya Takahashi, Hiroaki Matsui
Tryptophan hydroxylase 2 (TPH2) is the key enzyme in the synthesis of neuronal serotonin. Although previous studies suggest that TPH2 NRSE (neuron-restrictive silencer element) functions as a negative regulator dependent on NRSF (neuron-restrictive silencer factor) activity, the underlying mechanisms are yet to be fully elucidated. Here, we show a detailed analysis of the NRSE-mediated repression of the human TPH2 (hTPH2) promoter activity in RN46A cells, a cell line derived from rat raphe neurons. Quantitative real-time RT-PCR analysis revealed the expression of serotonergic marker genes (Mash1, Nkx2...
May 2, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28463726/amitraz-changes-ne-da-and-5-ht-biosynthesis-and-metabolism-mediated-by-alterations-in-estradiol-content-in-cns-of-male-rats
#10
Javier Del Pino, Paula Moyano, Matilde Ruiz, María José Anadón, María Jesús Díaz, José Manuel García, Elena Labajo-González, María Teresa Frejo
Amitraz is a formamidine insecticide/acaricide that alters different neurotransmitters levels, among other neurotoxic effects. Oral amitraz exposure (20, 50 and 80 mg/kg bw, 5 days) has been reported to increase serotonin (5-HT), norepinephrine (NE) and dopamine (DA) content and to decrease their metabolites and turnover rates in the male rat brain, particularly in the striatum, prefrontal cortex, and hippocampus. However, the mechanisms by which these alterations are produced are not completely understood...
August 2017: Chemosphere
https://www.readbyqxmd.com/read/28458330/gender-differences-in-serotonin-signaling-in-patients-with-diarrhea-predominant-irritable-bowel-syndrome
#11
Ryo Katsumata, Akiko Shiotani, Takahisa Murao, Manabu Ishii, Minoru Fujita, Hiroshi Matsumoto, Ken Haruma
Objective Gender differences, including differences in the prevalence, subtypes and the effectiveness of treatment, are generally recognized in irritable bowel syndrome (IBS). Although serotonin type 3 receptor (5-HT3R) antagonists appear to be more effective in women with diarrhea predominant IBS (IBS-D) than they are in men, the mechanisms underlying these effects remain unclear. The aim of the present was to investigate the gender differences in 5-HT signaling. Methods The subjects were selected from outpatients with IBS-D and healthy controls...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28443016/genetics-of-aggression-in-alzheimer-s-disease-ad
#12
Walter J Lukiw, Evgeny I Rogaev
Alzheimer's disease (AD) is a terminal, age-related neurological syndrome exhibiting progressive cognitive and memory decline, however AD patients in addition exhibit ancillary neuropsychiatric symptoms (NPSs) and these include aggression. In this communication we provide recent evidence for the mis-regulation of a small family of genes expressed in the human hippocampus that appear to be significantly involved in expression patterns common to both AD and aggression. DNA array- and mRNA transcriptome-based gene expression analysis and candidate gene association and/or genome-wide association studies (CGAS, GWAS) of aggressive attributes in humans have revealed a surprisingly small subset of six brain genes that are also strongly associated with altered gene expression patterns in AD...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28434116/activation-of-the-serotonin-pathway-is-associated-with-poor-outcome-in-copd-exacerbation-results-of-a-long-term-cohort-study
#13
Marc A Meier, Manuel Ottiger, Alaadin Vögeli, Christian Steuer, Luca Bernasconi, Robert Thomann, Mirjam Christ-Crain, Christoph Henzen, Claus Hoess, Werner Zimmerli, Andreas Huber, Beat Mueller, Philipp Schuetz
BACKGROUND/INTRODUCTION: Indoleamine 2,3-dioxygenase (IDO) metabolizes tryptophan to kynurenine. An increase of its activity is associated with severity in patients with pneumonia. In chronic obstructive pulmonary disease (COPD) patients, an elevation of serotonin has been reported. Experimental models showed that cigarette smoke inhibits monoamine oxidase (MAO) leading to higher levels of serotonin. We investigated the prognostic ability of tryptophan, serotonin, kynurenine, IDO, and tryptophan hydroxylase (TPH) to predict short- and long-term outcomes in patients with a COPD exacerbation...
April 22, 2017: Lung
https://www.readbyqxmd.com/read/28404880/serotonergic-system-antagonists-target-breast-tumor-initiating-cells-and-synergize-with-chemotherapy-to-shrink-human-breast-tumor-xenografts
#14
William D Gwynne, Robin M Hallett, Adele Girgis-Gabardo, Bojana Bojovic, Anna Dvorkin-Gheva, Craig Aarts, Kay Dias, Anita Bane, John A Hassell
Breast tumors comprise an infrequent tumor cell population, termed breast tumor initiating cells (BTIC), which sustain tumor growth, seed metastases and resist cytotoxic therapies. Hence therapies are needed to target BTIC to provide more durable breast cancer remissions than are currently achieved. We previously reported that serotonergic system antagonists abrogated the activity of mouse BTIC resident in the mammary tumors of a HER2-overexpressing model of breast cancer. Here we report that antagonists of serotonin (5-hydroxytryptamine; 5-HT) biosynthesis and activity, including US Federal Food and Drug Administration (FDA)-approved antidepressants, targeted BTIC resident in numerous breast tumor cell lines regardless of their clinical or molecular subtype...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28394432/immunofluorescence-reveals-unusual-patterns-of-labelling-for-connexin43-localized-to-calbindin-d28k-positive-interstitial-cells-in-the-pineal-gland
#15
D D Tsao, S G Wang, B D Lynn, J I Nagy
Gap junctions between cells in the pineal gland have been described ultrastructurally, but their connexin constituents have not been fully characterized. We used immunofluorescence in combination with markers of pineal cells to document the cellular localization of connexin43 (Cx43). Immunofluorescence labelling of Cx43 with several different antibodies was widely distributed throughout the pineal, whereas another connexin examined, connexin26, was not found in pineal but only in surrounding leptomeninges. Labelling apparently associated with plasma membranes was visualized either as fine Cx43-puncta (1-2 μm) or as unusually large pools of Cx43 ranging up to 4-7 μm in diameter or length...
April 10, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28386236/metabolic-response-of-visceral-white-adipose-tissue-of-obese-mice-exposed-for-5-days-to-human-room-temperature-compared-to-mouse-thermoneutrality
#16
Inge van der Stelt, Femke Hoevenaars, Jitka Široká, Lidwien de Ronde, David Friedecký, Jaap Keijer, Evert van Schothorst
Housing of laboratory mice at room temperature (22°C) might be considered a constant cold stress, which induces a thermogenic program in brown adipose tissue (BAT). However, the early adaptive response of white adipose tissue (WAT), the fat storage organ of the body, to a change from thermoneutrality to room temperature is not known. This was investigated here for various WAT depots, focusing on epididymal WAT (eWAT), widely used as reference depot. Male adult diet-induced obese (DIO) C57BL/6JOlaHsd mice housed at thermoneutrality (29°C), were for 5 days either switched to room temperature (22°C) or remained at thermoneutrality...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28385052/perinatal-ssri-exposure-permanently-alters-cerebral-serotonin-receptor-mrna-in-mice-but-does-not-impact-adult-behaviors
#17
Lauritz R Meyer, Benjamin Dexter, Cecilia Lo, Elizabeth Kenkel, Takahito Hirai, Robert D Roghair, Sarah E Haskell
PURPOSE: Associations have been made between maternal selective serotonin reuptake inhibitor (SSRI) use during pregnancy and altered behavior in offspring, including an increased risk of autism. Given the important role serotonin plays in behavior, we hypothesized SSRI exposure in the perinatal period would alter central serotonin receptor expression and program adult behaviors in mice. METHODS: Female mice were injected with sertraline or saline throughout pregnancy...
April 24, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28382568/telotristat-ethyl-first-global-approval
#18
Anthony Markham
Telotristat ethyl (Xermelo™) is a peripheral tryptophan hydroxylase (TPH) inhibitor that was developed by Lexicon Pharmaceuticals, Inc. for the treatment of carcinoid syndrome. Many neuroendocrine tumours secrete serotonin (5-HT) into the blood stream, resulting in a number of symptoms, notably diarrhoea. Telotristat ethyl inhibits TPH, thereby reducing the production of 5-HT. In February 2017, telotristat ethyl was approved in the USA for the treatment of carcinoid syndrome diarrhoea in combination with somatostatin analog (SSA) therapy in adults inadequately controlled by SSA therapy...
May 2017: Drugs
https://www.readbyqxmd.com/read/28349031/treadmill-exercise-improves-depression-like-symptoms-by-enhancing-serotonergic-function-through-upregulation-of-5-ht1a-expression-in-the-olfactory-bulbectomized-rats
#19
Mal-Soon Shin, Sang-Seo Park, Jae-Min Lee, Tae-Woon Kim, Young-Pyo Kim
The olfactory bulbectomy (OBX) is a well-known method inducing animal model of depression. Depression is associated with dysfunction of serotonin (5-hydroxytryptamine, 5-HT) system. In the present study, antidepressive effect of treadmill exercise was investigated using olfactory bulbectomized rats. After bilateral bulbectomy, the rats in the treadmill exercise groups were subjected to run on a treadmill for 30 min once a day during 28 days. Increased immobility time and decreased fast time in the forced swim test were observed in the olfactory bulbectomized rats...
February 2017: Journal of Exercise Rehabilitation
https://www.readbyqxmd.com/read/28342337/nice-guys-homozygocity-for-the-tph2-703g-t-rs4570625-minor-allele-promotes-low-aggressiveness-and-low-anxiety
#20
Kariina Laas, Evelyn Kiive, Jarek Mäestu, Mariliis Vaht, Toomas Veidebaum, Jaanus Harro
BACKGROUND: Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the synthesis of serotonin. We examined whether the TPH2 polymorphism -703G/T (rs4570625) is associated with aggressiveness and impulsivity, and the prevalence of psychiatric disorders, in a population-representative sample. METHODS: We used self and proxy reports on aggressive behaviour in the younger birth cohort of the longitudinal Estonian Children Personality, Behaviour and Health Study collected at age 25, and earlier collected impulsivity and related data of both ECPBHS cohorts...
March 19, 2017: Journal of Affective Disorders
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