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Shrestha Priyadarsini, Tina B McKay, Akhee Sarker-Nag, Jeremy Allegood, Charles Chalfant, Jian-Xing Ma, Dimitrios Karamichos
Prolonged hyperglycemia during diabetes mellitus can cause severe ophthalmic complications affecting both the anterior and posterior ocular segments leading to impaired vision or blindness. Diabetes-induced corneal pathologies are associated with decreased wound healing capacity, corneal edema, and altered epithelial basement membrane. The mechanism by which diabetes modulates structure and function within the corneal stroma are unknown. In our study, we characterized the effects of diabetes on extracellular matrix, lipid transport, and cellular metabolism by defining the entire metabolome and lipidome of Type 1 and Type 2 human diabetic corneal stroma...
October 11, 2016: Experimental Eye Research
G Oxenkrug, J Cornicelli, M van der Hart, J Roeser, P Summergrad
Obesity is an increasingly urgent global problem and the molecular mechanisms of obesity are not fully understood. Dysregulation of the tryptophan (Trp) - kynurenine (Kyn) metabolic pathway (TKP) have been suggested as a mechanism of obesity and described in obese humans and in animal models of obesity. However, to the best of our knowledge, TKP metabolism has not been studied in leptin-receptor-deficient Zucker fatty rats (ZFR) (fa/fa), the best-known and most widely used rat model of obesity. We were interested to determine if there are any deviations of TKP in ZFR...
2016: Integrative Molecular Medicine
Sally A Abuelezz, Nevien Hendawy, Yosra Magdy
Depression is a major health problem in which oxidative stress and inflammation are inextricably connected in its pathophysiology. Coenzyme Q10 (CoQ10) is an important anti-oxidant compound with anti-inflammatory and neuro-protective properties. This study was designed to investigate the hypothesis that CoQ10 by its anti-oxidant and anti-inflammatory potentials can alleviate depressive- like behavior by restoring the balance of the tryptophan catabolites kynurenine/serotonin toward the serotonin pathway by down-regulation of hippocampal indoleamine 2,3-dioxygenase 1 (IDO-1)...
October 11, 2016: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Øivind Midttun, Adrian McCann, Ove Aarseth, Marit Krokeide, Gry Kvalheim, Klaus Meyer, Per Magne Ueland
Targeted metabolic profiling characterized by complementary platforms, multiplexing and low volume consumption are increasingly used for studies using biobank material. Using liquid-liquid extraction, we developed a sample workup suitable for quantification of 6 fat- and 26 water-soluble biomarkers. 50μL of serum/plasma was mixed with dithioerythritol, ethanol and isooctane/chloroform. The organic layer was used for analysis of the fat-soluble vitamins all-trans retinol (A), 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, α-tocopherol (E), γ-tocopherol (E) and phylloquinone (K1) by LC-MS/MS...
October 7, 2016: Analytical Chemistry
Elisa Albini, Verdiana Rosini, Marco Gargaro, Giada Mondanelli, Maria L Belladonna, Maria Teresa Pallotta, Claudia Volpi, Francesca Fallarino, Antonio Macchiarulo, Cinzia Antognelli, Roberta Bianchi, Carmine Vacca, Paolo Puccetti, Ursula Grohmann, Ciriana Orabona
The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) catalyses the initial, rate-limiting step in tryptophan (Trp) degradation, resulting in tryptophan starvation and the production of immunoregulatory kynurenines. IDO1's catalytic function has long been considered as the one mechanism responsible for IDO1-dependent immune suppression by dendritic cells (DCs), which are master regulators of the balance between immunity and tolerance. However, IDO1 also harbours immunoreceptor tyrosine-based inhibitory motifs, (ITIM1 and ITIM2), that, once phosphorylated, bind protein tyrosine phosphatases, (SHP-1 and SHP-2), and thus trigger an immunoregulatory signalling in DCs...
September 30, 2016: Journal of Cellular and Molecular Medicine
Tomoyuki Tashiro, Yuki Murakami, Akihiro Mouri, Yukio Imamura, Toshitaka Nabeshima, Yasuko Yamamoto, Kuniaki Saito
l-Tryptophan (TRP) is metabolized via serotonin and kynurenine pathways (KP). Several studies have demonstrated that abnormality of both pathways is involved in the pathogenesis of major depressive disorder (MDD). Kynurenine 3-monooxygenase (KMO), a pivotal enzyme in the KP, has been suggested to play major roles in physiological and pathological events mediated by bioactive kynurenine metabolites. In this study, we investigated the role of KMO in the emotional and cognitive functions by using KMO knockout (KO) mice...
September 28, 2016: Behavioural Brain Research
E Kaczorek, J Szarek, M Mikiewicz, E Terech-Majewska, P Schulz, J Małaczewska, R Wójcik, A K Siwicki
Kynurenic acid (KYNA) is an endogenous substance produced on the kynurenine pathway which is primarily known for its neuroactive properties. Recently, it has been proven that KYNA is a selective ligand for G protein-coupled receptor (GPR 35), presented on immunocompetent cells such as T lymphocytes. This opens up new possibilities of its application as an immunostimulating substance in aquaculture. Thus far, no histopathological investigations in fish have been completed to evaluate influence of KYNA supplementation in feed...
September 30, 2016: Journal of Fish Diseases
Richard L Guerrant, Alvaro M Leite, Relana Pinkerton, Pedro H Q S Medeiros, Paloma A Cavalcante, Mark DeBoer, Margaret Kosek, Christopher Duggan, Andrew Gewirtz, Jonathan C Kagan, Anna E Gauthier, Jonathan Swann, Jordi Mayneris-Perxachs, David T Bolick, Elizabeth A Maier, Marjorie M Guedes, Sean R Moore, William A Petri, Alexandre Havt, Ila F Lima, Mara de Moura Gondim Prata, Josyf C Michaleckyj, Rebecca J Scharf, Craig Sturgeon, Alessio Fasano, Aldo A M Lima
Critical to the design and assessment of interventions for enteropathy and its developmental consequences in children living in impoverished conditions are non-invasive biomarkers that can detect intestinal damage and predict its effects on growth and development. We therefore assessed fecal, urinary and systemic biomarkers of enteropathy and growth predictors in 375 6-26 month-old children with varying degrees of malnutrition (stunting or wasting) in Northeast Brazil. 301 of these children returned for followup anthropometry after 2-6m...
2016: PloS One
Mohammad-Ali Jenabian, Cecilia T Costiniuk, Vikram Mehraj, Feras M Ghazawi, Rémi Fromentin, Joëlle Brousseau, Pierre Brassard, Maud Bélanger, Petronela Ancuta, Reina Bendayan, Nicolas Chomont, Jean-Pierre Routy
OBJECTIVE: HIV persistence in long-lived infected cells and in anatomical sanctuary sites are major hurdles to HIV eradication. Testicular tissue may represent a significant viral sanctuary site as it constitutes an immunologically-privileged compartment. We assessed immuno-tolerance properties of the testicular tissue in individuals receiving suppressive ART. DESIGN AND METHODS: Testicular tissue and matched blood samples were collected from 6 virally suppressed adults and 10 HIV-uninfected controls prior to gender reassignment surgery...
September 24, 2016: AIDS
Christos Skouras, Xiaozhong Zheng, Margaret Binnie, Natalie Z M Homer, Toby B J Murray, Darren Robertson, Lesley Briody, Finny Paterson, Heather Spence, Lisa Derr, Alastair J Hayes, Andreas Tsoumanis, Dawn Lyster, Rowan W Parks, O James Garden, John P Iredale, Iain J Uings, John Liddle, Wayne L Wright, George Dukes, Scott P Webster, Damian J Mole
Inhibition of kynurenine 3-monooxygenase (KMO) protects against multiple organ dysfunction (MODS) in experimental acute pancreatitis (AP). We aimed to precisely define the kynurenine pathway activation in relation to AP and AP-MODS in humans, by carrying out a prospective observational study of all persons presenting with a potential diagnosis of AP for 90 days. We sampled peripheral venous blood at 0, 3, 6, 12, 24, 48, 72 and 168 hours post-recruitment. We measured tryptophan metabolite concentrations and analysed these in the context of clinical data and disease severity indices, cytokine profiles and C-reactive protein (CRP) concentrations...
September 27, 2016: Scientific Reports
Theodoros Eleftheriadis, Georgios Pissas, Maria Sounidaki, Konstantina Tsogka, Nikolaos Antoniadis, Georgia Antoniadi, Vassilios Liakopoulos, Ioannis Stefanidis
Indoleamine 2,3-dioxygenase (IDO) is expressed in antigen-presenting cells and by degrading L-tryptophan along the kynurenine pathway suppresses CD4+ T-cell proliferation, induces apoptosis and promotes differentiation towards a regulatory as opposed to an effector phenotype. Recent findings revealed that the above effects may be mediated through alterations in T-cell metabolism. In this study, the effect of IDO on fatty acid β-oxidation in CD4+ T-cells was evaluated in human mixed lymphocyte reactions (MLRs) using the IDO inhibitor, 1-DL-methyl-tryptophan...
September 23, 2016: International Journal of Molecular Medicine
Juan Manuel Chao de la Barca, Oussama Bakhta, Hussein Kalakech, Gilles Simard, Sophie Tamareille, Véronique Catros, Jacques Callebert, Cédric Gadras, Lydie Tessier, Pascal Reynier, Fabrice Prunier, Delphine Mirebeau-Prunier
BACKGROUND: Remote ischemic preconditioning (RIPC) is an attractive therapeutic procedure for protecting the heart against ischemia/reperfusion injury. Despite evidence of humoral mediators transported through the circulation playing a critical role, their actual identities so far remain unknown. We sought to identify plasmatic RIPC-induced metabolites that may play a role. METHODS AND RESULTS: Rat plasma samples from RIPC and control groups were analyzed using a targeted metabolomic approach aimed at measuring 188 metabolites...
2016: Journal of the American Heart Association
Ana Laura Colín-González, Gabriela Aguilera, Abel Santamaría
The endocannabinoid system (ECS) comprises a complex of receptors, enzymes, and endogenous agonists that are widely distributed in the central nervous system of mammals and participates in a considerable number of neuromodulatory functions, including neurotransmission, immunological control, and cell signaling. In turn, the kynurenine pathway (KP) is the most relevant metabolic route for tryptophan degradation to form the metabolic precursor NAD(+). Recent studies demonstrate that the control exerted by the pharmacological manipulation of the ECS on the glutamatergic system in the brain may offer key information not only on the development of psychiatric disorders like psychosis and schizophrenia-like symptoms, but it also may constitute a solid basis for the development of therapeutic strategies to combat excitotoxic events occurring in neurological disorders like Huntington's disease (HD)...
2016: Advances in Neurobiology
Jaya Prakash Chalise, Maria Teresa Pallotta, Sudeep Chenna Narendra, Björn Carlsson, Alberta Iacono, Joanitah Namale, Louis Boon, Ursula Grohmann, Mattias Magnusson
IFN-α prevents Ag-induced arthritis (AIA), and in this study we investigated the role of IDO1 and TGF-β signaling for this anti-inflammatory property of IFN-α. Arthritis was induced by methylated BSA (mBSA) in mBSA-sensitized wild-type (WT), Ido1(-/-), or Ifnar(-/-) mice, treated or not with IFN-α or the IDO1 product kynurenine (Kyn). Enzymatic IDO1 activity, TGF-β, and plasmacytoid dendritic cells (pDC) were neutralized by 1-methyltryptophan and Abs against TGF-β and pDC, respectively. IDO1 expression was determined by RT-PCR, Western blot, and FACS, and enzymatic activity by HPLC...
September 19, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Yue Zhang, Yizhe Ruan, Ping Zhang, Li Wang
AIM: The study aimed to test the hypothesis that indoleamine 2,3-dioxygenase (IDO) plays a pathogenic role in type 2 diabetic nephropathy (DN). METHODS: One hundred individuals were recruited in our study from January 2012 to December 2013, including group A (control group, 24 healthy adults), group B (20 patients with latent glomerulonephritis), group C (32 type 2 DN patients, estimated glomerular filtration rate (eGFR) >30ml/min per 1.73m(2)), group D (24 maintenance hemodialysis, MHD patients)...
August 28, 2016: Journal of Diabetes and its Complications
Eunsoo Won, Yong-Ku Kim
The autonomic nervous system is one of the major neural pathways activated by stress. In situations that are often associated with chronic stress, such as major depressive disorder, the sympathetic nervous system can be continuously activated without the normal counteraction of the parasympathetic nervous system. As a result, the immune system can be activated with increased levels of proinflammatory cytokines. These inflammatory conditions have been repeatedly observed in depression. In the search for the mechanism by which the immune system might contribute to depression, the enhanced activity of indoleamine 2,3- dioxygenase by pro-inflammatory cytokines has been suggested to play an important role...
2016: Current Neuropharmacology
Birgitte Stiksrud, Kristina Berg Lorvik, Dag Kvale, Tom Eirik Mollnes, Per Magne Ueland, Marius Trøseid, Kjetil Taskén, Anne M Dyrhol-Riise
OBJECTIVE: To explore immune mechanisms and identify biomarkers associated with an inadequate immune recovery in patients with HIV with efficient antiretroviral therapy. DESIGN: A cross-sectional study of 67 HIV-infected patients on antiretroviral therapy for ≥24 months with HIV RNA ≤20 copies per milliliter; 41 were defined as immunological nonresponders (INR) (CD4 < 400 cells per microliter) and 26 as immunological responders (CD4 > 600 cells per microliter)...
October 1, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Pascal Barat, Marie-Claire Meiffred, Julie Brossaud, Dietmar Fuchs, Jean-Benoit Corcuff, Helene Thibault, Lucile Capuron
Alterations in endocrine functions and low-grade systemic inflammation represent fundamental characteristics of obesity. These biological systems have been repeatedly linked to fatigue symptoms. The aim of the study was to assess the relationship between fatigue dimensions and metabolic/inflammatory markers in a sample of non-diabetic obese children. The possibility that inflammation-induced alterations in tryptophan metabolism relates to specific dimensions of fatigue was also investigated in a subsample of patients...
September 8, 2016: Psychoneuroendocrinology
Ashwin Jacob Mathai, Jyoti Kanwar, Olaoluwa Okusaga, Dietmar Fuchs, Christopher A Lowry, Xiaoqing Peng, Ina Giegling, Annette M Hartmann, Bettina Konte, Marion Friedl, Claudia Gragnoli, Gloria M Reeves, Maureen W Groer, Richard N Rosenthal, Dan Rujescu, Teodor T Postolache
Smoking is highly prevalent in patients with schizophrenia and exerts a negative impact on cardiovascular mortality in these patients. Smoking has complex interactions with monoamine metabolism through the ability of cigarette smoke to suppress Type 1 T helper cell (Th1) type immunity, the immunophenotype that is implicated in phenylalanine hydroxylase (PAH) dysfunction and tryptophan (Trp) breakdown to kynurenine (Kyn) via indoleamine 2,3-dioxygenase. Nicotine also induces tyrosine hydroxylase (TH) gene expression, leading to increased synthesis of catecholamines...
2016: Frontiers in Public Health
Caroline M Forrest, Peter G E Kennedy, Jean Rodgers, R Neil Dalton, Charles Turner, L Gail Darlington, Stuart R Cobb, Trevor W Stone
To quantify the full range of tryptophan metabolites along the kynurenine pathway, a liquid chromatography - tandem mass spectrometry method was developed and used to analyse brain extracts of rodents treated with the kynurenine-3-mono-oxygenase (KMO) inhibitor Ro61-8048 during pregnancy. There were significant increases in the levels of kynurenine, kynurenic acid, anthranilic acid and 3-hydroxy-kynurenine (3-HK) in the maternal brain after 5 h but not 24 h, while the embryos exhibited high levels of kynurenine, kynurenic acid and anthranilic acid after 5 h which were maintained at 24 h post-treatment...
September 10, 2016: Neurochemistry International
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