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"kynurenine pathway"

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https://www.readbyqxmd.com/read/28631232/activation-of-brain-indoleamine-2-3-dioxygenase-contributes-to-depressive-like-behavior-induced-by-an-intracerebroventricular-injection-of-streptozotocin-in-mice
#1
Leandro Cattelan Souza, Cristiano R Jesse, Marcelo Gomes de Gomes, Lucian Del Fabbro, André Tiago Rossito Goes, Franciele Donato, Silvana Peterini Boeira
There is a lack of information concerning the molecular events underlying the depressive-like effect of an intracerebroventricular injection of streptozotocin (ICV-STZ) in mice. The elevated activity of the tryptophan-degrading enzyme indoleamine-2,3-dioxygenase (IDO) has been proposed to mediate depression in inflammatory disorders. In the present study, we reported that ICV-STZ activates IDO in the hippocampus of mice and culminates in depressive-like behaviors, as measured by the increased duration of immobility in the tail suspension test and decreased sucrose intake in the sucrose preference test...
June 19, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28628213/changes-in-kynurenine-pathway-metabolism-in-parkinson-patients-with-l-dopa-induced-dyskinesia
#2
Jesper F Havelund, Andreas D Andersen, Michael Binzer, Morten Blaabjerg, Niels H H Heegaard, Egon Stenager, Nils J Faergeman, Jan Bert Gramsbergen
L-DOPA is the most effective drug in the symptomatic treatment of Parkinson's disease, but chronic use is associated with L-DOPA-induced dyskinesia in more than half the patients after 10 years of treatment. L-DOPA treatment may affect tryptophan metabolism via the kynurenine pathway. Altered levels of kynurenine metabolites can affect glutamatergic transmission and may play a role in the development of L-DOPA-induced dyskinesia. In this study we assessed kynurenine metabolites in plasma and cerebrospinal fluid of Parkinson's disease patients and controls...
June 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28602601/association-of-amine-biomarkers-with-incident-dementia-and-alzheimer-s-disease-in-the-framingham-study
#3
Vincent Chouraki, Sarah R Preis, Qiong Yang, Alexa Beiser, Shuo Li, Martin G Larson, Galit Weinstein, Thomas J Wang, Robert E Gerszten, Ramachandran S Vasan, Sudha Seshadri
INTRODUCTION: The identification of novel biomarkers associated with Alzheimer's disease (AD) could provide key biological insights and permit targeted preclinical prevention. We investigated circulating metabolites associated with incident dementia and AD using metabolomics. METHODS: Plasma levels of 217 metabolites were assessed in 2067 dementia-free Framingham Offspring Cohort participants (mean age = 55.9 ± 9.7 years; 52.4% women). We studied their associations with future dementia and AD risk in multivariate Cox models...
June 8, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28590049/chromatographic-analysis-of-tryptophan-metabolites
#4
REVIEW
Ilona Sadok, Andrzej Gamian, Magdalena Maria Staniszewska
The kynurenine pathway generates multiple tryptophan metabolites called collectively kynurenines and leads to formation of the enzyme co-factor NAD. The first step in this pathway is tryptophan degradation, initiated by the rate-limiting enzymes indoleamine 2,3-dioxygenase or tryptophan 2,3-dioxygenase, depending on the tissue. The balanced kynurenine metabolism, which has been a subject of multiple studies in last decades, plays an important role in several physiological and pathological conditions such as infections, autoimmunity, neurological disorders, cancer, cataracts, as well as pregnancy...
June 7, 2017: Journal of Separation Science
https://www.readbyqxmd.com/read/28559281/uridine-monophosphate-synthetase-enables-eukaryotic-de-novo-nad-biosynthesis-from-quinolinic-acid
#5
Melanie R McReynolds, Wenqing Wang, Lauren M Holleran, Wendy Hanna-Rose
NAD+ biosynthesis is an attractive and promising therapeutic target for influencing healthspan and obesity-related phenotypes as well as tumor growth. Full and effective use of this target for therapeutic benefit requires a complete understanding of NAD+ biosynthetic pathways. Here we report a previously unrecognized role for a conserved phosphoribosyltransferase in NAD+ biosynthesis. Because a required quinolinic acid phosphoribosyltransferase (QPRTase) is not encoded in its genome, Caenorhabditis elegans are reported to lack a de novo NAD+ biosynthetic pathway...
May 30, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28557618/microenvironment-tumor-metabolic-interactions-highlighted-by-qmsi-application-to-the-tryptophan-kynurenine-pathway-in-immuno-oncology
#6
Rima Ait-Belkacem, Vanesa Bol, Gregory Hamm, Florence Schramme, Benoit Van Den Eynde, Lauranne Poncelet, Fabien Pamelard, Jonathan Stauber, Bruno Gomes
Inhibition of NK and effector T-cell functions and activation of regulatory cell populations are the main immunosuppressive effects of indoleamine-2,3-dioxygenase1 (IDO1). By converting tryptophan (Trp) into kynurenine (Kyn), IDO1 is involved in the immune response homeostasis, and its dysregulated expression is described in immune-related pathologies, as tumors that hijack it to evade immune destruction. Thereby, IDO1 inhibitors are being developed to stimulate antitumor immune responses. Existing and standard quantitation methods of IDO1 substrate and metabolite(s) are based on the total level of Trp and its metabolites determined by liquid chromatography tandem mass spectrometry analysis in human plasma, cerebrospinal fluid, and brain...
May 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28551532/effects-of-tryptophan-kynurenine-and-kynurenic-acid-exerted-on-human-reconstructed-corneal-epithelium-in-vitro
#7
Anna Matysik-Woźniak, Roman Paduch, Waldemar A Turski, Ryszard Maciejewski, Anselm G Jünemann, Robert Rejdak
BACKGROUND: Tryptophan metabolites formed along kynurenine pathway may affect cell proliferation and tissue function. This pathway presents potential sites for drug discovery. Tryptophan and its metabolites kynurenine and kynurenic acid may be involved in the physiology and pathology of the ocular surface. The purpose of this work is to investigate the effect exerted by tryptophan, kynurenine and kynurenic acid upon corneal epithelium. METHODS: A SkinEthic™ HCE human reconstructed corneal epithelium model was used...
February 24, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28546077/systemic-administration-of-l-kynurenine-sulfate-induces-cerebral-hypoperfusion-transients-in-adult-c57bl-6-mice
#8
Dániel Péter Varga, Ákos Menyhárt, Tamás Puskás, Ferenc Bari, Eszter Farkas, Zsolt Kis, László Vécsei, József Toldi, Levente Gellért
The kynurenine pathway is a cascade of enzymatic steps generating biologically active compounds. l-kynurenine (l-KYN) is a central metabolite of tryptophan degradation. In the mammalian brain, l-KYN is partly converted to kynurenic acid (KYNA), which exerts multiple effects on neurotransmission. Recently, l-KYN or one of its derivatives were attributed a direct role in the regulation of the systemic circulation. l-KYN dilates arterial blood vessels during sepsis in rats, while it increases cerebral blood flow (CBF) in awake rabbits...
May 22, 2017: Microvascular Research
https://www.readbyqxmd.com/read/28539670/simvastatin-and-bezafibrate-ameliorate-emotional-disorder-induced-by-high-fat-diet-in-c57bl-6-mice
#9
Hui Wang, Jia Zhou, Qiong Zhen Liu, Lu Lu Wang, Jing Shang
High fat diet (HFD)-induced metabolic disorders may lead to emotional disorders. This study aimed to explore the effect of simvastatin (SMV) and bezafibrate (BZ) on improving HFD-induced emotional changes, and tried to identify their different mechanisms. The intraperitoneal glucose tolerance test (IPGTT) was used to evaluate glucose control ability; and behavior tests including open field tests (OFT), forced swimming tests (FST), tail suspension tests (TST) and sucrose preference (SPT), were then performed to evaluate emotional changes...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28529072/rescue-of-il-1%C3%AE-induced-reduction-of-human-neurogenesis-by-omega-3-fatty-acids-and-antidepressants
#10
Alessandra Borsini, Silvia Alboni, Mark A Horowitz, Luis M Tojo, Giuseppe Cannazza, Kuan-Pin Su, Carmine M Pariante, Patricia A Zunszain
Both increased inflammation and reduced neurogenesis have been associated with the pathophysiology of major depression. We have previously described how interleukin-1 (IL-1) β, a pro-inflammatory cytokine increased in depressed patients, decreases neurogenesis in human hippocampal progenitor cells. Here, using the same human in vitro model, we show how omega-3 (ω-3) polyunsaturated fatty acids and conventional antidepressants reverse this reduction in neurogenesis, while differentially affecting the kynurenine pathway...
May 18, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28527020/changes-in-serum-levels-of-kynurenine-metabolites-in-paediatric-patients-affected-by-adhd
#11
Melania Evangelisti, Pietro De Rossi, Jole Rabasco, Renato Donfrancesco, Luana Lionetto, Matilde Capi, Gabriele Sani, Maurizio Simmaco, Ferdinando Nicoletti, Maria Pia Villa
This study aims at determining serum levels of tryptophan and other metabolites of the kynurenine pathway in children with attention deficit hyperactivity disorder (ADHD) compared to healthy controls. Such metabolites interact with glutamate receptors in the central nervous system, potentially modulating mechanisms that are pivotal in ADHD and thus potentially representing peripheral biomarkers of the disorder. We measured serum levels of tryptophan and some metabolites of the kynurenine pathway in 102 children with ADHD and 62 healthy controls by liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
May 19, 2017: European Child & Adolescent Psychiatry
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
#12
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/28511073/preparation-and-evaluation-of-l-and-d-5-18-f-fluorotryptophan-as-pet-imaging-probes-for-indoleamine-and-tryptophan-2-3-dioxygenases
#13
Tang Tang, Herman S Gill, Annie Ogasawara, Jeff N Tinianow, Alexander N Vanderbilt, Simon-Peter Williams, Georgia Hatzivassiliou, Sharla White, Wendy Sandoval, Kevin DeMent, Mengling Wong, Jan Marik
Indoleamine and tryptophan 2,3-dioxygenases (IDO1 and TDO2) are pyrrolases catalyzing the oxidative cleavage of the 2,3-double bond of L-tryptophan in kynurenine pathway. In the tumor microenvironment, their increased activity prevents normal immune function, i.e. tumor cell recognition and elimination by cytotoxic T-cells. Consequently, inhibition of the kynurenine pathway may enhance the activity of cancer immunotherapeutics by reversing immune dysfunction. We sought to investigate the properties of radiolabeled 5-[(18)F]fluorotryptophan with respect to its ability for measuring IDO1 and TDO2 activity by positron emission tomography (PET)...
May 5, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28507519/vasorelaxing-action-of-the-kynurenine-metabolite-xanthurenic-acid-the-missing-link-in-endotoxin-induced-hypotension
#14
Francesco Fazio, Albino Carrizzo, Luana Lionetto, Antonio Damato, Luca Capocci, Mariateresa Ambrosio, Giuseppe Battaglia, Valeria Bruno, Michele Madonna, Maurizio Simmaco, Ferdinando Nicoletti, Carmine Vecchione
The kynurenine pathway of tryptophan metabolism is activated by pro-inflammatory cytokines. L-kynurenine, an upstream metabolite of the pathway, acts as a putative endothelium-derived relaxing factor, and has been hypothesized to play a causative role in the pathophysiology of inflammation-induced hypotension. Here, we show that xanthurenic acid (XA), the transamination product of 3-hydroxykynurenine, is more efficacious than L-kynurenine in causing relaxation of a resistance artery, but fails to relax pre-contracted aortic rings...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28506496/twins-labeling-liquid-chromatography-mass-spectrometry-based-metabolomics-for-absolute-quantification-of-tryptophan-and-its-key-metabolites
#15
Huimin Guo, Yu Jiao, Xu Wang, Tao Lu, Zunjian Zhang, Fengguo Xu
Tryptophan metabolism plays a crucial role in mediating gastrointestinal function. Here, in order to absolutely quantify tryptophan and its metabolites, a liquid chromatography-mass spectrometry (LC-MS) based targeted metabolomics approach was developed using N-dimethyl-/N-diethyl-amino naphthalene-1-sulfonyl chloride (Dns/Dens-Cl) as twins labeling (TL) reagents. Dns-Cl is famous in amine and phenol derivations, and structure is similar with Dens-Cl. The introduction of easily protonated moiety of tertiary ammonium-containing part in the derivatives from Dns to tryptophan and its metabolites not only improved the LC separation but also enhanced their MS response...
May 5, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28496435/serum-metabolomic-profiling-of-piglets-infected-with-virulent-classical-swine-fever-virus
#16
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/28490533/the-tryptophan-kynurenine-pathway-systemic-inflammation-and-long-term-outcome-after-kidney-transplantation
#17
Laura V de Vries, Isidor Minovic, Casper Fm Franssen, Martijn van Faassen, Jan-Stephan F Sanders, Stefan P Berger, Gerjan Navis, Ido P Kema, Stephan Jl Bakker
BACKGROUND: Tryptophan is metabolized along the kynurenine pathway, initially to kynurenine, and subsequently to cytotoxic 3-hydroxykynurenine. There is increasing interest in this pathway, because of its pro-inflammatory nature, and drugs interfering in it receive increasing attention. We aimed to investigate whether serum and urinary parameters of the tryptophan-kynurenine pathway, and particularly cytotoxic 3-hydroxykynurenine, are associated with systemic inflammation and long-term outcome in renal transplant recipients (RTR)...
May 10, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28490020/maternal-inflammation-results-in-altered-tryptophan-metabolism-in-rabbit-placenta-and-fetal-brain
#18
Monica Williams, Zhi Zhang, Elizabeth Nance, Julia L Drewes, Wojciech G Lesniak, Sarabdeep Singh, Diane C Chugani, Kannan Rangaramanujam, David R Graham, Sujatha Kannan
Maternal inflammation has been linked to neurodevelopmental and neuropsychiatric disorders such as cerebral palsy, schizophrenia, and autism. We had previously shown that intrauterine inflammation resulted in a decrease in serotonin, one of the tryptophan metabolites, and a decrease in serotonin fibers in the sensory cortex of newborns in a rabbit model of cerebral palsy. In this study, we hypothesized that maternal inflammation results in alterations in tryptophan pathway enzymes and metabolites in the placenta and fetal brain...
May 11, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28482311/tryptophan-breakdown-and-cognition-in-bipolar-disorder
#19
Martina Platzer, Nina Dalkner, Frederike T Fellendorf, Armin Birner, Susanne A Bengesser, Robert Queissner, Nora Kainzbauer, René Pilz, Simone Herzog-Eberhard, Carlo Hamm, Christa Hörmanseder, Alexander Maget, Philipp Rauch, Harald Mangge, Dietmar Fuchs, Sieglinde Zelzer, Gregor Schütze, Natalie Moll, Markus J Schwarz, Rodrigo B Mansur, Roger S McIntyre, Eva Z Reininghaus
INTRODUCTION: It has been demonstrated that bipolar disorder (BD) is often accompanied by cognitive deficits across all subdomains including verbal memory, attention and executive functioning. Cognitive deficits are observed both during episodes of mania or depression, as well as during the euthymic phase. It has been proposed that chronic immune-mediated inflammation in the central nervous system results in alterations in neural structures that subserve cognitive function. Kynurenine is an intermediate in the inflammatory cascade and can be peripherally measured to proxy inflammatory activity...
April 27, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28469468/kynurenine-pathway-of-tryptophan-metabolism-regulatory-and-functional-aspects
#20
REVIEW
Abdulla A-B Badawy
Regulatory and functional aspects of the kynurenine (K) pathway (KP) of tryptophan (Trp) degradation are reviewed. The KP accounts for ~95% of dietary Trp degradation, of which 90% is attributed to the hepatic KP. During immune activation, the minor extrahepatic KP plays a more active role. The KP is rate-limited by its first enzyme, Trp 2,3-dioxygenase (TDO), in liver and indoleamine 2,3-dioxygenase (IDO) elsewhere. TDO is regulated by glucocorticoid induction, substrate activation and stabilization by Trp, cofactor activation by heme, and end-product inhibition by reduced nicotinamide adenine dinucleotide (phosphate)...
2017: International Journal of Tryptophan Research: IJTR
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