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Kynurenin

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https://www.readbyqxmd.com/read/28527020/changes-in-serum-levels-of-kynurenine-metabolites-in-paediatric-patients-affected-by-adhd
#1
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
#2
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/28524767/immune-biomarkers-in-older-adults-role-of-physical-activity
#3
Vanessa Valdiglesias, María Sánchez-Flores, Ana Maseda, Laura Lorenzo-López, Diego Marcos-Pérez, Ana López-Cortón, Barbara Strasser, Dietmar Fuchs, Blanca Laffon, José C Millán-Calenti, Eduardo Pásaro
Aging is associated with a decline in the normal functioning of the immune system. Several studies described the relationship between immunological alterations, including immunosenescence and inflammation, and aging or age-related outcomes, such as sarcopenia, depression, and neurodegenerative disorders. Physical activity is known to improve muscle function and to exert a number of benefits on older adult health, including reduced risk for heart and metabolic system chronic diseases. However, the positive influence of physical activity on the immune system has not been elucidated...
May 19, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28511640/tryptophan-catabolism-and-immune-activation-in-primary-and-chronic-hiv-infection
#4
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/28511073/preparation-and-evaluation-of-l-and-d-5-18-f-fluorotryptophan-as-pet-imaging-probes-for-indoleamine-and-tryptophan-2-3-dioxygenases
#5
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
#6
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
#7
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/28502732/swimming-exercise-prevents-behavioural-disturbances-induced-by-an-intracerebroventricular-injection-of-amyloid-%C3%AE-1-42-peptide-through-modulation-of-cytokine-nf-kappab-pathway-and-indoleamine-2-3-dioxygenase-in-mouse-brain
#8
Leandro Cattelan Souza, Cristiano R Jesse, Lucian Del Fabbro, Marcelo de Gomes, André Tiago Rossito Goes, Carlos Borges Filho, Cristiane Luchese, Albanin Aparecida Mielniczki Pereira, Silvana Peterini Boeira
Emerging evidence indicates that the activation of indoleamine-2,3-dioxygenase (IDO), a first and rate-limiting enzyme in the kynurenine (KYN) pathway, is involved in amyloid-beta (Aβ1-42)-neurotoxicity and Alzheimer's disease (AD) pathogenesis. Physical exercise has been considered an effective intervention in AD, attenuating or limiting their progression. Nevertheless, the neurobiological mechanisms underlying the neuroprotective effects of exercise have not yet been fully elucidated. In present study, we investigated the protective effect of an 8-week swimming training (ST) exercise on cognitive and non-cognitive functions and its role in modulating biomarkers of KYN pathway, before an intracerebroventricular (i...
May 11, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28496435/serum-metabolomic-profiling-of-piglets-infected-with-virulent-classical-swine-fever-virus
#9
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
#10
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
#11
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/28488695/blockade-of-ido-kynurenine-ahr-metabolic-circuitry-abrogates-ifn-%C3%AE-induced-immunologic-dormancy-of-tumor-repopulating-cells
#12
Yuying Liu, Xiaoyu Liang, Xiaonan Yin, Jiadi Lv, Ke Tang, Jingwei Ma, Tiantian Ji, Huafeng Zhang, Wenqian Dong, Xun Jin, Degao Chen, Yanchun Li, Songyan Zhang, Heidi Q Xie, Bin Zhao, Tong Zhao, Jinzhi Lu, Zhuo-Wei Hu, Xuetao Cao, F Xiao-Feng Qin, Bo Huang
Interactions with the immune system may lead tumorigenic cells into dormancy. However, the underlying molecular mechanism is poorly understood. Using a 3D fibrin gel model, we show that IFN-γ induces tumour-repopulating cells (TRCs) to enter dormancy through an indolamine 2,3-dioxygenase 1 (IDO1)-kynurenine (Kyn)-aryl hydrocarbon receptor (AhR)-p27 dependent pathway. Mechanistically, IFN-γ signalling triggers differentiated tumour cell apoptosis via STAT1; however, when IDO1 and AhR are highly expressed as in TRCs, IFN-γ results in IDO1/AhR-dependent p27 induction that prevents STAT1 signalling, thus suppressing the process of cell death and activating the dormancy program...
May 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28486923/kynurenic-acid-and-neuroprotective-activity-of-the-ketogenic-diet-in-the-eye
#13
Tomasz Żarnowski, Maria Tulidowicz-Bielak, Iwona Żarnowska, Krystyna Mitosek-Szewczyk, Artur Wnorowski, Krzysztof Jóźwiak, Maciej Gasior, Waldemar A Turski
There is growing evidence of the involvement of the kynurenine metabolic pathway and the enhancement of kynurenic acid (KYNA) production in the neuroprotective effects of the ketogenic diet (KD). KD and ketone bodies (KBs) that are elevated during exposure to the KD each have a neuroprotective effect on retinal ganglion cells in a rat model of N-methyl-D-aspartate (NMDA)-induced neuronal damage. Chronic exposure to KD also increases KYNA concentrations in discrete rat brain structures. A non-selective glutamate receptor agonist, glutamate, also decreases the production of KYNA in bovine retinal slices; this effect is attenuated by acetoacetate and β-hydroxybutyrate, two of three KBs overproduced during KD...
May 9, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28482311/tryptophan-breakdown-and-cognition-in-bipolar-disorder
#14
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/28470889/in-vitro-induction-of-human-regulatory-t-cells-itregs-using-conditions-of-low-tryptophan-plus-kynurenines
#15
K L Hippen, R S O'Connor, A M Lemire, A Saha, E A Hanse, N C Tennis, S C Merkel, A Kelekar, J L Riley, B L Levine, C H June, L S Kean, M L MacMillan, J S Miller, J E Wagner, D H Munn, B R Blazar
Thymic regulatory T cells (tTreg) or induced Tregs (iTregs) suppress murine acute graft-versus-host disease (GVHD). Previously we demonstrated that plasmacytoid dendritic cell (pDC) indoleamine 2,3-dioxygenase (IDO) fosters the in vitro development of human iTregs via tryptophan depletion and kynurenine (Kyn) metabolites. We now show that stimulation of naïve CD4+ T cells in low tryptophan (Low Trp) plus Kyn supports human iTreg generation. In vitro, low Trp+Kyn iTreg and tTregs potently suppress Teffector cell proliferation equivalently but are phenotypically distinct...
May 4, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28469469/tryptophan-metabolism-in-patients-with-chronic-kidney-disease-secondary-to-type-2-diabetes-relationship-to-inflammatory-markers
#16
Subrata Debnath, Chakradhar Velagapudi, Laney Redus, Farook Thameem, Balakuntalam Kasinath, Claudia E Hura, Carlos Lorenzo, Hanna E Abboud, Jason C O'Connor
OBJECTIVE: Type 2 diabetes (T2D) is the primary case of chronic kidney disease (CKD). Inflammation is associated with metabolic dysregulation in patients with T2D and CKD. Tryptophan (TRP) metabolism may have relevance to the CKD outcomes and associated symptoms. We investigated the relationships of TRP metabolism with inflammatory markers in patients with T2D and CKD. METHODS: Data were collected from a well-characterized cohort of type 2 diabetic individuals with all stages of CKD, including patients on hemodialysis...
2017: International Journal of Tryptophan Research: IJTR
https://www.readbyqxmd.com/read/28469468/kynurenine-pathway-of-tryptophan-metabolism-regulatory-and-functional-aspects
#17
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
https://www.readbyqxmd.com/read/28469467/interactions-of-tryptophan-and-its-catabolites-with-melatonin-and-the-alpha-7-nicotinic-receptor-in-central-nervous-system-and-psychiatric-disorders-role-of-the-aryl-hydrocarbon-receptor-and-direct-mitochondria-regulation
#18
REVIEW
George Anderson, Michael Maes
Recent work indicates an intimate interaction of the tryptophan catabolite (TRYCAT) pathways with the melatonergic pathways, primarily via TRYCAT pathway induction taking tryptophan away from the production of serotonin, which is a necessary precursor for the melatonergic pathways. The alpha 7 nicotinic receptor may be significantly modulated by this interaction, given its inactivation by the TRYCAT, kynurenic acid, and its induction by melatonin. Similarly, the aryl hydrocarbon receptor is activated by both kynurenic acid and kynurenine, leading to CYP1A2 and melatonin metabolism, whereas melatonin may act to inhibit the aryl hydrocarbon receptor...
2017: International Journal of Tryptophan Research: IJTR
https://www.readbyqxmd.com/read/28465467/indoleamine-2-3-dioxygenase-1-deficiency-attenuates-ccl4-induced-fibrosis-through-th17-cells-down-regulation-and-tryptophan-2-3-dioxygenase-compensation
#19
Weichao Zhong, Lei Gao, Zhenting Zhou, Haiyan Lin, Chun Chen, Peng Huang, Weiliang Huang, Chuying Zhou, Shaohui Huang, Linghui Nie, Ye Liu, Youming Chen, Daqiao Zhou, Zhiping Lv
Indoleamine 2,3-dioxygenase 1 (IDO1) is an intracellular rate-limiting enzyme in the metabolism of tryptophan along the kynurenine pathway, subsequently mediating the immune response; however, the role of IDO1 in liver fibrosis and cirrhosis is still unclear. In this study, we investigated the role of IDO1 in the development of hepatic fibrosis and cirrhosis. Patients with hepatitis B virus-induced cirrhosis and healthy volunteers were enrolled. For animals, carbon tetrachloride (CCl4) was used to establish liver fibrosis in wild-type and IDO1 knockout mice...
April 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28464785/major-developments-in-the-design-of-inhibitors-along-the-kynurenine-pathway
#20
Kelly R Jacobs, Gloria Castellano Gonzalez, Gilles J Guillemin, David B Lovejoy
Disrupted kynurenine pathway (KP) metabolism has been implicated in the progression of neurodegenerative disease, psychiatric disorders and cancer. Modulation of enzyme activity along this pathway may therefore offer potential new therapeutic strategies for these conditions. Considering their prominent positions in the KP, the enzymes indoleamine 2,3-dioxygenase, kynurenine 3-monooxygenase and kynurenine aminotransferase, appear the most attractive targets. Already, increasing interest in this pathway has led to the identification of a number of potent and selective enzyme inhibitors with promising pre-clinical data and the elucidation of several enzyme crystal structures provides scope to rationalize the molecular mechanisms of inhibitor activity...
May 2, 2017: Current Medicinal Chemistry
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