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Tryptophan catabolism

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https://www.readbyqxmd.com/read/28792588/immunosuppressive-enzymes-in-the-tumor-microenvironement
#1
REVIEW
Valérie Molinier-Frenkel, Flavia Castellano
Antigen encounter by T lymphocytes induces important metabolic changes. Anti-tumor 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 semi-essential amino acids, tryptophan, arginine and phenylalanine and the ectoenzymes, which degrade the ATP to produce adenosine...
August 9, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28758106/neopterin-as-a-biomarker-of-immune-response-in-cancer-patients
#2
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
#3
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
#4
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 and 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...
July 20, 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
#5
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
#6
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
https://www.readbyqxmd.com/read/28650043/heme-containing-enzymes-and-inhibitors-for-tryptophan-metabolism
#7
REVIEW
Daojing Yan, Ying-Wu Lin, Xiangshi Tan
Iron-containing enzymes such as heme enzymes play crucial roles in biological systems. Three distinct heme-containing dioxygenase enzymes, tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase 1 (IDO1) and indoleamine 2,3-dioxygenase 2 (IDO2) catalyze the initial and rate-limiting step of l-tryptophan catabolism through the kynurenine pathway in mammals. Overexpression of these enzymes causes depletion of tryptophan and the accumulation of metabolic products, which contributes to tumor immune tolerance and immune dysregulation in a variety of disease pathologies...
June 26, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28637803/protein-malnutrition-alters-tryptophan-and-angiotensin-converting-enzyme-2-homeostasis-and-adaptive-immune-responses-in-human-rotavirus-infected-gnotobiotic-pigs-transplanted-with-human-infant-fecal-microbiota
#8
David D Fischer, Sukumar Kandasamy, Francine C Paim, Stephanie N Langel, Moyasar A Alhamo, Lulu Shao, Juliet Chepngeno, Ayako Miyazaki, Huang-Chi Huang, Anand Kumar, Gireesh Rajashekara, Linda J Saif, Anastasia N Vlasova
Malnutrition leads to increased morbidity and is evident in almost half of all deaths in children under the age of five. Mortality due to rotavirus diarrhea is common in developing countries where malnutrition is prevalent; however, the relationship between malnutrition and rotavirus infection remains unclear. In this study, gnotobiotic pigs transplanted with the fecal microbiota of a healthy 2-month-old infant were fed protein-sufficient or -deficient diets with infected with virulent human rotavirus. After human rotavirus infection, protein deficient pigs had decreased human rotavirus antibody titers and total IgA concentrations, systemic T helper (CD3+CD4+) and cytotoxic T (CD3+CD8+) lymphocyte frequencies and serum tryptophan and angiotensin I converting enzyme 2...
June 21, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28625979/intestine-specific-homeobox-gene-isx-integrates-il6-signaling-tryptophan-catabolism-and-immune-suppression
#9
Li-Ting Wang, Shyh-Shin Chiou, Chee-Yin Chai, Edward Hsi, Kazunari K Yokoyama, Shen-Nien Wang, Shau-Ku Huang, Shih-Hsien Hsu
The intestine-specific homeobox transcription factor intestine-specific homeobox (ISX) is an IL6-inducible proto-oncogene implicated in the development of hepatocellular carcinoma, but its mechanistic contributions to this process are undefined. In this study, we provide evidence that ISX mediates a positive feedback loop integrating inflammation, tryptophan catabolism, and immune suppression. We found that ISX-mediated IL6-induced expression of the tryptophan catabolic enzymes Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase in hepatocellular carcinoma cells, resulting in an ISX-dependent increase in the tryptophan catabolite kynurenine and its receptor aryl hydrocarbon receptor (AHR)...
June 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28595944/ido-chronic-immune-activation-and-tryptophan-metabolic-pathway-a-potential-pathophysiological-link-between-depression-and-obesity
#10
REVIEW
Adriano José Maia Chaves Filho, Camila Nayane Carvalho Lima, Silvânia Maria Mendes Vasconcelos, David Freitas de Lucena, Michael Maes, Danielle Macedo
Obesity and depression are among the most pressing health problems in the contemporary world. Obesity and depression share a bidirectional relationship, whereby each condition increases the risk of the other. By inference, shared pathways may underpin the comorbidity between obesity and depression. Activation of cell-mediated immunity (CMI) is a key factor in the pathophysiology of depression. CMI cytokines, including IFN-γ, TNFα and IL-1β, induce the catabolism of tryptophan (TRY) by stimulating indoleamine 2,3-dioxygenase (IDO) resulting in the synthesis of kynurenine (KYN) and other tryptophan catabolites (TRYCATs)...
June 12, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28585214/the-interactions-between-kynurenine-folate-methionine-and-pteridine-pathways-in-obesity
#11
Ayse Basak Engin, Atilla Engin
Obesity activates both innate and adaptive immune responses in adipose tissue. Elevated levels of eosinophils with depression of monocyte and neutrophil indicate the deficiencies in the immune system of morbidly obese individuals. Actually, adipose tissue macrophages are functional antigen-presenting cells that promote the proliferation of interferon-gamma (IFN-gamma)-producing CD4+ T cells in adipose tissue of obese subjects. Eventually, diet-induced obesity is associated with the loss of tissue homeostasis and development of type 1 inflammatory responses in visceral adipose tissue...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28581352/interferon-%C3%AE-mediates-the-immunosuppression-of-bone-marrow-mesenchymal-stem-cells-on-t-lymphocytes-in-vitro
#12
Chen Liang, Erlie Jiang, Jianfeng Yao, Mei Wang, Shulian Chen, Zheng Zhou, Weihua Zhai, Qiaoling Ma, Sizhou Feng, Mingzhe Han
OBJECTIVES: In the present study, we first confirmed the suppressive function of MSCs in allogeneic T cell proliferation and then examined the underlying mechanisms for MSCs' immunomodulation and the role of the pro-inflammatory cytokine interferon (IFN)-γ. METHODS: Human MSCs were cultured in the presence or absence of IFN-γ. The expression level of prostaglandin E2 (PGE2), hepatocyte growth factor (HGF), transforming growth factor (TGF)-β1 and indoleamine 2,3-dioxygenase (IDO) by MSCs were measured...
June 5, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28560878/serial-metabolome-changes-in-a-prospective-cohort-of-subjects-with-influenza-viral-infection-and-comparison-with-dengue-fever
#13
Liang Cui, Jinling Fang, Eng Eong Ooi, Yie Hou Lee
Influenza virus infection (IVI) and dengue virus infection (DVI) are major public health threats. Between IVI and DVI, clinical symptoms can be overlapping yet infection-specific, but host metabolome changes are not well-described. Untargeted metabolomics and targeted oxylipinomic analyses were performed on sera serially collected at three phases of infection from a prospective cohort study of adult subjects with either H3N2 influenza infection or dengue fever. Untargeted metabolomics identified 26 differential metabolites, and major perturbed pathways included purine metabolism, fatty acid biosynthesis and β-oxidation, tryptophan metabolism, phospholipid catabolism, and steroid hormone pathway...
June 12, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28549143/bile-acids-and-tryptophan-metabolism-are-novel-pathways-involved-in-metabolic-abnormalities-in-bpa-exposed-pregnant-mice-and-male-offspring
#14
Martha Susiarjo, Frances Xin, Martha Stefaniak, Clementina Mesaros, Rebecca A Simmons, Marisa S Bartolomei
Increasing evidence has demonstrated that exposure to endocrine disrupting chemicals (EDCs) impacts maternal and fetal health, but the underlying mechanisms are still unclear. We have previously shown that dietary exposure to 10 µg/kg bw/day and 10 mg/kg bw/day bisphenol A (BPA) during pregnancy induced metabolic abnormalities in F1 male offspring and gestational glucose intolerance in F0 pregnant mice. The aim of this study is to elucidate the underlying etiologies of BPA exposure-induced metabolic disease by analyzing male fetal liver metabolome...
May 25, 2017: Endocrinology
https://www.readbyqxmd.com/read/28526475/identification-and-preliminary-structure-activity-relationships-of-1-indanone-derivatives-as-novel-indoleamine-2-3-dioxygenase-1-ido1-inhibitors
#15
Dingding Gao, Yingxia Li
Indoleamine 2,3-dioxygenase 1 (IDO1) plays a vital role in the catabolism of tryptophan along with the kynurenine pathway which is involved in many human diseases including cancer, Alzheimer's disease, etc. In this study, compound 1 bearing a 1-Indanone scaffold was identified as a novel IDO1 inhibitor by structure-based virtual screening, with moderate to good enzymatic and cellular inhibitory activities. Also, surface plasmon resonance analysis validated the direct interaction between compound 1 and IDO1 protein...
May 10, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28511640/tryptophan-catabolism-and-immune-activation-in-primary-and-chronic-hiv-infection
#16
Marco Gelpi, Hans J Hartling, Per M Ueland, Henrik Ullum, Marius Trøseid, Susanne D Nielsen
BACKGROUND: Kynurenine/Tryptophan ratio (KTR) is increased in HIV infection, and linked to immune activation. We hypothesized that early cART initiation results in lower KTR compared to late initiation. Furthermore, we hypothesized that KTR prior to cART is a predictor of the magnitude of subsequent reduction in immune activation. METHODS: Prospective study including 57 HIV-infected individuals (primary HIV infection (N = 14), early presenters (>350 CD4+ T cells/μL, N = 24), late presenters (<200 CD4+ T cells/μL, N = 19))...
May 16, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28496435/serum-metabolomic-profiling-of-piglets-infected-with-virulent-classical-swine-fever-virus
#17
Wenjie Gong, Junjie Jia, Bikai Zhang, Shijiang Mi, Li Zhang, Xiaoming Xie, Huancheng Guo, Jishu Shi, Changchun Tu
Classical swine fever (CSF) is a highly contagious swine infectious disease and causes significant economic losses for the pig industry worldwide. The objective of this study was to determine whether small molecule metabolites contribute to the pathogenesis of CSF. Birefly, serum metabolomics of CSFV Shimen strain-infected piglets were analyzed by ultraperformance liquid chromatography/electrospray ionization time-of-flight mass spectrometry (UPLC/ESI-Q-TOF/MS) in combination with multivariate statistical analysis...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28468882/serum-metabolomics-investigation-of-humanized-mouse-model-of-dengue-virus-infection
#18
Liang Cui, Jue Hou, Jinling Fang, Yie Hou Lee, Vivian Vasconcelos Costa, Lan Hiong Wong, Qingfeng Chen, Eng Eong Ooi, Steven R Tannenbaum, Jianzhu Chen, Choon Nam Ong
Dengue is an acute febrile illness caused by dengue virus (DENV) and a major cause of morbidity and mortality in tropical and subtropical regions of the world. The lack of an appropriate small-animal model of dengue infection has greatly hindered the study of dengue pathogenesis and the development of therapeutics. In this study, we conducted mass spectrometry-based serum metabolic profiling from a model using humanized mice (humice) with DENV serotype 2 infection at 0, 3, 7, 14, and 28 days postinfection (dpi)...
July 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28456683/patchouli-alcohol-ameliorates-dextran-sodium-sulfate-induced-experimental-colitis-and-suppresses-tryptophan-catabolism
#19
Chang Qu, Zhong-Wen Yuan, Xiu-Ting Yu, Yan-Feng Huang, Guang-Hua Yang, Jian-Nan Chen, Xiao-Ping Lai, Zi-Ren Su, Hui-Fang Zeng, Ying Xie, Xiao-Jun Zhang
Despite the increased morbidity of ulcerative colitis (UC) in recent years, available treatments remain unsatisfactory. Pogostemon cablin has been widely applied to treat a variety of gastrointestinal disorders in clinic for centuries, in which patchouli alcohol (PA, C15H26O) has been identified as the major active component. This study attempted to determine the bioactivity of PA on dextran sulfate sodium (DSS)-induced mice colitis and clarify the mechanism of action. Acute colitis was induced in mice by 3% DSS for 7 days...
April 27, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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
#20
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...
July 2017: Immunological Investigations
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