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Tryptophan catabolism

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https://www.readbyqxmd.com/read/28414589/progesterone-decreases-in-vitro-indoleamine-2-3-dioxygenase-expression-in-dendritic-and-cd4-cells-from-maternal-fetal-interface-of-rats
#1
Pedro Kastein Faria da Cunha Bianchi, Rafael Magdanelo Leandro, Aline Nayara Poscai, Tulio Yoshinaga, Patrícia Orlandini Gonçalez, José Roberto Kfoury Junior
PROBLEM: Several mechanisms contribute to the tolerogenic state observed during pregnancy, such as the activity of the enzyme indoleamine 2, 3-dioxygenase (IDO). This initializes the catabolism of tryptophan, inducing T cells to apoptosis due to its deprivation and by the action of its catabolites in the placental microenvironment. Progesterone plays an important part on immunological tolerance mechanisms during pregnancy; however, there is no evidence it is related to IDO activity. Thus, this study aimed to investigate progesterone influence on the maternal-fetal interface of pregnant Wistar rats, by identifying IDO positive cells by immunophenotyping and flow cytometry under exogenous progesterone supplementation...
April 17, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28411331/glutaric-acidemia-type-1-a-case-of-infantile-stroke
#2
Gül Demet Kaya Ozcora, Songul Gokay, Mehmet Canpolat, Fatih Kardaş, Mustafa Kendirci, Sefer Kumandaş
BACKGROUND: Glutaric acidemia Type 1 (GA-1) is an autosomal recessively inherited metabolic disorder which is associated with GCDH gene mutations which alters the glutaryl-CoA dehydrogenase, an enzyme playing role in the catabolic pathways of the amino acids lysine, hydroxylysine, and tryptophan. Clinical findings are often encephalopathic crises, dystonia, and extrapyramidal symptoms. CASE REPORT: A 9-month-old male infant referred to our department with focal tonic-clonic seizures during rotavirus infection and acute infarcts in MRI...
April 15, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28405495/biological-and-clinical-significance-of-tryptophan-catabolizing-enzymes-in-cutaneous-t-cell-lymphomas
#3
Pilvi Maliniemi, Kirsi Laukkanen, Liisa Väkevä, Katja Dettmer, Tuomas Lipsanen, Leila Jeskanen, Alban Bessede, Peter J Oefner, Marshall E Kadin, Annamari Ranki
Indoleamine 2,3-deoxygenase 1 (IDO1) induces immune tolerance in the tumor microenvironment (TME) and is recognized as a potential therapeutic target. We studied the expression of both IDO1 and the related tryptophan 2,3-dioxygenase (TDO) in several different subtypes of cutaneous T-cell lymphoma (CTCL), and evaluated the kynurenine (KYN) pathway in the local TME and in patient sera. Specimens from the total of 90 CTCL patients, including mycosis fungoides (MF, n = 37), lymphomatoid papulosis (LyP, n = 36), primary cutaneous anaplastic large cell lymphoma (pcALCL, n = 4), subcutaneous panniculitis-like T-cell lymphoma (SPTCL n = 13), and 10 patients with inflammatory lichen ruber planus (LRP), were analyzed by immunohistochemistry (IHC), immunofluorescence (IF), quantitative PCR, and/or liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28395446/-tryptophan-metabolism-in-patients-with-primary-immune-thrombocytopenia-with-high-dose-of-dexamethasone
#4
Z J Li, X Q Liu, J Q Xu, Y H Liu, L M Chen, X X Chu
Objective: To test whether the tryptophan metabolism was abnormal in newly diagnosed ITP patients as well as in these patients after treatment with dexamethasone. Methods: Newly diagnosed patients with ITP between Jan 2014 and May 2015 were enrolled, including 14 females and 11 males, with a median age of 57 years and a median PLT count of 16 (0-32) ×10(9)/L. All patients were treated with oral dexamethasone. The expression levels of IDO mRNA and TTS mRNA in peripheral blood mononuclear cells (PBMC) were analyzed by real-time quantitative polymerase chain reaction...
March 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28367063/understanding-the-role-of-pd-l1-pd1-pathway-blockade-and-autophagy-in-cancer-therapy
#5
REVIEW
Marianela Robainas, Rafael Otano, Stephen Bueno, Sihem Ait-Oudhia
Autophagy is a vital, physiological catabolic process for cell survival by which cells clear damaged organelles and recycle nutrients when homeostasis is maintained. Cancer is a complex disease with uncontrolled growth of cancer cells. Recent studies have suggested the role of autophagy in cancer. A complex relationship exists between autophagy and cancer, since autophagy can contribute to the survival or the destruction of malignant cells depending on the stage of tumor development. In this review, we describe in detail the mechanism underlying autophagy in cancer cells and the intricate involvement of the programmed cell death-1 (PD1) receptor with its ligand (PD-L1)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28366444/tryptophan-and-kynurenine-levels-and-its-association-with-sleep-nonphysical-fatigue-and-depression-in-chronic-hemodialysis-patients
#6
Rakesh Malhotra, Vanja Persic, Weifang Zhang, Jill Brown, Xia Tao, Laura Rosales, Stephan Thijssen, Fredric O Finkelstein, Mark L Unruh, Alp Ikizler, Pranav S Garimella, Joachim H Ix, Jeroen Kooman, Nathan W Levin, Garry J Handelman, Peter Kotanko
OBJECTIVE: Sleep and mood disorders are common in hemodialysis (HD) patients and the pathophysiology is still unclear. Tryptophan (TRP) and its metabolites may play a prominent role in neural pathways related to sleep, fatigue, and depression. Here, we sought to compare the levels of TRP and its metabolites between HD patients and healthy subjects and examine their association with sleep, fatigue, and depression in HD patients. The design was cross-sectional analysis. SUBJECTS: Ninety-nine adult patients on stable thrice weekly HD schedule between September 2011 and March 2014 and 10 healthy controls...
March 30, 2017: Journal of Renal Nutrition
https://www.readbyqxmd.com/read/28344890/suppression-of-indoleamine-2-3-dioxygenase-1-expression-by-promoter-hypermethylation-in-er-positive-breast-cancer
#7
Dyah L Dewi, Soumya R Mohapatra, Saioa Blanco Cabañes, Isabell Adam, Luis F Somarribas Patterson, Bianca Berdel, Masroor Kahloon, Loreen Thürmann, Stefanie Loth, Katharina Heilmann, Dieter Weichenhan, Oliver Mücke, Ines Heiland, Pauline Wimberger, Jan Dominik Kuhlmann, Karl-Heinz Kellner, Sarah Schott, Christoph Plass, Michael Platten, Clarissa Gerhäuser, Saskia Trump, Christiane A Opitz
Kynurenine formation by tryptophan-catabolic indoleamine-2,3-dioxygenase 1 (IDO1) plays a key role in tumor immune evasion and inhibition of IDO1 is efficacious in preclinical models of breast cancer. As the response of breast cancer to immune checkpoint inhibitors may be limited, a better understanding of the expression of additional targetable immunomodulatory pathways is of importance. We therefore investigated the regulation of IDO1 expression in different breast cancer subtypes. We identified estrogen receptor α (ER) as a negative regulator of IDO1 expression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28314892/abnormal-kynurenine-pathway-of-tryptophan-catabolism-in-cardiovascular-diseases
#8
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/28264972/synovial-fibroblasts-selectively-suppress-th1-cell-responses-through-ido1-mediated-tryptophan-catabolism
#9
Lars-Oliver Tykocinski, Anna M Lauffer, Antonia Bohnen, Nathalie-Christin Kaul, Stefan Krienke, Theresa Tretter, Isabell Adam, Soumya R Mohapatra, Philippe Saikali, Max Löhning, Michel Neidhart, Steffen Gay, Iris Oezen, Michael Platten, Christiane A Opitz, Hanns-Martin Lorenz
The development of rheumatoid arthritis (RA) is linked to functional changes in synovial fibroblasts (SF) and local infiltration of T lymphocytes. Fibroblasts possess the capacity to suppress T cell responses, although the molecular mechanisms of this suppression remain incompletely understood. In this study, we aimed to define the mechanisms by which noninflammatory SF modulate Th cell responses and to determine the immunosuppressive efficacy of RASF. Hence, the influence of SF from osteoarthritis or RA patients on total Th cells or different Th cell subsets of healthy donors was analyzed in vitro...
March 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28250737/kynurenine-pathway-metabolism-and-neuroinflammatory-disease
#10
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
#11
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/28218981/the-genetic-architecture-of-amino-acids-dissection-by-association-and-linkage-analysis-in-maize
#12
Min Deng, Dongqin Li, Jingyun Luo, Yingjie Xiao, Haijun Liu, Qingchun Pan, Xuehai Zhang, Minliang Jin, Mingchao Zhao, Jianbing Yan
Amino acids are both constituents of proteins, providing the essential nutrition for humans and animals, and signaling molecules regulating the growth and development of plants. Most cultivars of maize are deficient in essential amino acids such as lysine and tryptophan. Here, we measured the levels of 17 different total amino acids, and created 48 derived traits in mature kernels from a maize diversity inbred collection and three recombinant inbred line (RIL) populations. By GWAS, 247 and 281 significant loci were identified in two different environments, 5...
February 20, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28196863/conformational-changes-in-the-activation-loop-of-mitochondrial-glutaminase-c-a-direct-fluorescence-readout-that-distinguishes-the-binding-of-allosteric-inhibitors-from-activators
#13
Clint A Stalnecker, Jon W Erickson, Richard A Cerione
The first step in glutamine catabolism is catalysis by the mitochondrial enzyme glutaminase, with a specific isoform, glutaminase C (GAC), being highly expressed in cancer cells. GAC activation requires the formation of homotetramers, promoted by anionic allosteric activators such as inorganic phosphate. This leads to the proper orientation of a flexible loop proximal to the dimer-dimer interface that is essential for catalysis (i.e. the "activation loop"). A major class of allosteric inhibitors of GAC, with the prototype being bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES) and the related molecule CB-839, binds to the activation loop and induces the formation of an inactive tetramer (two inhibitors bound per active tetramer)...
April 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28159919/evaluation-of-radiofluorinated-carboximidamides-as-potential-ido-targeted-pet-tracers-for-cancer-imaging
#14
Xuan Huang, Zhongjie Pan, Michael L Doligalski, Xia Xiao, Epifanio Ruiz, Mikalai M Budzevich, Haibin Tian
IDO1 is an enzyme catalyzing the initial and rate-limiting step in the catabolism of tryptophan along the kynurenine pathway. IDO1 expression could suppress immune responses by blocking T-lymphocyte proliferation locally, suggesting a role of IDO in the regulation of immune responses. The goal of this study was to evaluate the potential of radiofluorinated carboximidamides as selective PET radioligands for IDO1. Specific binding correlated with IDO1 expression as measured through in vitro, microPET experiments...
January 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28117398/tryptophan-2-3-dioxygenase-tdo-deficiency-is-associated-with-subclinical-neuroprotection-in-a-mouse-model-of-multiple-sclerosis
#15
Tobias V Lanz, Sarah K Williams, Aleksandar Stojic, Simeon Iwantscheff, Jana K Sonner, Carl Grabitz, Simon Becker, Laura-Inés Böhler, Soumya R Mohapatra, Felix Sahm, Günter Küblbeck, Toshikazu Nakamura, Hiroshi Funakoshi, Christiane A Opitz, Wolfgang Wick, Ricarda Diem, Michael Platten
The catabolism of tryptophan to immunosuppressive and neuroactive kynurenines is a key metabolic pathway regulating immune responses and neurotoxicity. The rate-limiting step is controlled by indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO). IDO is expressed in antigen presenting cells during immune reactions, hepatic TDO regulates blood homeostasis of tryptophan and neuronal TDO influences neurogenesis. While the role of IDO has been described in multiple immunological settings, little is known about TDO's effects on the immune system...
January 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28077028/ferulic-acid-suppresses-expression-of-tryptophan-metabolic-key-enzyme-indoleamine-2-3-dioxygenase-via-nf%C3%AE%C2%BAb-and-p38-mapk-in-lipopolysaccharide-stimulated-microglial-cells
#16
Manami Koshiguchi, Hitoshi Komazaki, Shizuka Hirai, Yukari Egashira
Ferulic acid (FA) is a phenol compound found in plants that has anti-inflammatory properties. Indoleamine 2, 3-dioxygenase (IDO) is a tryptophan catabolic enzyme induced in immune cells, including glial cells, during inflammation. Enhanced IDO expression leads to reduced tryptophan levels and increased levels of toxic metabolites, including quinolinic acid. Therefore, inhibition of IDO expression may be effective in suppressing progression of neurodegenerative diseases. In this study, we examined the effect of FA in microglial cells on IDO expression levels and related inflammatory signal molecules...
May 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28041837/the-fate-of-technical-grade-chlordane-in-mice-fed-a-high-fat-diet-and-its-roles-as-a-candidate-obesogen
#17
Dezhen Wang, Xinru Wang, Ping Zhang, Yao Wang, Renke Zhang, Jin Yan, Zhiqiang Zhou, Wentao Zhu
Epidemiological studies indicate that exposure to persistent organic pollutants is positively associated with the prevalence of obesity. To delineate the potential role of technical-grade chlordane in obesity development, chlordane metabolism and chlordane-induced metabolic changes were investigated in mice fed high-fat diet (HFD) over a 6-week period. Gas chromatography-electron capture detector analysis showed that HFD induced more accumulation of technical chlordane in the liver, muscle and adipose tissue...
March 2017: Environmental Pollution
https://www.readbyqxmd.com/read/27914477/in-vitro-rescue-of-genital-strains-of-chlamydia-trachomatis-from-interferon-%C3%AE-and-tryptophan-depletion-with-indole-positive-but-not-indole-negative-prevotella-spp
#18
Noa Ziklo, Wilhelmina M Huston, Kuong Taing, Mohammad Katouli, Peter Timms
BACKGROUND: The natural course of sexually transmitted infections caused by Chlamydia trachomatis varies between individuals. In addition to parasite and host effects, the vaginal microbiota might play a key role in the outcome of C. trachomatis infections. Interferon-gamma (IFN-γ), known for its anti-chlamydial properties, activates the expression of indoleamine 2,3-dioxygenase (IDO1) in epithelial cells, an enzyme that catabolizes the amino acid L- tryptophan into N-formylkynurenine, depleting the host cell's pool of tryptophan...
December 3, 2016: BMC Microbiology
https://www.readbyqxmd.com/read/27891058/ido2-a-pathogenic-mediator-of-inflammatory-autoimmunity
#19
REVIEW
Lauren M F Merlo, Laura Mandik-Nayak
Indoleamine 2,3-dioxygenase 2 (IDO2), a homolog of the better-studied tryptophan-catabolizing enzyme IDO1, is an immunomodulatory molecule with potential effects on various diseases including cancer and autoimmunity. Here, we review what is known about the direct connections between IDO2 and immune function, particularly in relationship to autoimmune inflammatory disorders such as rheumatoid arthritis and lupus. Accumulating evidence indicates that IDO2 acts as a pro-inflammatory mediator of autoimmunity, with a functional phenotype distinct from IDO1...
2016: Clinical Medicine Insights. Pathology
https://www.readbyqxmd.com/read/27886064/probiotic-supplements-beneficially-affect-tryptophan-kynurenine-metabolism-and-reduce-the-incidence-of-upper-respiratory-tract-infections-in-trained-athletes-a-randomized-double-blinded-placebo-controlled-trial
#20
RANDOMIZED CONTROLLED TRIAL
Barbara Strasser, Daniela Geiger, Markus Schauer, Johanna M Gostner, Hannes Gatterer, Martin Burtscher, Dietmar Fuchs
BACKGROUND: Prolonged intense exercise has been associated with transient suppression of immune function and an increased risk of infections. In this context, the catabolism of amino acid tryptophan via kynurenine may play an important role. The present study examined the effect of a probiotic supplement on the incidence of upper respiratory tract infections (URTI) and the metabolism of aromatic amino acids after exhaustive aerobic exercise in trained athletes during three months of winter training...
November 23, 2016: Nutrients
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