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Kynurenine

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https://www.readbyqxmd.com/read/28740612/3-hydroxykynurenine-a-tryptophan-metabolite-generated-during-the-infection-is-active-against-trypanosoma-cruzi
#1
Carolina P Knubel, Constanza Insfran, Fernando F Martinez, Cintia Diaz Lujan, Ricardo E Fretes, Martin G Theumer, Laura Cervi, Claudia C Motran
The antiparasitic activity of 3-hydroxykynurenine (3-HK), one of the major tryptophan catabolites of the kynurenine pathway, against both Trypanosoma cruzi evolutive forms that are important for human infection, trypomastigotes (Tps) and amastigotes (Am), possible targets in the parasite and the drug toxicity to mammalian cells have been investigated. 3-HK showed a potent activity against Am with IC50 values in the micromolar concentration range, while the IC50 values to cause Tps death was ∼6000-times higher, indicating that the replicative form present in the vertebrate hosts is much more susceptible to 3-HK than bloodstream Tps...
July 13, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28738373/neuroprogression-in-schizophrenia-and-psychotic-disorders-the-possible-role-of-inflammation
#2
Norbert Müller
Schizophrenia is a disorder that shows a progressive course in 30-50% of the people concerned. The biology of chronification and progression is unclear. Genetic aspects may play a role, but details are unresolved. The fact that immune-mediated and autoimmune disorders such as rheumatoid arthritis or multiple sclerosis have a very similar course as schizophrenia has focused the interest on the immunopathogenesis of schizophrenia. A clear immune marker for neuroprogression in schizophrenia or psychosis could not be identified up to now, but a proinflammatory immune state (increased markers of cellular immunity) is regularly found in schizophrenia, e...
2017: Modern Trends in Pharmacopsychiatry
https://www.readbyqxmd.com/read/28738353/inflammation-effects-on-glutamate-as-a-pathway-to-neuroprogression-in-mood-disorders
#3
Ebrahim Haroon, Andrew H Miller
Neuroprogression is a term used to describe worsening psychopathology, poor treatment response, and declining cognitive and functional outcomes among patients with chronic mental disorders. Chronic inflammatory activation and glutamate-mediated excitotoxicity are two key etiological factors implicated in the development of neuroprogression. In this chapter, we hypothesize that the association between chronic inflammatory activation, neuroprogression, and glutamate dysregulation might be mediated by glial dysfunction...
2017: Modern Trends in Pharmacopsychiatry
https://www.readbyqxmd.com/read/28738351/major-depression-as-a-neuroprogressive-prelude-to-dementia-what-is-the-evidence
#4
Brian E Leonard
Epidemiological studies implicate chronic depression as a predisposing factor for dementia in later life. However, the link is incompletely understood and controversial. The aim of this review is to consider some of the biological factors that contribute to neuroprogressive brain dysfunction in late life as a consequence of prolonged, low-grade inflammation in the course of depressive episodes. As chronic inflammation is known to precipitate increased apoptosis of neurons and astrocytes, this could be a contributing factor to brain dysfunction...
2017: Modern Trends in Pharmacopsychiatry
https://www.readbyqxmd.com/read/28736331/microbial-regulation-of-hippocampal-mirna-expression-implications-for-transcription-of-kynurenine-pathway-enzymes
#5
Gerard M Moloney, Olivia F O'Leary, Eloisa Salvo-Romero, Lieve Desbonnet, Fergus Shanahan, Timothy G Dinan, Gerard Clarke, John F Cryan
Increasing evidence points to a functional role of the enteric microbiota in brain development, function and behaviour including the regulation of transcriptional activity in the hippocampus. No changes in CNS miRNA expression have yet been linked to the colonisation status of the gut. Given the pivotal impact of miRNAs on gene expression, our study was based on the hypothesis that this would also be altered in the germ-free state in the hippocampus. We measured miRNAs in the hippocampus of Germ free (GF), conventional (C) and Germ free colonised (GFC) Swiss Webster mice...
July 20, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28735627/inhibition-of-indoleamine-2-3-dioxygenase-activity-by-fatty-acids-and-prostaglandins-a-structure-function-analysis
#6
M Costabile, N K Bassal, J P Gerber, B P Hughes
Indoleamine 2,3-dioxygenase-1 (IDO-1) catalyses the first and rate-limiting step in the metabolism of L-tryptophan. Degradation of L-Trp leads to the production of several immunosuppressive metabolites, including N-formyl kynurenine and kynurenine (Kyn). Apart from a normal physiological role, IDO-1 has also been identified to play a crucial role in immune suppression and tumour induced tolerance. Indeed, many primary tumours express high levels of IDO-1 compared to normal cells of the same stroma. IDO-1 is accepted as being an inducible negative regulator of T cell viability, proliferation and activation...
July 2017: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/28733707/angiotensin-ii-type-1-receptor-blockers-inhibit-kat-ii-activity-in-the-brain-its-possible-clinical-applications
#7
Izabela Zakrocka, Katarzyna M Targowska-Duda, Artur Wnorowski, Tomasz Kocki, Krzysztof Jóźwiak, Waldemar A Turski
Angiotensin II receptor blockers (ARBs) are one of the most frequently recommended antihypertensive drugs. Apart from their activity towards the circulatory system, ARBs also penetrate the blood-brain barrier and display neuroprotective effects. Kynurenic acid (KYNA) is an endogenous metabolite of tryptophan produced by kynurenine aminotransferase II (KAT II) in the brain. Antagonism towards all ionotropic glutamate (GLU) receptors is the main mechanism of KYNA action. An elevated brain level of KYNA is linked with memory impairment and psychotic symptoms...
July 21, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28733212/the-peroxyl-radical-induced-oxidation-of-escherichia-coli-ftsz-and-its-single-tryptophan-mutant-y222w-modifies-specific-side-chains-generates-protein-cross-links-and-affects-biological-function
#8
Elizabeth Escobar-Álvarez, Fabian Leinisch, Gissela Araya, Octavio Monasterio, Lasse G Lorentzen, Eduardo Silva, Michael J Davies, Camilo López-Alarcón
FtsZ (filamenting temperature-sensitive mutant Z) is a key protein in bacteria cell division. The wild-type Escherichia coli FtsZ sequence (FtsZwt) contains three tyrosine (Tyr, Y) and sixteen methionine (Met, M) residues. The Tyr at position 222 is a key residue for FtsZ polymerization. Mutation of this residue to tryptophan (Trp, W; mutant Y222W) inhibits GTPase activity resulting in an extended time in the polymerized state compared to FtsZwt. Protein oxidation has been highlighted as a determinant process for bacteria resistance and consequently oxidation of FtsZwt and the Y222W mutant, by peroxyl radicals (ROO•) generated from AAPH (2,2'-azobis(2-methylpropionamidine) dihydrochloride) was studied...
July 18, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28731451/novel-blood-based-biomarkers-of-cognition-stress-and-physical-or-cognitive-training-in-older-adults-at-risk-of-dementia-preliminary-evidence-for-a-role-of-bdnf-irisin-and-the-kynurenine-pathway
#9
Olivia C Küster, Daria Laptinskaya, Patrick Fissler, Cathrin Schnack, Martina Zügel, Verena Nold, Franka Thurm, Sina Pleiner, Alexander Karabatsiakis, Björn von Einem, Patrick Weydt, Andre Liesener, Andreas Borta, Alexander Woll, Bastian Hengerer, Iris-Tatjana Kolassa, Christine A F von Arnim
 Psychosocial stress and physical, cognitive, and social activity predict the risk of cognitive decline and dementia. The aim of this study was to elucidate brain-derived neurotrophic factor (BDNF), irisin, and the kynurenine pathway (KP) as potential underlying biological correlates. We evaluated associations of irisin and the KP with BDNF in serum and with cognition, stress, and activities. Furthermore, changes in serum concentrations of BDNF, irisin, and KP metabolites were investigated after physical or cognitive training...
July 18, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28730706/chromatographic-profiles-of-tryptophan-and-kynurenine-enantiomers-derivatized-with-s-4-3-isothiocyanatopyrrolidin-1-yl-7-n-n-dimethylaminosulfonyl-2-1-3-benzoxadiazole-using-lc-ms-ms-on-a-triazole-bonded-column
#10
Hideaki Iizuka, Takahiro Harashima, Shuhei Takahashi, Ryosuke Kuwabara, Yoko Naito, Tatsuya Sakamoto, Mayu Onozato, Hideaki Ichiba, Takeshi Fukushima
d- and l-Tryptophan (Trp) and d- and l-kynurenine (KYN) were derivatized with a chiral reagent, (S)-4-(3-isothiocyanatopyrrolidin-1-yl)-7-(N,N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole (DBD-PyNCS), and were separated enantiomerically by high-performance liquid chromatography (HPLC) equipped with a triazole-bonded column (Cosmosil HILIC) using tandem mass spectrometric (MS/MS) detection. Effects of column temperature, salt (HCO2 NH4 ) concentration, and pH of the mobile phase in the enantiomeric separation, followed by MS detection of (S)-DBD-PyNCS-d,l-Trp and -d,l-KYN, were investigated...
July 21, 2017: Chirality
https://www.readbyqxmd.com/read/28727234/kynurenine-a-tryptophan-metabolite-that-accumulates-with-age-induces-bone-loss
#11
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/28723608/breastfeeding-and-the-gut-brain-axis-is-there-a-role-for-melatonin
#12
REVIEW
George Anderson, Cathy Vaillancourt, Michael Maes, Russel J Reiter
The benefits of breastfeeding over formula feed are widely appreciated. However, for many mothers breastfeeding is not possible, highlighting the need for a significant improvement in the contents of formula feed. In this article, the overlooked role of melatonin and the melatonergic pathways in breast milk and in the regulation of wider breast milk components are reviewed. There is a growing appreciation that the benefits of breastfeeding are mediated by its effects in the infant gut, with consequences for the development of the gut-brain axis and the immune system...
July 19, 2017: Biomolecular Concepts
https://www.readbyqxmd.com/read/28713871/immune-dysfunctionality-of-replicative-senescent-mesenchymal-stromal-cells-is-corrected-by-ifn%C3%AE-priming
#13
Raghavan Chinnadurai, Devi Rajan, Spencer Ng, Kenneth McCullough, Dalia Arafat, Edmund K Waller, Larry J Anderson, Greg Gibson, Jacques Galipeau
Industrial-scale expansion of mesenchymal stromal cells (MSCs) is often used in clinical trials, and the effect of replicative senescence on MSC functionality is of mechanistic interest. Senescent MSCs exhibit cell-cycle arrest, cellular hypertrophy, and express the senescent marker β-galactosidase. Although both fit and senescent MSCs display intact lung-homing properties in vivo, senescent MSCs acquire a significant defect in inhibiting T-cell proliferation and cytokine secretion in vitro. IFNγ does not upregulate HLA-DR on senescent MSCs, whereas its silencing did not reverse fit MSCs' immunosuppressive properties...
April 25, 2017: Blood Advances
https://www.readbyqxmd.com/read/28712531/the-role-of-tryptophan-metabolism-and-food-craving-in-the-relationship-between-obesity-and-bipolar-disorder
#14
N Dalkner, M Platzer, S A Bengesser, A Birner, F T Fellendorf, R Queissner, A Painold, H Mangge, D Fuchs, B Reininghaus, H P Kapfhammer, S J Holasek, E Z Reininghaus
BACKGROUND & AIMS: Individuals with bipolar disorder (BD) have a significantly increased risk of obesity-related conditions. The imbalance between food intake and energy expenditure is assumed to be a major risk factor for obesity in BD. This study analyzed food craving in relation to anthropometric, metabolic, and neurobiological parameters in a well-characterized cohort of euthymic individuals with BD. METHODS: One-hundred-thirty-five patients completed the Food-Craving Inventory assessing four categories of food craving (fat, fast-food, sweets and carbohydrate craving)...
July 4, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28712413/sleep-disturbance-and-kynurenine-metabolism-in-depression
#15
Hyong Jin Cho, Jonathan Savitz, Robert Dantzer, T Kent Teague, Wayne C Drevets, Michael R Irwin
OBJECTIVE: Although the interrelationships between sleep disturbance, inflammation, and depression have been found, molecular mechanisms that link these conditions are largely unknown. Kynurenine metabolism is hypothesized to be a key mechanism that links inflammation and depression. Inflammation activates the kynurenine pathway, leading to increases in 3-hydroxykynurenine (3HK) and quinolinic acid (QA), potentially neurotoxic metabolites, and decreases in kynurenic acid (KynA), a potentially neuroprotective compound...
August 2017: Journal of Psychosomatic Research
https://www.readbyqxmd.com/read/28711496/metabolomic-profiling-reveals-potential-biomarkers-in-esophageal-cancer-progression-using-liquid-chromatography-mass-spectrometry-platform
#16
Haiping Zhang, Lei Wang, Zhichao Hou, Hong Ma, Batur Mamtimin, Ayshamgul Hasim, Ilyar Sheyhidin
Esophageal cancer (EC) is one of the most common malignancies with poor prognosis. Metabolomics has been shown to be a powerful approach to discover the potential biomarkers for cancer diagnosis and prognosis. The goal of this study is to screen potential biomarkers for early diagnosis and prognosis. In this study, 40 tissue samples and the corresponding control samples from the same esophageal squamous cell carcinoma (ESCC) patients were analyzed by liquid chromatography-mass spectrometry (LC-MS)-based metabolomics...
July 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28710517/urinary-profiling-of-tryptophan-and-its-related-metabolites-in-patients-with-metabolic-syndrome-by-liquid-chromatography-electrospray-ionization-mass-spectrometry
#17
Ji Sun Oh, Hong Seong Seo, Kyoung Heon Kim, Heesoo Pyo, Bong Chul Chung, Jeongae Lee
Tryptophan (Trp) is an essential amino acid that plays an important role in protein synthesis and is a precursor of various substances related to diverse biological functions. An imbalance in Trp metabolites is associated with inflammatory diseases. The accurate and precise measurement of these compounds in biological specimens would provide meaningful information for understanding the biochemical states of various metabolic syndrome-related diseases, such as hyperlipidemia, hypertension, diabetes, and obesity...
July 14, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28709913/upregulation-of-neuronal-kynurenine-3-monooxygenase-mediates-depression-like-behavior-in-a-mouse-model-of-neuropathic-pain
#18
Geoffroy Laumet, Wenjun Zhou, Robert Dantzer, Jules D Edralin, XiaoJiao Huo, David P Budac, Jason C O'Connor, Anna W Lee, Cobi J Heijnen, Annemieke Kavelaars
Pain and depression often co-occur, but the underlying mechanisms have not been elucidated. Here, we used the spared nerve injury (SNI) model in mice to induce both neuropathic pain and depression-like behavior. We investigated whether brain IL-1 signaling and activity of kynurenine 3-monoxygenase (KMO), a key enzyme for metabolism of kynurenine into the neurotoxic NMDA receptor agonist quinolinic acid, are necessary for comorbid neuropathic pain and depression-like behavior. SNI mice showed increased expression levels of Il1b and Kmo mRNA in the contralateral side of the brain...
July 11, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28706436/the-presence-of-kynurenine-aminotransferases-in-the-human-cornea-evidence-from-bioinformatics-analysis-of-gene-expression-and-immunohistochemical-staining
#19
Anna Matysik-Woźniak, Anselm Jünemann, Waldemar A Turski, Artur Wnorowski, Krzysztof Jóźwiak, Roman Paduch, Etsuo Okuno, Joanna Moneta-Wielgoś, Tomasz Chorągiewicz, Ryszard Maciejewski, Robert Rejdak
PURPOSE: Kynurenine aminotransferases (KATs) catalyze the synthesis of kynurenic acid (KYNA), a compound of significant biological activity. The aim of this study is to investigate the presence and distribution of KAT immunoreactivity in the healthy human cornea. METHODS: Data on gene expression in human eye structures were extracted from public microarray experiments using Genevestigator software. Immunohistochemistry was conducted using polyclonal antibodies against KAT I, II, and III on sections of eight enucleated eyes from patients with choroidal melanoma...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28705908/importance-of-kynurenine-in-pulmonary-hypertension
#20
Bence M Nagy, Chandran Nagaraj, Andreas Meinitzer, Neha Sharma, Rita Papp, Vasile Foris, Bahil Ghanim, Grazyna Kwapiszewska, Gabor Kovacs, Walter Klepetko, Thomas R Pieber, Harald Mangge, Horst Olschewski, Andrea Oslchewski
The tryptophan metabolite kynurenine is significantly increased in pulmonary arterial hyper-tension (PAH) patients, and it is a potent vasodilator of systemic arteries. Our aim was to in-vestigate the role of kynurenine in the pulmonary circulation. Serum tryptophan, kynurenine and kynurenic-acid levels were measured in 20 idiopathic PAH (IPAH) patients, 20 healthy controls and 20 patients with chronic lung disease or meta-bolic syndrome without-PH. Laser-dissected pulmonary arteries from IPAH and control lungs were tested for the expression of IDO, the rate-limiting enzyme for the conversion from tryptophan to kynurenine...
July 13, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
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