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https://www.readbyqxmd.com/read/28424186/circulating-concentrations-of-biomarkers-and-metabolites-related-to-vitamin-status-one-carbon-and-the-kynurenine-pathways-in-us-nordic-asian-and-australian-populations
#1
Øivind Midttun, Despoina Theofylaktopoulou, Adrian McCann, Anouar Fanidi, David C Muller, Klaus Meyer, Arve Ulvik, Wei Zheng, Xiao-Ou Shu, Yong-Bing Xiang, Ross Prentice, Cynthia A Thomson, Mary Pettinger, Graham G Giles, Allison Hodge, Qiuyin Cai, William J Blot, Jie Wu, Mikael Johansson, Johan Hultdin, Kjell Grankvist, Victoria L Stevens, Marjorie L McCullough, Stephanie J Weinstein, Demetrius Albanes, Arnulf Langhammer, Kristian Hveem, Marit Næss, Howard D Sesso, J Michael Gaziano, Julie E Buring, I-Min Lee, Gianluca Severi, Xuehong Zhang, Jiali Han, Meir J Stampfer, Stephanie A Smith-Warner, Anne Zeleniuch-Jacquotte, Loic le Marchand, Jian-Min Yuan, Lesley M Butler, Woon-Puay Koh, Renwei Wang, Yu-Tang Gao, Ulrika Ericson, Emily Sonestedt, Regina G Ziegler, Neal D Freedman, Kala Visvanathan, Miranda R Jones, Caroline Relton, Paul Brennan, Mattias Johansson, Per M Ueland
Background: Circulating concentrations of biomarkers that are related to vitamin status vary by factors such as diet, fortification, and supplement use. Published biomarker concentrations have also been influenced by the variation across laboratories, which complicates a comparison of results from different studies.Objective: We robustly and comprehensively assessed differences in biomarkers that are related to vitamin status across geographic regions.Design: The trial was a cross-sectional study in which we investigated 38 biomarkers that are related to vitamin status and one-carbon and tryptophan metabolism in serum and plasma from 5314 healthy control subjects representing 20 cohorts recruited from the United States, Nordic countries, Asia, and Australia, participating in the Lung Cancer Cohort Consortium...
April 19, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28412922/abnormalities-in-kynurenine-pathway-metabolism-in-treatment-resistant-depression-and-suicidality-a-systematic-review
#2
Gianluca Serafini, Giulia Adavastro, Giovanna Canepa, Laura Capobianco, Claudia Conigliaro, Federica Pittaluga, Martino Belvederi Murri, Alessandro Valchera, Domenico De Berardis, Maurizio Pompili, Daniel Lindqvist, Lena Brundin, Mario Amore
Treatment resistant depression (TRD) and suicidal behavior are among the most important public health problems and are commonly associated with significant disability and psychosocial impairment. Although there have been recent advances in identifying neurobiological correlates of these complex conditions, their pathophysiology still remains unclear. Although the recent advances concerning the neurobiological determinants underlying these complex conditions, their pathophysiology still remains unclear. Compared to non-suicidal subjects, higher mean concentrations of inflammatory mediators have been found in both the periphery and brain of individuals at risk for suicide...
April 13, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28407315/drugs-with-antidepressant-properties-affect-tryptophan-metabolites-differently-in-rodent-models-with-depression-like-behavior
#3
Amanda Eskelund, Yan Li, David P Budac, Heidi K Müller, Gulinello Maria, Connie Sanchez, Gregers Wegener
The metabolism of tryptophan through kynurenine and serotonin pathways is linked to depression. Here, effects of different drugs with antidepressant properties (vortioxetine, fluoxetine and ketamine) on various tryptophan metabolites in different brain regions and plasma were examined using tandem mass spectrometry (LC-MS/MS), in Flinders Sensitive Line (FSL) rats, a genetic rat model of depression, and its controls: Flinders Resistant Line (FRL) and Sprague-Dawley (SD) rats. Protein levels of kynurenine pathway enzymes were measured in the brains and livers of these rat strains...
April 13, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28402179/antiviral-effect-of-ido-in-mouse-fibroblast-cells-during-influenza-virus-infection
#4
Fang Li, Håkan Karlsson
While upregulation of 2,3-dioxygenase (IDO) accompanied by degradation of tryptophan along the kynurenine pathway have been reported to exert antimicrobial effects against a wide range of infectious agents, its role in the replication of influenza A virus remains uncertain. We performed experiments using influenza A/WSN/33 virus infection of mouse fibroblast cell-line (NIH-3T3) to study the effects of IDO on viral replication. Influenza infection resulted in prominent elevations of transcripts encoding IDO, interferon (IFN)-β, and segment 8 of the virus in NIH-3T3 cells...
April 12, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28400091/metabolomic-changes-demonstrate-reduced-bioavailability-of-tyrosine-and-altered-metabolism-of-tryptophan-via-the-kynurenine-pathway-with-ingestion-of-medical-foods-in-phenylketonuria
#5
Denise M Ney, Sangita G Murali, Bridget M Stroup, Nivedita Nair, Emily A Sawin, Fran Rohr, Harvey L Levy
BACKGROUND: Deficiencies of the monoamine neurotransmitters, such as dopamine synthesized from Tyr and serotonin synthesized from Trp, are of concern in PKU. Our objective was to utilize metabolomics analysis to assess monoamine metabolites in subjects with PKU consuming amino acid medical foods (AA-MF) and glycomacropeptide medical foods (GMP-MF). METHODS: Subjects with PKU consumed a low-Phe diet combined with AA-MF or GMP-MF for 3weeks each in a randomized, controlled, crossover study...
April 6, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28398245/molecular-targets-for-pet-imaging-of-activated-microglia-the-current-situation-and-future-expectations
#6
REVIEW
Claire Tronel, Bérenger Largeau, Maria Joao Santiago Ribeiro, Denis Guilloteau, Anne-Claire Dupont, Nicolas Arlicot
Microglia, as cellular mediators of neuroinflammation, are implicated in the pathogenesis of a wide range of neurodegenerative diseases. Positron emission tomography (PET) imaging of microglia has matured over the last 20 years, through the development of radiopharmaceuticals targeting several molecular biomarkers of microglial activation and, among these, mainly the translocator protein-18 kDa (TSPO). Nevertheless, current limitations of TSPO as a PET microglial biomarker exist, such as low brain density, even in a neurodegenerative setting, expression by other cells than the microglia (astrocytes, peripheral macrophages in the case of blood brain barrier breakdown), genetic polymorphism, inducing a variation for most of TSPO PET radiopharmaceuticals' binding affinity, or similar expression in activated microglia regardless of its polarization (pro- or anti-inflammatory state), and these limitations narrow its potential interest...
April 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28377795/crosstalk-between-tryptophan-metabolism-and-cardiovascular-disease-mechanisms-and-therapeutic-implications
#7
REVIEW
Gang Liu, Shuai Chen, Jin Zhong, Kunling Teng, Yulong Yin
The cardiovascular diseases (CVD) associated with the highest rates of morbidity are coronary heart disease and stroke, and the primary etiological factor leading to these conditions is atherosclerosis. This long-lasting inflammatory disease, characterized by how it affects the artery wall, results from maladaptive immune responses linked to the vessel wall. Tryptophan (Trp) is oxidized in a constitutive manner by tryptophan 2,3-dioxygenase in liver cells, and for alternative cell types, it is catalyzed in the presence of a differently inducible indoleamine 2,3-dioxygenase (IDO1) in the context of a specific pathophysiological environment...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28376401/controversial-alkoxyl-and-peroxyl-radical-scavenging-activity-of-the-tryptophan-metabolite-3-hydroxy-anthranilic-acid
#8
E Dorta, A Aspée, E Pino, L González, E Lissi, C López-Alarcón
3-Hydroxy-anthranilic acid (3-OHAA), a tryptophan metabolite produced in the kynurenine pathway, is an efficient antioxidant towards peroxyl radicals (ROO) derived from the AAPH (2,2'-azobis(2-amidinopropane) dihydrochloride) thermolysis. However, self-reactions of ROO can give rise to alkoxyl radicals (RO), which could strongly affect the fate of scavenging reactions. In the present work, we studied the influence of RO in the scavenging activity of 3-OHAA in three different systems: i) Monitoring of the direct reaction between 3-OHAA and AAPH-derived free radicals (kinetic studies); ii) Evaluation of the protective effect of 3-OHAA on the AAPH-induced consumption of fluorescein; and, iii) Inhibition, given by 3-OHAA, of the AAPH-initiated lipid peroxidation of both, rat brain synaptosomes and homogenate preparations (assessed by chemiluminescence)...
April 1, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28375145/crystal-structures-of-human-3-hydroxyanthranilate-3-4-dioxygenase-with-native-and-non-native-metals-bound-in-the-active-site
#9
Lakshmi Swarna Mukhi Pidugu, Heather Neu, Tin Lok Wong, Edwin Pozharski, John L Molloy, Sarah L J Michel, Eric A Toth
3-Hydroxyanthranilate 3,4-dioxygenase (3HAO) is an enzyme in the microglial branch of the kynurenine pathway of tryptophan degradation. 3HAO is a non-heme iron-containing, ring-cleaving extradiol dioxygenase that catalyzes the addition of both atoms of O2 to the kynurenine pathway metabolite 3-hydroxyanthranilic acid (3-HANA) to form quinolinic acid (QUIN). QUIN is a highly potent excitotoxin that has been implicated in a number of neurodegenerative conditions, making 3HAO a target for pharmacological downregulation...
April 1, 2017: Acta Crystallographica. Section D, Structural Biology
https://www.readbyqxmd.com/read/28359744/activation-of-the-kynurenine-pathway-predicts-poor-outcome-in-patients-with-clear-cell-renal-cell-carcinoma
#10
Giuseppe Lucarelli, Monica Rutigliano, Matteo Ferro, Andrea Giglio, Angelica Intini, Francesco Triggiano, Silvano Palazzo, Margherita Gigante, Giuseppe Castellano, Elena Ranieri, Carlo Buonerba, Daniela Terracciano, Francesca Sanguedolce, Anna Napoli, Eugenio Maiorano, Franco Morelli, Pasquale Ditonno, Michele Battaglia
OBJECTIVE: To investigate the expression of the kynurenine (KYN) pathway components and the prognostic role of the KYN-to-tryptophan ratio (KTR) in a cohort of patients with clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: The expression of KYN pathway components was investigated by tissue microarray-based immunohistochemistry, indirect immunofluorescence, and confocal microscopy analysis in 100 ccRCC cases and 30 normal renal samples. The role of this pathway in sustaining cancer cell proliferation, migration, and chemoresistance was evaluated...
March 27, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28357780/targeting-tdo-in-cancer-immunotherapy
#11
REVIEW
Cheng-Peng Yu, Yun-Lei Song, Zheng-Ming Zhu, Bo Huang, Ying-Qun Xiao, Da-Ya Luo
Tryptophan-2,3-dioxygenase (TDO) is a homotetrameric heme-containing protein catalyzing the initial step in the kynurenine pathway, which oxidates the 2,3-double bond of the indole ring in L-tryptophan and catalyzes it into kynurenine (KYN). The upregulation of TDO results in a decrease in tryptophan and the accumulation of KYN and its metabolites. These metabolites can affect the proliferation of T cells. Increasing evidence demonstrates that TDO is a promising therapeutic target in the anti-tumor process...
May 2017: Medical Oncology
https://www.readbyqxmd.com/read/28320838/early-immune-regulatory-changes-in-a-primary-controlled-human-plasmodium-vivax-infection-cd1c-mdc-maturation-arrest-induction-of-the-kynurenine-pathway-and-regulatory-t-cell-activation
#12
Tonia Woodberry, Jessica R Loughland, Gabriela Minigo, Julie G Burel, Fiona H Amante, Kim A Piera, Yvette McNeil, Tsin W Yeo, Michael F Good, Denise L Doolan, Christian R Engwerda, James S McCarthy, Nicholas M Anstey
Plasmodium vivax malaria remains a major public health problem. The requirements for acquisition of protective immunity to this species are not clear. Dendritic cells (DC) are essential for immune cell priming, but also perform immune-regulatory functions, along with regulatory T cells (Treg). An important function of DC involves activation of the kynurenine pathway via indoleamine 2,3-dioxygenase (IDO). Using a controlled human experimental infection study with blood-stage P. vivax, we characterised plasmacytoid DC (pDC) and myeloid DC (mDC) subset maturation, CD4(+)CD25(+)CD127(lo) Treg activation and IDO activity...
March 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28319697/genetic-variants-of-the-kynurenine-3-monooxygenase-and-postpartum-depressive-symptoms-after-cesarean-section-in-chinese-women
#13
Sai-Ying Wang, Kai-Ming Duan, Xiao-Fang Tan, Ji-Ye Yin, Xiao-Yuan Mao, Wei Zheng, Chun-Yan Wang, Mi Yang, Cheng Peng, Hong-Hao Zhou, Zhao-Qian Liu
BACKGROUND: New conceptualizations of depression have emphasized the role of the kynurenine pathway (KP) in the pathogenesis of postpartum depressive symptoms (PDS). Kynurenine 3-monooxygenase (KMO) is a rate-limiting enzyme of the KP, where it catalyzes the conversion of kynurenine (KYN) to 3-hydroxykynurenine (3-HK). Previous work indicates that KMO is closely linked to the pathophysiology of depressive disorders. The purpose of this study is to investigate whether variations in the KMO gene affect PDS development after cesarean section...
March 10, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28314892/abnormal-kynurenine-pathway-of-tryptophan-catabolism-in-cardiovascular-diseases
#14
REVIEW
Ping Song, Tharmarajan Ramprasath, Huan Wang, Ming-Hui Zou
Kynurenine pathway (KP) is the primary path of tryptophan (Trp) catabolism in most mammalian cells. The KP generates several bioactive catabolites, such as kynurenine (Kyn), kynurenic acid (KA), 3-hydroxykynurenine (3-HK), xanthurenic acid (XA), and 3-hydroxyanthranilic acid (3-HAA). Increased catabolite concentrations in serum are associated with several cardiovascular diseases (CVD), including heart disease, atherosclerosis, and endothelial dysfunction, as well as their risk factors, including hypertension, diabetes, obesity, and aging...
March 17, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28303855/expression-and-prognostic-value-of-indoleamine-2-3-dioxygenase-in-pancreatic-cancer
#15
Tao Zhang, Xiang-Long Tan, Yong Xu, Zi-Zheng Wang, Chao-Hui Xiao, Rong Liu
BACKGROUND: Indoleamine 2,3-dioxygenase (IDO), an enzyme for tryptophan metabolism through the kynurenine pathway, exhibits an immunosuppressive effect and induces immune tolerance in tumor cells. The effects of IDO on pancreatic cancer are poorly understood. This study aimed to investigate the expression and prognostic significance of IDO in pancreatic cancer. METHODS: We evaluated the protein expression of IDO in PANC-1, CFPAC-1, and BxPC-3 cell lines with or without 48 h treatment by 500 U/ml interferon-γ (IFN-γ)...
March 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28275903/correlations-of-kynurenic-acid-3-hydroxykynurenine-sil-2r-ifn-%C3%AE-and-il-4-with-clinical-symptoms-during-acute-relapse-of-schizophrenia
#16
Kinga Szymona, Barbara Zdzisińska, Hanna Karakuła-Juchnowicz, Tomasz Kocki, Martyna Kandefer-Szerszeń, Marta Flis, Wojciech Rosa, Ewa M Urbańska
Several lines of evidence suggest that up-regulation of immune response and alterations of kynurenine pathway function are involved in pathogenesis of schizophrenia. Correlations among clinical status (using PANNS, SANS and SAPS scales) and blood levels of kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK) and levels of selected immunoactive molecules, soluble interleukin-2 receptor (sIL-2R), interferon-α (IFN-α) and IL-4 were analyzed in 51 chronic schizophrenia patients during acute relapse, after four weeks of therapy and at remission...
March 8, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28250737/kynurenine-pathway-metabolism-and-neuroinflammatory-disease
#17
REVIEW
Nady Braidy, Ross Grant
Immune-mediated activation of tryptophan (TRYP) catabolism via the kynurenine pathway (KP) is a consistent finding in all inflammatory disorders. Several studies by our group and others have examined the neurotoxic potential of neuroreactive TRYP metabolites, including quinolinic acid (QUIN) in neuroinflammatory neurological disorders, including Alzheimer's disease (AD), multiple sclerosis, amylotropic lateral sclerosis (ALS), and AIDS related dementia complex (ADC). Our current work aims to determine whether there is any benefit to the affected individuals in enhancing the catabolism of TRYP via the KP during an immune response...
January 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28238935/tryptophan-and-purine-metabolites-are-consistently-upregulated-in-the-urinary-metabolome-of-patients-diagnosed-with-gestational-diabetes-mellitus-throughout-pregnancy-a-longitudinal-metabolomics-study-of-chinese-pregnant-women-part-2
#18
Kai P Law, Ting-Li Han, Xun Mao, Hua Zhang
BACKGROUND: Gestational diabetes mellitus (GDM) is a pathological state of glucose intolerance associated with adverse pregnancy outcomes and an increased risk of developing maternal type 2 diabetes later in life. The mechanisms underlying GDM development are not fully understood. We examined the pathophysiology of GDM through comprehensive metabolic profiling of maternal urine, using participants from a longitudinal cohort of normal pregnancies and pregnancies complicated by GDM. METHODS: Based on ultra-performance liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry, an untargeted metabolomics study was performed to explore the differences in the urinary metabolome of GDM cases and healthy controls over the course of pregnancy...
February 24, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28223212/n-butylidenephthalide-exhibits-protection-against-neurotoxicity-through-regulation-of-tryptophan-2-3-dioxygenase-in-spinocerebellar-ataxia-type-3
#19
Karthyayani Rajamani, Jen-Wei Liu, Cheng-Han Wu, I-Tsang Chiang, Deng-Huwei You, Si-Yin Lin, Dean-Kuo Hsieh, Shinn-Zong Lin, Horng-Jyh Harn, Tzyy-Wen Chiou
Spinocerebellar ataxia type 3 or Machado-Joseph disease (SCA3/MJD) is characterized by the repetition of a CAG codon in the ataxin-3 gene (ATXN3), which leads to the formation of an elongated mutant ATXN3 protein that can neither be denatured nor undergo proteolysis in the normal manner. This abnormal proteolysis leads to the accumulation of cleaved fragments, which have been identified as toxic and further they act as a seed for more aggregate formation, thereby increasing toxicity in neuronal cells. To date, there have been few studies or treatment strategies that have focused on controlling toxic fragment formation...
February 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28212884/desipramine-decreases-expression-of-human-and-murine-indoleamine-2-3-dioxygenases
#20
Alexandra K Brooks, Tiffany M Janda, Marcus A Lawson, Jennifer L Rytych, Robin A Smith, Cecilia Ocampo-Solis, Robert H McCusker
Abundant evidence connects depression symptomology with immune system activation, stress and subsequently elevated levels of kynurenine. Anti-depressants, such as the tricyclic norepinephrine/serotonin reuptake inhibitor desipramine (Desip), were developed under the premise that increasing extracellular neurotransmitter level was the sole mechanism by which they alleviate depressive symptomologies. However, evidence suggests that anti-depressants have additional actions that contribute to their therapeutic potential...
May 2017: Brain, Behavior, and Immunity
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