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Kynurenin

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https://www.readbyqxmd.com/read/28108668/ultraviolet-and-yellow-reflectance-but-not-fluorescence-is-important-for-visual-discrimination-of-conspecifics-by-heliconius-erato
#1
Susan D Finkbeiner, Dmitry A Fishman, Daniel Osorio, Adriana D Briscoe
Toxic Heliconius butterflies have yellow hindwing bars that - unlike their closest relatives - reflect ultraviolet (UV) and long wavelength light, and also fluoresce. The pigment in the yellow scales is 3-hydroxy-DL-kynurenine (3-OHK), found also in the hair and scales of a variety of animals. In other butterflies like pierids with color schemes characterized by independent sources of variation in UV and human-visible yellow/orange, behavioral experiments have generally implicated the UV component as most relevant to mate choice...
January 20, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28107600/the-predictive-and-prognostic-role-of-serum-neopterin-and-tryptophan-breakdown-in-prostate-cancer
#2
Renate Pichler, Josef Fritz, Isabel Heidegger, Eberhard Steiner, Zoran Culig, Helmut Klocker, Dietmar Fuchs
The Interferon-gamma induced enzymes indoleamine 2,3-dioxygenase and GTP-cylohydrolase are key players in tumor immune escape mechanisms. We quantified serum levels of neopterin and tryptophan breakdown (tryptophan, kynurenine and kynurenine-to-tryptophan ratio) in addition to prostate-specific antigen (PSA) in newly diagnosed prostate cancer (PCa) patients (n=100) before radical prostatectomy (RP) as well as at time of biochemical recurrence (BCR) after RP (n=50) in comparison to healthy men (n=49). Effects of biomarkers on the risk of PCa diagnosis on transrectal biopsy, worse histopathological characteristics of the RP specimens and cancer-specific survival (CSS) after BCR were investigated...
January 20, 2017: Cancer Science
https://www.readbyqxmd.com/read/28098246/tryptophan-metabolite-activation-of-the-aryl-hydrocarbon-receptor-regulates-il-10-receptor-expression-on-intestinal-epithelia
#3
J M Lanis, E E Alexeev, V F Curtis, D A Kitzenberg, D J Kao, K D Battista, M E Gerich, L E Glover, D J Kominsky, S P Colgan
IL-10 is a potent anti-inflammatory cytokine that inhibits the production of proinflammatory mediators. Signaling by IL-10 occurs through the IL-10 receptor (IL-10R), which is expressed in numerous cell types, including intestinal epithelial cells (IECs), where it is associated with development and maintenance of barrier function. Guided by an unbiased metabolomics screen, we identified tryptophan (Trp) metabolism as a major modifying pathway in interferon-γ (IFNγ)-dominant murine colitis. In parallel, we demonstrated that IFNγ induction of indoleamine 2,3-dioxygenase 1, an enzyme that catalyzes the conversion of Trp to kynurenine (Kyn), induces IL-10R1 expression...
January 18, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28097769/high-resolution-crystal-structures-of-human-kynurenine-aminotransferase-i-bound-to-plp-cofactor-and-in-complex-with-aminooxyacetate
#4
Naveed A Nadvi, Noeris K Salam, Joohong Park, Fady N Akladios, Vimal Kapoor, Charles A Collyer, Mark D Gorrell, And W Bret Church
In this study we report two high-resolution structures of the pyridoxal 5' phosphate (PLP)-dependent enzyme kynurenine aminotransferase-I (KAT-I). One is the native structure with the cofactor in the PLP form bound to Lys247 with the highest resolution yet available for KAT-I at 1.28 Å resolution, and the other with the general PLP-dependent aminotransferase inhibitor, aminooxyacetate (AOAA) covalently bound to the cofactor at 1.54 Å. Only small conformational differences are observed in the vicinity of the aldimine (oxime) linkage with which the PLP forms the Schiff base with Lys247 in the 1...
January 18, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28078987/role-of-proinflammatory-cytokines-in-dopaminergic-system-disturbances-implications-for-anhedonic-features-of-mdd
#5
Zihang Pan, Joshua D Rosenblat, Walter Swardfager, Roger S McIntyre
Anhedonia, characterized by a loss of interest and/or pleasure in previously enjoyable activities, is an important diagnostic criterion of Major Depressive Disorder (MDD). Converging evidence implicates a behaviouralcausal relationship between proinflammatory cytokines and disturbances that characterize anhedonia in the context of MDD. Additionally, anhedonia has been implicated in disturbances of key central dopaminergic modulatory pathways. Emerging research into the roles of tetrahydrobiopterin, a cytokine-targeted co-enzyme in the synthesis of dopamine, and kynurenine, a product of inflammation-sensitive breakdown of tryptophan via indoleamine 2, 3-dioxygenase, have shed new light into the role of inflammation in mediating anhedonic behaviours...
January 11, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28076309/activation-of-the-tryptophan-serotonin-pathway-is-associated-with-severity-and-predicts-outcomes-in-pneumonia-results-of-a-long-term-cohort-study
#6
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: As part of the immune defense during infection, an increase in enzyme activity of indoleamine 2,3-dioxygenase (IDO) leads to a breakdown of tryptophan to kynurenine. In previous animal studies, therapeutic antagonism of IDO resulted in reduced sepsis mortality. We investigated the prognostic ability of tryptophan, serotonin, kynurenine and IDO (represented by the ratio of kynurenine/tryptophan) to predict adverse clinical outcomes in patients with community-acquired pneumonia (CAP)...
January 11, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28071717/tryptophan-and-non-tryptophan-fluorescence-of-the-eye-lens-proteins-provides-diagnostics-of-cataract-at-the-molecular-level
#7
Anna Gakamsky, Rory R Duncan, Nicola M Howarth, Baljean Dhillon, Kim K Buttenschön, Daniel J Daly, Dmitry Gakamsky
The chemical nature of the non-tryptophan (non-Trp) fluorescence of porcine and human eye lens proteins was identified by Mass Spectrometry (MS) and Fluorescence Steady-State and Lifetime spectroscopy as post-translational modifications (PTM) of Trp and Arg amino acid residues. Fluorescence intensity profiles measured along the optical axis of human eye lenses with age-related nuclear cataract showed increasing concentration of fluorescent PTM towards the lens centre in accord with the increased optical density in the lens nucleolus...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28065794/adjuvant-quercetin-therapy-for-combined-treatment-of-epilepsy-and-comorbid-depression
#8
Tanveer Singh, Taranjot Kaur, Rajesh Kumar Goel
Epilepsy is one of the major neurological disorders frequently associated with psychiatric disorders such as depression. The predisposition of tryptophan metabolism towards kynurenine pathway has been reported as one of the plausible reasons for association of depression in epilepsy. Hence, this study was envisaged to evaluate the dose dependent inhibition of indoleamine 2,3-dioxygenase (IDO) enzyme employing quercetin (screened employing in vitro method) with levetiracetam for combined management of epilepsy and comorbid depression...
January 5, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28058465/fish-oil-supplementation-attenuates-neuroinflammation-and-alleviates-depressive-like-behavior-in-rats-submitted-to-repeated-lipopolysaccharide
#9
Ruili Dang, Xueyuan Zhou, Mimi Tang, Pengfei Xu, Xiaoxue Gong, Yuanyuan Liu, Hongxiao Jiao, Pei Jiang
PURPOSE: Depression is frequently associated with inflammation, whereas omega-3 polyunsaturated fatty acids (PUFAs) primarily found in fish oil possess anti-inflammatory properties. Although converging studies suggest an antidepressant effect of PUFAs, there is limited evidence directly linking the neuro-immune modulating features of PUFAs to the antidepressant actions. METHODS: Therefore, we assessed the effects of fish oil (FO) supplementation on behavioral changes, inflammatory cytokine expression and oxidative reactions in frontal cortex and hippocampus of rats following repeated peripheral immune challenge by lipopolysaccharide (LPS) for 2 weeks (500 μg/kg every other day)...
January 5, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28057727/indoleamine-2-3-dioxygenase-activity-is-associated-with-regulatory-t-cell-response-in-acute-puumala-hantavirus-infection
#10
Tuisku-Tuulia Koivula, Anni Tuulasvaara, Iivo Hetemäki, Mikko Hurme, Satu Mäkelä, Jukka Mustonen, Antti Vaheri, T Petteri Arstila
High indoleamine 2,3-dioxygenase (IDO) activity is associated with clinically severe acute infection caused by Puumala hantavirus. The immunoregulatory effects of IDO can be mediated either through metabolic control of effector T cells, caused by depletion of the essential amino acid tryptophan, or intercellular signaling and activation of regulatory T cell responses. Here we have studied 24 patients with acute PUUV infection to distinguish between these possibilities. Maximum IDO activity showed a significant positive correlation with FOXP3 expression levels in regulatory T cells, a quantitative surrogate marker for suppressive capability...
January 5, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28053021/first-in-human-phase-1-study-of-the-oral-inhibitor-of-indoleamine-2-3-dioxygenase-1-epacadostat-incb024360-in-patients-with-advanced-solid-malignancies
#11
Gregory L Beatty, Peter J O'Dwyer, Jason Clark, Jack G Shi, Kevin J Bowman, Peggy Scherle, Robert C Newton, Richard Schaub, Janet Maleski, Lance Leopold, Thomas F Gajewski
PURPOSE: Indoleamine 2,3-dioxygenase-1 (IDO1) catalyzes the degradation of tryptophan to N-formyl-kynurenine. Overexpressed in many solid malignancies, IDO1 can promote tumor escape from host immunosurveillance. This first-in-human phase 1 study investigated the maximum tolerated dose, safety, pharmacokinetics, pharmacodynamics, and antitumor activity of epacadostat (INCB024360), a potent and selective inhibitor of IDO1. PATIENTS AND METHODS: Fifty-two patients with advanced solid malignancies were treated with epacadostat (50 mg once daily or 50, 100, 300, 400, 500, 600, or 700 mg twice daily [BID]) in a dose-escalation 3 + 3 design and evaluated in 28-day cycles...
January 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28042675/1%C3%A2-h-nmr-based-metabolomics-study-for-identifying-urinary-biomarkers-and-perturbed-metabolic-pathways-associated-with-severity-of-iga-nephropathy-a-pilot-study
#12
Shiva Kalantari, Mohsen Nafar, Shiva Samavat, Mahmoud Parvin
The severity of IgA nephropathy (IgAN), the most common primary glomerulonephritis, is judged on the basis of histologic and clinical features. A limited number of studies have considered molecular signature of IgAN for this issue and no reliable biomarkers have been presented non-invasively for use in patient evaluations. This study aims to identify metabolite markers excreted in the urine and impaired pathways that are associated with a known marker of severity (proteinuria) to predict mild and severe stages of IgAN...
January 1, 2017: Magnetic Resonance in Chemistry: MRC
https://www.readbyqxmd.com/read/28017129/kynurenine-system-and-multiple-sclerosis-pathomechanism-and-drug-targets-with-an-emphasis-on-laquinimod
#13
Zsófia Majláth, Ádám Annus, László Vécsei
Multiple sclerosis is a common chronic, disabling autoimmune neurological disease affecting mainly young adults. In its pathomechanism, neurodegenerative and acute inflammatory characteristics are both involved. Disease-modifying therapies aim to reduce relapse-rate and slow down the deterioration in neurological functions. The currently available therapies fail to exert neuroprotective effects and most of them are associated with potentially toxic side-effects, therefore, ongoing research aims to develop novel drug candidates to cover these therapeutic gaps...
December 23, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/28013248/kynurenine-pathway-activation-in-human-african-trypanosomiasis
#14
Jeremy M Sternberg, Caroline M Forrest, R Neil Dalton, Charles Turner, Jean Rodgers, Trevor W Stone, Peter Ge Kennedy
BACKGROUND: The kynurenine pathway of tryptophan oxidation is associated with CNS inflammatory pathways. Inhibition of this pathway ameliorates CNS inflammation in rodent models of the late (meningoencephalitic) stage of Human African trypanosomiasis (HAT). In this study we evaluate whether the kynurenine pathway is activated in clinical HAT and if it is associated with CNS inflammatory responses. METHODS: We measured cerebrospinal fluid (CSF) tryptophan and kynurenine metabolite concentrations in Trypanosoma brucei rhodesiense patients using liquid chromatography-mass spectrometry...
December 24, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28005163/intratumoral-th2-predisposition-combines-with-an-increased-th1-functional-phenotype-in-clinical-response-to-intravesical-bcg-in-bladder-cancer
#15
Renate Pichler, Georg Gruenbacher, Zoran Culig, Andrea Brunner, Dietmar Fuchs, Josef Fritz, Hubert Gander, Andrea Rahm, Martin Thurnher
Th1-type immunity is considered to be required for efficient response to BCG in bladder cancer, although Th2 predisposition of BCG responders has recently been reported. The aim was to evaluate the relationship of Th1 and Th2 components in 23 patients undergoing BCG treatment. Peripheral blood, serum and urine samples were prospectively collected at baseline, during and after BCG. Th1 (neopterin, tryptophan, kynurenine, kynurenine-to-tryptophan ratio (KTR), IL-12, IFN-γ, soluble TNF-R75 and IL-2Rα) and Th2 (IL-4, IL-10) biomarkers as well as CD4 expression in T helper (Th), effector and regulatory T cells were determined...
December 22, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28004656/co-delivery-of-indoleamine-2-3-dioxygenase-prevents-loss-of-expression-of-an-antigenic-transgene-in-dystrophic-mouse-muscles
#16
D Sharma, R Al-Khalidi, S Edgar, Q An, Y Wang, C Young, D Nowis, D C Gorecki
A significant problem affecting gene therapy approaches aiming at achieving long-term transgene expression is the immune response against the protein product of the therapeutic gene, which can reduce or eliminate the therapeutic effect. The problem is further exacerbated when therapy involves targeting an immunogenic tissue and/or one with a pre-existing inflammatory phenotype, such as dystrophic muscles. In this proof-of-principle study, we co-expressed a model antigen, bacterial β-galactosidase, with an immunosuppressive factor, indoleamine 2,3-dioxygenase 1 (IDO1), in muscles of the mdx mouse model of Duchenne muscular dystrophy...
December 22, 2016: Gene Therapy
https://www.readbyqxmd.com/read/28003141/identification-and-optimization-of-a-novel-series-of-indoleamine-2-3-dioxygenase-inhibitors
#17
Jay A Markwalder, Steven P Seitz, Yuval Blat, Lisa Elkin, John T Hunt, Jonathan G Pabalan, Maria N Jure-Kunkel, Gregory D Vite, Kelly Covello
The discovery of a series of structurally-novel biaryl urea IDO inhibitors is described. Optimization of a micromolar hit through iterative cycles of synthesis and screening in an assay measuring IDO-mediated intracellular conversion of tryptophan to kynurenine led to potent inhibitors with favorable selectivity and metabolic stability profiles.
December 7, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27995942/improvement-in-detrusor-sphincter-dyssynergia-by-bladder-wall-injection-of-replication-defective-herpes-simplex-virus-vector-mediated-gene-delivery-of-kynurenine-aminotransferase-ii-in-spinal-cord-injury-rats
#18
Z Wang, L Liao
STUDY DESIGN: An experimental study. OBJECTIVES: To investigate the effect of replication-defective herpes simplex virus (HSV) vectors encoding the kynurenine aminotransferase II (HSVrd-KATII) gene on detrusor-sphincter dyssynergia (DSD) in spinal cord injury (SCI) rats. SETTING: Beijing, China. METHODS: Sprague-Dawley rats (240-265 g) were spinalized with complete transaction at the T10 level of the spinal cord. The rats were randomly divided into the following three groups: sham group (n=12, with normal saline); HSVrd group (n=12, with HSVrd) and HSVrd-KATII group (n=12, with HSVrd-KATII)...
December 20, 2016: Spinal Cord
https://www.readbyqxmd.com/read/27994758/fused-heterocyclic-compounds-as-potent-indoleamine-2-3-dioxygenase-1-inhibitors
#19
Subhankar Panda, Ashalata Roy, Suman Jyoti Deka, Vishal Trivedi, Debasis Manna
Uncontrolled metabolism of l-tryptophan (l-Trp) in the immune system has been recognized as a critical cellular process in immune tolerance. Indoleamine 2,3-dioxygenase 1 (IDO1) enzyme plays an important role in the metabolism of a local l-Trp through the kynurenine pathway in the immune systems. In this regard, IDO1 has emerged as a therapeutic target for the treatment of diseases that are associated with immune suppression like chronic infections, cancer, and others. In this study, we synthesized a series of pyridopyrimidine, pyrazolopyranopyrimidine, and dipyrazolopyran derivatives...
December 8, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27994058/signal-transducer-and-activator-of-transcription-1-plays-a-pivotal-role-in-ret-ptc3-oncogene-induced-expression-of-indoleamine-2-3-dioxygenase-1
#20
Sonia Moretti, Elisa Menicali, Nicole Nucci, Pasquale Voce, Renato Colella, Rosa Marina Melillo, Federica Liotti, Silvia Morelli, Francesca Fallarino, Antonio Macchiarulo, Massimo Santoro, Nicola Avenia, Efisio Puxeddu
Indoleamine 2,3-dioxygenase 1 (IDO1) is a single chain oxidoreductase that catalyzes tryptophan degradation to kynurenine. In cancer, it exerts an immunosuppressive function as part of an acquired mechanism of immune-escape. Recently, we demonstrated that IDO1 expression is significantly higher in all thyroid cancer histotypes compared to normal thyroid and that its expression levels correlate with T regulatory (Treg) lymphocyte densities in the tumor microenvironment. BRAFV600E- and RET/PTC3-expressing PcCL3 cells were used as cellular models for the evaluation of IDO1 expression in thyroid carcinoma cells and for the study of involved signal transduction pathways...
December 19, 2016: Journal of Biological Chemistry
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