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Tryptophan catabolism

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https://www.readbyqxmd.com/read/29190885/the-ido-inhibitor-1-methyl-tryptophan-activates-the-aryl-hydrocarbon-receptor-response-in-mesenchymal-stromal-cells
#1
Holly C Lewis, Raghavan Chinnadurai, Steven E Bosinger, Jacques Galipeau
The catabolism of tryptophan (Trp) by indoleamine 2,3-dioxygenase (IDO) is a key step in tolerance effected by a variety of cell types, including mesenchymal stromal cells (MSCs). Trp catabolism generates molecules known as kynurenines, whose tolerance mechanisms involve activation of the Aryl Hydrocarbon Receptor (AHR). A synthetic analog of Trp, 1-methyl tryptophan (1MT), is a selective inhibitor of IDO enzymatic activity being utilized in cancer immunotherapy trials. We hypothesized 1MT might activate AHR independently of its effects on IDO...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163470/indoleamine-2-3-dioxygenase-and-tolerance-where-are-we-now
#2
REVIEW
Andrew L Mellor, Henrique Lemos, Lei Huang
Cells expressing IDO suppress innate and adaptive immunity to promote tolerance by catabolizing the amino acid tryptophan (Trp) and other indole compounds. Interferon type I (IFN-I) and type II (IFN-II) produced at sites of inflammation or by activated immune cells are potent IDO inducers because mammalian IDO genes contain IFN response elements. Elevated IDO expression by dendritic cells (DCs) is of particular significance because IDO activity converts mature DCs into tolerogenic APCs that suppress effector T cells (Teff) and promote regulatory T cells (Tregs), thereby promoting tolerance...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29154462/the-role-of-indoleamine-2-3-dioxygenase-in-normal-and-pathological-pregnancies
#3
REVIEW
Rui-Qi Chang, Da-Jin Li, Ming-Qing Li
The survival of allogeneic fetus during pregnancy contradicts the laws of immune responses. Behind this paradoxical phenomenon, the mechanism is quite complex. Indoleamine-2,3-dioxygenase (IDO) is the first and rate-limiting enzyme of tryptophan catabolism. Emerging evidence shows that IDO is expressed at the maternal-fetal interface, including trophoblast cells, decidual stroma cells, decidual immune cells (eg, natural killer cells, T cells, and macrophages), and vascular endothelial cells of decidua and chorion...
November 20, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/29141444/associations-among-obesity-inflammation-and-tryptophan-catabolism-in-pregnancy
#4
Maureen Groer, Dietmar Fuchs, Allyson Duffy, Adetola Louis-Jacques, Amy D'Agata, Teodor T Postolache
OBJECTIVE: To evaluate relationships among obesity in pregnancy and plasma levels of tryptophan (TRP) and kynurenine (KYN), inflammatory markers, and depressed mood. METHODS: Pregnant women ( N = 374) were enrolled, and data were collected at a mean gestation of 20 weeks in this cross-sectional study. Plasma was analyzed for TRP, KYN, neopterin, and nitrite levels. Women completed demographic and mood scales. RESULTS: There was a statistically significant inverse correlation between body mass index (BMI) and TRP and positive correlations between BMI and KYN and the kynurenine/tryptophan (KYN/TRP) ratio...
January 1, 2017: Biological Research for Nursing
https://www.readbyqxmd.com/read/29118261/erratum-for-the-research-article-dysbiosis-of-the-gut-microbiota-is-associated-with-hiv-disease-progression-and-tryptophan-catabolism-by-i-vujkovic-cvijin-r-m-dunham-s-iwai-m-c-maher-r-g-albright-m-j-broadhurst-r-d-hernandez-m-m-lederman-y-huang-m-somsouk-s
#5
https://www.readbyqxmd.com/read/29113177/potential-role-of-indoleamine-2-3-dioxygenase-in-primary-biliary-cirrhosis
#6
Kashif Asghar, John Brain, Jeremy M Palmer, Stephen Douglass, Fatmah M A Naemi, Graeme O'Boyle, John Kirby, Simi Ali
Indoleamine 2,3-dioxygenase (IDO)-induced immunosuppression can be clinically beneficial for autoimmune diseases. Primary biliary cirrhosis (PBC) is characterized by autoimmune lesions of intrahepatic bile duct epithelial cells that may lead to irreversible cirrhosis or hepatocellular carcinoma. The present study assessed the expression and function of IDO in a cell culture model and in PBC patients. IDO expression was monitored in a human immortalized but non-malignant biliary epithelial cell (iBEC) line. Increased expression of IDO1/2 was observed in the iBECs following stimulation with interferon-γ (IFN-γ)...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29111717/discovery-of-a-novel-and-selective-indoleamine-2-3-dioxygenase-ido-1-inhibitor-3-5-fluoro-1h-indol-3-yl-pyrrolidine-2-5-dione-eos200271-pf-06840003-and-its-characterization-as-a-potential-clinical-candidate
#7
Stefano Crosignani, Patrick Bingham, Pauline Bottemanne, Hélène Cannelle, Sandra Cauwenberghs, Marie Cordonnier, Deepak Dalvie, Frederik Deroose, Jun Li Feng, Bruno Gomes, Samantha Greasley, Stephen E Kaiser, Manfred Kraus, Michel Négrerie, Karen A Maegley, Nichol Miller, Brion W Murray, Manfred Schneider, James Solowiej, Albert E Stewart, Joseph Tumang, Vince R Torti, Benoit Van den Eynde, Martin Wythes
Tumors use tryptophan-catabolizing enzymes such as Indoleamine 2,3-dioxygenase (IDO-1) to induce an immunosuppressive environment. IDO-1 is induced in response to inflammatory stimuli and promotes immune tolerance through effector T-cell anergy and enhanced Treg function. As such, IDO-1 is a nexus for the induction of key immunosuppressive mechanism and represents an important immunotherapeutic target in oncology. Starting from HTS hit 5, IDO-1 inhibitor 6 (EOS200271/PF-06840003) has been developed. SAR around 6 is described and rationalized using the X-ray crystal structure of 6 bound to human IDO-1, which shows that 6, differently from most of the IDO-1 inhibitors described so far, does not bind to the heme iron atom and has a novel binding mode...
November 7, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29099929/transcriptome-assessment-of-erythema-migrans-skin-lesions-in-patients-with-early-lyme-disease-reveals-predominant-interferon-signaling
#8
Adriana Marques, Ira Schwartz, Gary P Wormser, Yanmei Wang, Ronald L Hornung, Cumhur Y Demirkale, Peter J Munson, Siu-Ping Turk, Carla Williams, Chyi-Chia Richard Lee, Jun Yang, Mary M Petzke
Background: The most common clinical manifestation of early Lyme disease is the erythema migrans (EM) skin lesion that develops at the tick bite site typically between 7 and 14 days following infection with Borreliella burgdorferi. The host-pathogen interactions that occur in the skin may have a critical role in determining outcome of infection. Methods: Gene arrays were utilized to characterize the global transcriptional alterations in skin biopsy samples of EM lesions from untreated adult patients with Lyme disease in comparison to controls...
November 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29080891/prenatal-dynamics-of-kynurenine-pathway-metabolism-in-mice-focus-on-kynurenic-acid
#9
Nick Goeden, Francesca M Notarangelo, Ana Pocivavsek, Sarah Beggiato, Alexandre Bonnin, Robert Schwarcz
The kynurenine pathway (KP), the major catabolic route of tryptophan in mammals, contains several neuroactive metabolites, including kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK). KP metabolism, and especially the fate of KYNA, during pregnancy is poorly understood, yet it may play a significant role in the development of psychiatric disorders later in life. The present study was designed to investigate the prenatal features of KP metabolism in vivo, with special focus on KYNA. To this end, pregnant CD-1 mice were treated systemically with kynurenine (100 mg/kg), KYNA (10 mg/kg), or saline on embryonic day 18...
October 28, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/29080383/clinical-significance-of-tryptophan-catabolism-in-hodgkin-lymphoma
#10
Ayako Masaki, Takashi Ishida, Yasuhiro Maeda, Asahi Ito, Susumu Suzuki, Tomoko Narita, Shiori Kinoshita, Hisashi Takino, Takashi Yoshida, Masaki Ri, Shigeru Kusumoto, Hirokazu Komatsu, Hiroshi Inagaki, Ryuzo Ueda, Ilseung Choi, Youko Suehiro, Shinsuke Iida
Indoleamine 2,3-dioxygenase 1 (IDO) is an enzyme catabolizing tryptophan (Trp) into the kynurenine (Kyn) pathway. The purpose of the present study was to determine the clinical significance of Trp catabolism in newly-diagnosed Hodgkin Lymphoma (HL) patients. We quantified serum Trp and Kyn in 52 HL patients, and analyzed their associations with different clinical parameters including serum soluble CD30 (sCD30) concentration. IDO expression was evaluated in the patients' affected lymph nodes. The enrolled patients comprised 22 males and 30 females (age range 15-81, median 45 years), with a 5-year overall survival (OS) of 88...
October 28, 2017: Cancer Science
https://www.readbyqxmd.com/read/29051706/investigation-of-the-tissue-distribution-and-physiological-roles-of-indoleamine-2-3-dioxygenase-2
#11
Felicita F Jusof, Supun M Bakmiwewa, Silvia Weiser, Lay Khoon Too, Richard Metz, George C Prendergast, Stuart T Fraser, Nicholas H Hunt, Helen J Ball
Indoleamine 2,3-dioxygenase-2 (IDO2) is 1 of the 3 enzymes that can catalyze the first step in the kynurenine pathway of tryptophan metabolism. Of the 2 other enzymes, tryptophan 2,3-dioxygenase is highly expressed in the liver and has a role in tryptophan homeostasis, whereas indoleamine 2,3-dioxygenase-1 (IDO1) expression is induced by inflammatory stimuli. Indoleamine 2,3-dioxygenase-2 is reportedly expressed comparatively narrow, including in liver, kidney, brain, and in certain immune cell types, and it does not appear to contribute significantly to systemic tryptophan catabolism under normal physiological conditions...
2017: International Journal of Tryptophan Research: IJTR
https://www.readbyqxmd.com/read/28912017/indoleamine-2-3-dioxygenase-1-increased-in-human-gastric-pre-neoplasia-promotes-inflammation-and-metaplasia-in-mice-and-is-associated-with-type-ii-hypersensitivity-autoimmunity
#12
Mohamad El-Zaatari, Adam J Bass, Reanne Bowlby, Min Zhang, Li-Jyun Syu, Yitian Yang, Helmut Grasberger, Andrew Shreiner, Bei Tan, Shrinivas Bishu, Wai K Leung, Andrea Todisco, Nobuhiko Kamada, Marilia Cascalho, Andrzej A Dlugosz, John Y Kao
BACKGROUND & AIMS: Chronic gastrointestinal inflammation increases the risk of cancer by mechanisms that are not well understood. Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-binding enzyme that regulates the immune response via catabolization and regulation of tryptophan availability for immune cell uptake. IDO1 expression is increased during the transition from chronic inflammation to gastric metaplasia. We investigated whether IDO1 contributes to the inflammatory response that mediates loss of parietal cells leading to metaplasia...
September 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28886580/a-plasma-metabonomic-analysis-on-potential-biomarker-in-pyrexia-induced-by-three-methods-using-ultra-high-performance-liquid-chromatography-coupled-with-fourier-transform-ion-cyclotron-resonance-mass-spectrometry
#13
Ting Liu, Songhe Li, Xiumin Tian, Zhaoqin Li, Yue Cui, Fei Han, Yunli Zhao, Zhiguo Yu
Pyrexia usually is a systemic pathological process that can lead to metabolic disorders. Metabonomics as a powerful tool not only can reveal the pathological mechanisms, but also can give insight into the progression of pyrexia from another angle. Thus, an ultra high performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry (UHPLC-FT-ICR-MS) metabonomic approach was employed for the first time to investigate the plasma biochemical characteristics of pyrexia induced by three methods and to reveal subtle metabolic changes under the condition of pyrexia so as to explore its mechanism...
September 15, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28831293/3-hydroxykynurenine-and-3-hydroxyanthranilic-acid-enhance-the-toxicity-induced-by-copper-in-rat-astrocyte-culture
#14
Daniela Ramírez-Ortega, Alelí Ramiro-Salazar, Dinora González-Esquivel, Camilo Ríos, Benjamín Pineda, Verónica Pérez de la Cruz
Copper is an integral component of various enzymes, necessary for mitochondrial respiration and other biological functions. Excess copper is related with neurodegenerative diseases as Alzheimer and is able to modify cellular redox environment, influencing its functions, signaling, and catabolic pathways. Tryptophan degradation through kynurenine pathway produces some metabolites with redox properties as 3-hydroxykynurenine (3-HK) and 3-hydroxyanthranilic acid (3-HANA). The imbalance in their production is related with some neuropathologies, where the common factors are oxidative stress, inflammation, and cell death...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28792588/immunosuppressive-enzymes-in-the-tumor-microenvironment
#15
REVIEW
Valérie Molinier-Frenkel, Flavia Castellano
Antigen encounter by T lymphocytes induces important metabolic changes. Antitumor T lymphocytes enter in a metabolic competition with tumors, which divert feedback mechanisms of the immune response. Immunosuppressive enzymes, modifying the nutrient availability and leading to the production of toxic catabolites, represent one of these mechanisms, contributing to the metabolic halo in which T lymphocytes evolve during immune responses. Two classes of immunosuppressive enzymes, expressed by the tumor cells or by cells of the microenvironment, have been described: those catabolizing essential or semiessential amino acids, tryptophan, arginine, and phenylalanine and the ectoenzymes, which degrade the ATP to produce adenosine...
October 2017: FEBS Letters
https://www.readbyqxmd.com/read/28758106/neopterin-as-a-biomarker-of-immune-response-in-cancer-patients
#16
REVIEW
Bohuslav Melichar, Martina Spisarová, Marie Bartoušková, Lenka Kujovská Krčmová, Lenka Javorská, Hana Študentová
With the advent of immunotherapy the topic of biomarkers of immune response is of high interest. Along with the expression of programmed death ligand 1 (PD-L1) or tumor infiltrating lymphocytes (TIL), biomarkers of macrophage activation could be of interest. Neopterin is a biomarker of immune activation increased in different disorders associated with immune activation, including cancer. Neopterin synthesis is induced by interferon-γ that also induces indoleamine 2,3-dioxygenase (IDO), an enzyme catalyzing catabolism of tryptophan to kynurenine...
July 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28751584/kynurenines-tryptophan-s-metabolites-in-exercise-inflammation-and-mental-health
#17
REVIEW
Igor Cervenka, Leandro Z Agudelo, Jorge L Ruas
Kynurenine metabolites are generated by tryptophan catabolism and regulate biological processes that include host-microbiome signaling, immune cell response, and neuronal excitability. Enzymes of the kynurenine pathway are expressed in different tissues and cell types throughout the body and are regulated by cues, including nutritional and inflammatory signals. As a consequence of this systemic metabolic integration, peripheral inflammation can contribute to accumulation of kynurenine in the brain, which has been associated with depression and schizophrenia...
July 28, 2017: Science
https://www.readbyqxmd.com/read/28727234/kynurenine-a-tryptophan-metabolite-that-accumulates-with-age-induces-bone-loss
#18
Mona El Refaey, Meghan E McGee-Lawrence, Sadanand Fulzele, Eileen J Kennedy, Wendy B Bollag, Mohammed Elsalanty, Qing Zhong, Ke-Hong Ding, Nathaniel G Bendzunas, Xing-Ming Shi, Jianrui Xu, William D Hill, Maribeth H Johnson, Monte Hunter, Jessica L Pierce, Kanglun Yu, Mark W Hamrick, Carlos M Isales
Age-dependent bone loss occurs in humans and in several animal species, including rodents. The underlying causal mechanisms are probably multifactorial, although an age-associated increase in the generation of reactive oxygen species has been frequently implicated. We previously reported that aromatic amino acids function as antioxidants, are anabolic for bone, and that they may potentially play a protective role in an aging environment. We hypothesized that upon oxidation the aromatic amino acids would not only lose their anabolic effects but also potentially become a catabolic byproduct...
November 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28659716/aspects-of-tryptophan-and-nicotinamide-adenine-dinucleotide-in-immunity-a-new-twist-in-an-old-tale
#19
REVIEW
Hector Rodriguez Cetina Biefer, Anju Vasudevan, Abdallah Elkhal
Increasing evidence underscores the interesting ability of tryptophan to regulate immune responses. However, the exact mechanisms of tryptophan's immune regulation remain to be determined. Tryptophan catabolism via the kynurenine pathway is known to play an important role in tryptophan's involvement in immune responses. Interestingly, quinolinic acid, which is a neurotoxic catabolite of the kynurenine pathway, is the major pathway for the de novo synthesis of nicotinamide adenine dinucleotide (NAD+). Recent studies have shown that NAD+, a natural coenzyme found in all living cells, regulates immune responses and creates homeostasis via a novel signaling pathway...
2017: International Journal of Tryptophan Research: IJTR
https://www.readbyqxmd.com/read/28651456/phytochemical-treatments-target-kynurenine-pathway-induced-oxidative-stress
#20
K Parasram
OBJECTIVE: The objective of this paper was to link the phytochemical and metabolic research treating quinolinic acid induced oxidative stress in neurodegenerative disorders. METHODS: Quinolinic acid, a metabolite of the kynurenine pathway of tryptophan catabolism, plays a role in the oxidative stress associated with many neurological disorders and is used to simulate disorders such as Parkinson's disease. RESULTS: In these models, phytochemicals have been shown to reduce striatal lesion size, reduce inflammation and prevent lipid peroxidation caused by quinolinic acid...
June 26, 2017: Redox Report: Communications in Free Radical Research
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