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https://www.readbyqxmd.com/read/29343967/indoleamine-2-3-dioxygenase-activity-increases-nad-production-in-ifn-%C3%AE-stimulated-human-primary-mononuclear-cells
#1
Ross S Grant
IFN-γ activation of mononuclear phagocytes significantly increases indoleamine 2,3-dioxygenase (IDO) and flux through the kynurenine pathway (KP). However, the effect of IDO on NAD+ synthesis, the end product of KP metabolism, is unknown. To investigate this, primary human peripheral blood mononuclear cells were cultured up to 10 days and activated with IFN-γ in the presence or absence of a poly(ADP-ribose) polymerase (PARP) inhibitor. Day 10 macrophages had significantly higher NAD+ levels compared with monocytes...
2018: International Journal of Tryptophan Research: IJTR
https://www.readbyqxmd.com/read/29342113/mitochondria-oxidative-stress-and-the-kynurenine-system-with-a-focus-on-ageing-and-neuroprotection
#2
REVIEW
Katalin Sas, Elza Szabó, László Vécsei
In this review, the potential causes of ageing are discussed. We seek to gain insight into the main physiological functions of mitochondria and discuss alterations in their function and the genome, which are supposed to be the central mechanisms in senescence. We conclude by presenting the potential modulating role of the kynurenine pathway in the ageing processes. Mitochondrial dynamics are supposed to have important physiological roles in maintaining cell homeostasis. During ageing, a decrease in mitochondrial dynamics was reported, potentially compromising the function of mitochondria...
January 17, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29327354/a-validated-liquid-chromatography-high-resolution-tandem-mass-spectrometry-method-for-the-simultaneous-quantitation-of-tryptophan-kynurenine-kynurenic-acid-and-quinolinic-acid-in-human-plasma
#3
Kathrin Arnhard, Florian Pitterl, Barbara Sperner-Unterweger, Dietmar Fuchs, Therese Koal, Herbert Oberacher
Tryptophan (TRP) catabolism via the kynurenine pathway is considered to represent a major link between inflammation and various diseases, including neurodegenerative disorders, depression, schizophrenia, multiple sclerosis, cardiovascular disease, and cancer. The kynurenine pathway and levels of TRP and its metabolites kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QUIN) are well regulated under physiological conditions but may be altered as part of the activated immune response. A simple, sensitive and specific liquid chromatography-time of flight mass spectrometry method was developed for determining levels of the four compounds in human plasma samples...
January 12, 2018: Electrophoresis
https://www.readbyqxmd.com/read/29320557/high-ahr-expression-in-breast-tumors-correlates-with-expression-of-genes-from-several-signaling-pathways-namely-inflammation-and-endogenous-tryptophan-metabolism
#4
Sophie Vacher, Patrice Castagnet, Walid Chemlali, François Lallemand, Didier Meseure, Marc Pocard, Ivan Bieche, Martine Perrot-Applanat
Increasing epidemiological and animal experimental data provide substantial support for the role of aryl hydrocarbon receptor (AhR) in mammary tumorigenesis. The effects of AhR have been clearly demonstrated in rodent models of breast carcinogenesis and in several established human breast cancer cell lines following exposure to AhR ligands or AhR overexpression. However, relatively little is known about the role of AhR in human breast cancers. AhR has always been considered to be a regulator of toxic and carcinogenic responses to environmental contaminants such as TCDD (dioxin) and benzo[a]pyrene (BaP)...
2018: PloS One
https://www.readbyqxmd.com/read/29317240/toxicity-and-cardiac-effects-of-acute-exposure-to-tryptophan-metabolites-on-the-kynurenine-pathway-in-early-developing-zebrafish-danio-rerio-embryos
#5
Michal Majewski, Natalia Kasica, Anna Jakimiuk, Piotr Podlasz
Defects in tryptophan metabolism on the l-kynurenine pathway (KP) are implicated in a number of human diseases, including chronic kidney disease, brain edema or injury, tuberculosis and malaria - as well as cancer, neurodegenerative and autoimmune disorders. However, it is unclear to what extent detrimental effects of exposure to tryptophan metabolites might impact the early development of organism. Thus, this study examined the effects of KP exposure in zebrafish embryos starting at the blastula period (4hpf) and the segmentation stage (24hpf)...
January 6, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29307018/the-role-of-tryptophan-metabolism-in-postpartum-depression
#6
REVIEW
Kai-Ming Duan, Jia-Hui Ma, Sai-Ying Wang, ZhengDong Huang, YingYong Zhou, HeYa Yu
The Postpartum depression (PPD) is the most common postpartum psychiatric disorder, afflicting approximately 10%-20% of new mothers. Clinical symptoms of the PPD include depressive disorder, agitation, insomnia, anxiety and confusion, resulting in an increase in suicidal tendencies, thereby having significant impacts on the puerpera, newborn and their family. A growing body of data indicate a role for alterations in tryptophan metabolism in the PPD. The metabolism of tryptophan produces an array of crucial factors that can differentially regulate key physiological processes linked to the PPD...
January 6, 2018: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29301550/role-of-the-indoleamine-2-3-dioxygenase-kynurenine-pathway-of-tryptophan-metabolism-in-behavioral-alterations-in-a-hepatic-encephalopathy-rat-model
#7
Xi Jiang, Lexing Xu, Lin Tang, Fuhe Liu, Ziwei Chen, Jiajia Zhang, Lei Chen, Cong Pang, Xuefeng Yu
BACKGROUND: This study aims to explore the role of indoleamine-2,3-dioxygenase (IDO)/kynurenine (KYN) pathway of tryptophan (TRY) metabolism in behavioral alterations observed in hepatic encephalopathy (HE) rats. METHODS: Expression levels of proinflammatory cytokines were tested by QT-PCR and ELISA, levels of IDOs were tested by QT-PCR and Western blot, and levels of 5-hydroxytryptamine (5-HT), KYN, TRY, 3-hydroxykynurenine (3-HK), and kynurenic acid (KA) in different brain regions were estimated using HPLC...
January 4, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29275469/tryptophan-catabolism-and-cancer-immunotherapy-targeting-ido-mediated-immune-suppression
#8
Adaobi Amobi, Feng Qian, Amit A Lugade, Kunle Odunsi
Over the last decade, tryptophan catabolism has been firmly established as a powerful mechanism of innate and adaptive immune tolerance. The catabolism of tryptophan is a central pathway maintaining homeostasis by preventing autoimmunity or immunopathology that would result from uncontrolled and overreacting immune responses. This is driven by the key and rate-limiting enzymes indoleamine-2,3-dioxygenase 1 (IDO1) and tryptophan-2,3-dioxygenase 2 (TDO), resulting in local depletion of tryptophan, while tryptophan catabolites accumulate, including kynurenine and its derivatives, depending on the presence of downstream enzymes in the kynurenine pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29242525/inhibition-of-human-kynurenine-aminotransferase-isozymes-by-estrogen-and-its-derivatives
#9
Gayan S Jayawickrama, Alireza Nematollahi, Guanchen Sun, Mark D Gorrell, W Bret Church
The kynurenine aminotransferase (KAT) enzymes are pyridoxal 5'-phosphate-dependent homodimers that catalyse the irreversible transamination of kynurenine into kynurenic acid (KYNA) in the tryptophan metabolic pathway. Kynurenic acid is implicated in cognitive diseases such as schizophrenia, and several inhibitors have been reported that selectively target KAT-II as it is primarily responsible for kynurenic acid production in the human brain. Not only is schizophrenia a sexually dimorphic condition, but women that have schizophrenia have reduced estrogen levels in their serum...
December 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29241670/glia-and-tissue-specific-changes-in-the-kynurenine-pathway-after-treatment-of-mice-with-lipopolysaccharide-and-dexamethasone
#10
Carlos R Dostal, Nicolaus S Gamsby, Marcus A Lawson, Robert H McCusker
Behavioral symptoms associated with mood disorders have been intimately linked with immunological and psychological stress. Induction of immune and stress pathways is accompanied by increased tryptophan entry into the Kynurenine (Kyn) Pathway as governed by the rate-limiting enzymes indoleamine/tryptophan 2,3-dioxygenases (DO's: Ido1, Ido2, Tdo2). Indeed, elevated DO expression is associated with inflammation- and stress-related depression symptoms. Here we examined central (brain, astrocyte and microglia) and peripheral (lung, liver and spleen) DO expression in mice treated intraperitoneally with lipopolysaccharide (LPS) and dexamethasone (DEX) to model the response of the Kyn Pathway to inflammation and glucocorticoids...
December 11, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29235064/induction-of-neuroinflammatory-response-and-histopathological-alterations-caused-by-quinolinic-acid-administration-in-the-striatum-of-glutaryl-coa-dehydrogenase-deficient-mice
#11
Alexandre Umpierrez Amaral, Bianca Seminotti, Janaína Camacho da Silva, Francine Hehn de Oliveira, Rafael Teixeira Ribeiro, Carmen Regla Vargas, Guilhian Leipnitz, Abel Santamaría, Diogo Onofre Souza, Moacir Wajner
Glutaric acidemia type I (GA I) is an inherited neurometabolic disorder caused by a severe deficiency of the mitochondrial glutaryl-CoA dehydrogenase (GCDH) activity. Patients usually present progressive cortical leukodystrophy and commonly develop acute bilateral striatal degeneration mainly during infections that markedly worse their prognosis. A role for quinolinic acid (QA), a key metabolite of the kynurenine pathway, which is activated during inflammatory processes, on the pathogenesis of the acute striatum degeneration occurring in GA I was proposed but so far has not yet been evaluated...
December 12, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29233180/distinct-cytokine-patterns-may-regulate-the-severity-of-neonatal-asphyxia-an-observational-study
#12
Anna Bajnok, László Berta, Csaba Orbán, Gábor Veres, Dénes Zádori, Hajnalka Barta, Ünőke Méder, László Vécsei, Tivadar Tulassay, Miklós Szabó, Gergely Toldi
BACKGROUND: Neuroinflammation and a systemic inflammatory reaction are important features of perinatal asphyxia. Neuroinflammation may have dual aspects being a hindrance, but also a significant help in the recovery of the CNS. We aimed to assess intracellular cytokine levels of T-lymphocytes and plasma cytokine levels in moderate and severe asphyxia in order to identify players of the inflammatory response that may influence patient outcome. METHODS: We analyzed the data of 28 term neonates requiring moderate systemic hypothermia in a single-center observational study...
December 12, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29224960/persons-with-secondary-progressive-and-relapsing-remitting-multiple-sclerosis-reveal-different-responses-of-tryptophan-metabolism-to-acute-endurance-exercise-and-training
#13
Jens Bansi, Christina Koliamitra, Wilhelm Bloch, Niklas Joisten, Alexander Schenk, Matthew Watson, Jan Kool, Dawn Langdon, Ulrik Dalgas, Jürg Kesselring, Philipp Zimmer
Disturbances in Tryptophan metabolism play a crucial role in multiple sclerosis (MS). Exercise is suspected to counteract the progress of MS and its side effects. Current research suggests alterations of Tryptophan metabolism in healthy individuals in response to exercise. We investigated the influence of acute aerobic exercise and training on Tryptophan metabolism in 57 inpatients with relapsing remitting ((RRMS) n=33) and secondary progressive ((SPMS) n=24) MS. Serotonin increased after training, whereas the kynurenine pathway was only activated in persons with RRMS...
December 6, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29217180/structure-based-mimicking-of-phthalic-acid-esters-paes-and-inhibition-of-hacmsd-an-important-enzyme-of-the-tryptophan-kynurenine-metabolism-pathway
#14
Neha Singh, Vikram Dalal, Pravindra Kumar
Human α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (hACMSD) is a zinc containing amidohydrolase which is a vital enzyme of the kynurenine pathway in tryptophan metabolism. It prevents the accumulation of quinolinic acid (QA) and helps in the maintenance of basal trp-niacin ratio. To assess the structure based inhibitory action of PAEs such as DMP, DEP, DBP, DIBP, DEHP and their metabolites, these were docked into the active site cavity of hACMSD. Docking results show that the binding affinities of PAEs lie in the comparable range (-4...
December 4, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29208371/integrated-semi-targeted-metabolomics-analysis-reveals-distinct-metabolic-dysregulation-in-pleural-effusion-caused-by-tuberculosis-and-malignancy
#15
Nanying Che, Yan Ma, Huabin Ruan, Lina Xu, Xueying Wang, Xinting Yang, Xiaohui Liu
BACKGROUND: Tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) are the 2 most frequent causes of exudative pleural effusions (PEs). However, the clinical differentiation is challenging. METHODS: Metabolic signatures in pleural effusion from 156 patients were profiled. An integrated semi-targeted metabolomics platform was incorporated for high throughput metabolite identification and quantitation. In this platform, orbitrap based mass spectrometry with data dependent MS/MS acquisition was applied in the analysis...
December 5, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29195782/hmgb1-mediates-depressive-behavior-induced-by-chronic-stress-through-activating-the-kynurenine-pathway
#16
Bo Wang, Yong-Jie Lian, Wen-Jun Su, Wei Peng, Xin Dong, Lin-Lin Liu, Hong Gong, Ting Zhang, Chun-Lei Jiang, Yun-Xia Wang
Our previous study has reported that the proactive secretion and role of central high mobility group box 1 (HMGB1) in lipopolysaccharide-induced depressive behavior. Here, the potential mechanism of HMGB1 mediating chronic-stress-induced depression through the kynurenine pathway (KP) was further explored both in vivo and in vitro. Depression model was established with the 4-week chronic unpredictable mild stress (CUMS). Sucrose preference and Barnes maze test were performed to reflect depressive behaviors. The ratio of kynurenine (KYN)/tryptophan (Trp) represented the enzyme activity of indoleamine-2,3-dioxygenase (IDO)...
November 28, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29163472/the-kynurenine-pathway-as-a-novel-link-between-allergy-and-the-gut-microbiome
#17
REVIEW
Aaron P Van der Leek, Yarden Yanishevsky, Anita L Kozyrskyj
In the past few decades, the indoleamine 2,3 dioxygenase (IDO) subset of the kynurenine (KYN) pathway of tryptophan (TRP) metabolism has been the subject of much research in the area of immune tolerance. In this review, we aim to incorporate new findings on this pathway in relation to allergy and the gut microbiome, while providing a comprehensive overview of the pathway itself. Stimulated by interferon gamma, IDO acts as a tolerogenic, immunosuppressive enzyme to attenuate allergic responses by the induction of the KYN-IDO pathway, resultant depletion of TRP, and elevation in KYN metabolites...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163188/elevated-levels-of-peripheral-kynurenine-decrease-bone-strength-in-rats-with-chronic-kidney-disease
#18
Bartlomiej Kalaska, Krystyna Pawlak, Tomasz Domaniewski, Ewa Oksztulska-Kolanek, Beata Znorko, Alicja Roszczenko, Joanna Rogalska, Malgorzata M Brzoska, Pawel Lipowicz, Michal Doroszko, Anna Pryczynicz, Dariusz Pawlak
The diagnosis and treatment of bone disorders in patients with chronic kidney disease (CKD) represent a clinical challenge. CKD leads to mineral and bone complications starting early in the course of renal failure. Recently, we have observed the positive relationship between intensified central kynurenine turnover and bone strength in rats with subtotal 5/6 nephrectomy (5/6 Nx)-induced CKD. The aim of the present study was to determine the association between peripheral kynurenine pathway metabolites and bone strength in rats with 5/6 Nx-induced CKD...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29155324/angiotensin-receptor-blocker-irbesartan-reduces-stress-induced-intestinal-inflammation-via-at1a-signaling-and-ace2-dependent-mechanism-in-mice
#19
Maimaiti Yisireyili, Yasuhiro Uchida, Koji Yamamoto, Takayuki Nakayama, Xian Wu Cheng, Tadashi Matsushita, Shigeo Nakamura, Toyoaki Murohara, Kyosuke Takeshita
Stress is associated with pathophysiology of both irritable bowel syndrome (IBS) and hypertension. Angiotensin receptor blockers (ARB) have anti-inflammatory properties via inhibition of angiotensin II (Ang II)/Ang II type I receptor axis (AT1). Inhibition of the classical RAS pathway is also involved in upregulation of angiotensin converting enzyme-2 (ACE2), which activates the Ang-(1-7)/Mas pathway to counteract inflammatory signaling and acts as a partner of the amino acid transporter, B0AT-1, to absorb tryptophan for regulation of microbiota-gut-brain axis...
November 16, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29154397/effects-of-high-ambient-temperature-on-plasma-metabolomic-profiles-in-chicks
#20
Shozo Tomonaga, Hirofumi Okuyama, Tetsuya Tachibana, Ryosuke Makino
Exposure to high ambient temperature is detrimental to the poultry industry. To understand the influence from a metabolic perspective, we investigated the effects of exposure to high ambient temperature on plasma low-molecular-weight metabolite levels in chicks using gas chromatography/mass spectrometry-based non-targeted metabolomic analysis. Heat exposure for 4 days suppressed growth and food intake. Of the 92 metabolites identified, the levels of 29 decreased, whereas the levels of nine increased. We performed an enrichment analysis on the identified metabolites and found 35 candidates for metabolic processes affected by heat exposure...
November 20, 2017: Animal Science Journal, Nihon Chikusan Gakkaihō
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