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"kynurenine pathway"

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https://www.readbyqxmd.com/read/28320838/early-immune-regulatory-changes-in-a-primary-controlled-human-plasmodium-vivax-infection-cd1c-mdc-maturation-arrest-induction-of-the-kynurenine-pathway-and-regulatory-t-cell-activation
#1
Tonia Woodberry, Jessica R Loughland, Gabriela Minigo, Julie G Burel, Fiona H Amante, Kim A Piera, Yvette McNeil, Tsin W Yeo, Michael F Good, Denise L Doolan, Christian R Engwerda, James S McCarthy, Nicholas M Anstey
Plasmodium vivax malaria remains a major public health problem. The requirements for acquisition of protective immunity to this species are not clear. Dendritic cells (DC) are essential for immune cell priming, but also perform immune-regulatory functions, along with regulatory T cells (Treg). An important function of DC involves activation of the kynurenine pathway via indoleamine 2,3-dioxygenase (IDO). Using a controlled human experimental infection study with blood-stage P. vivax, we characterised plasmacytoid DC (pDC) and myeloid DC (mDC) subset maturation, CD4(+)CD25(+)CD127(lo) Treg activation and IDO activity...
March 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28319697/genetic-variants-of-the-kynurenine-3-monooxygenase-and-postpartum-depressive-symptoms-after-cesarean-section-in-chinese-women
#2
Sai-Ying Wang, Kai-Ming Duan, Xiao-Fang Tan, Ji-Ye Yin, Xiao-Yuan Mao, Wei Zheng, Chun-Yan Wang, Mi Yang, Cheng Peng, Hong-Hao Zhou, Zhao-Qian Liu
BACKGROUND: New conceptualizations of depression have emphasized the role of the kynurenine pathway (KP) in the pathogenesis of postpartum depressive symptoms (PDS). Kynurenine 3-monooxygenase (KMO) is a rate-limiting enzyme of the KP, where it catalyzes the conversion of kynurenine (KYN) to 3-hydroxykynurenine (3-HK). Previous work indicates that KMO is closely linked to the pathophysiology of depressive disorders. The purpose of this study is to investigate whether variations in the KMO gene affect PDS development after cesarean section...
March 10, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28314892/abnormal-kynurenine-pathway-of-tryptophan-catabolism-in-cardiovascular-diseases
#3
REVIEW
Ping Song, Tharmarajan Ramprasath, Huan Wang, Ming-Hui Zou
Kynurenine pathway (KP) is the primary path of tryptophan (Trp) catabolism in most mammalian cells. The KP generates several bioactive catabolites, such as kynurenine (Kyn), kynurenic acid (KA), 3-hydroxykynurenine (3-HK), xanthurenic acid (XA), and 3-hydroxyanthranilic acid (3-HAA). Increased catabolite concentrations in serum are associated with several cardiovascular diseases (CVD), including heart disease, atherosclerosis, and endothelial dysfunction, as well as their risk factors, including hypertension, diabetes, obesity, and aging...
March 17, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28303855/expression-and-prognostic-value-of-indoleamine-2-3-dioxygenase-in-pancreatic-cancer
#4
Tao Zhang, Xiang-Long Tan, Yong Xu, Zi-Zheng Wang, Chao-Hui Xiao, Rong Liu
BACKGROUND: Indoleamine 2,3-dioxygenase (IDO), an enzyme for tryptophan metabolism through the kynurenine pathway, exhibits an immunosuppressive effect and induces immune tolerance in tumor cells. The effects of IDO on pancreatic cancer are poorly understood. This study aimed to investigate the expression and prognostic significance of IDO in pancreatic cancer. METHODS: We evaluated the protein expression of IDO in PANC-1, CFPAC-1, and BxPC-3 cell lines with or without 48 h treatment by 500 U/ml interferon-γ (IFN-γ)...
March 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28275903/correlations-of-kynurenic-acid-3-hydroxykynurenine-sil-2r-ifn-%C3%AE-and-il-4-with-clinical-symptoms-during-acute-relapse-of-schizophrenia
#5
Kinga Szymona, Barbara Zdzisińska, Hanna Karakuła-Juchnowicz, Tomasz Kocki, Martyna Kandefer-Szerszeń, Marta Flis, Wojciech Rosa, Ewa M Urbańska
Several lines of evidence suggest that up-regulation of immune response and alterations of kynurenine pathway function are involved in pathogenesis of schizophrenia. Correlations among clinical status (using PANNS, SANS and SAPS scales) and blood levels of kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK) and levels of selected immunoactive molecules, soluble interleukin-2 receptor (sIL-2R), interferon-α (IFN-α) and IL-4 were analyzed in 51 chronic schizophrenia patients during acute relapse, after four weeks of therapy and at remission...
March 8, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28250737/kynurenine-pathway-metabolism-and-neuroinflammatory-disease
#6
REVIEW
Nady Braidy, Ross Grant
Immune-mediated activation of tryptophan (TRYP) catabolism via the kynurenine pathway (KP) is a consistent finding in all inflammatory disorders. Several studies by our group and others have examined the neurotoxic potential of neuroreactive TRYP metabolites, including quinolinic acid (QUIN) in neuroinflammatory neurological disorders, including Alzheimer's disease (AD), multiple sclerosis, amylotropic lateral sclerosis (ALS), and AIDS related dementia complex (ADC). Our current work aims to determine whether there is any benefit to the affected individuals in enhancing the catabolism of TRYP via the KP during an immune response...
January 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28238935/tryptophan-and-purine-metabolites-are-consistently-upregulated-in-the-urinary-metabolome-of-patients-diagnosed-with-gestational-diabetes-mellitus-throughout-pregnancy-a-longitudinal-metabolomics-study-of-chinese-pregnant-women-part-2
#7
Kai P Law, Ting-Li Han, Xun Mao, Hua Zhang
BACKGROUND: Gestational diabetes mellitus (GDM) is a pathological state of glucose intolerance associated with adverse pregnancy outcomes and an increased risk of developing maternal type 2 diabetes later in life. The mechanisms underlying GDM development are not fully understood. We examined the pathophysiology of GDM through comprehensive metabolic profiling of maternal urine, using participants from a longitudinal cohort of normal pregnancies and pregnancies complicated by GDM. METHODS: Based on ultra-performance liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry, an untargeted metabolomics study was performed to explore the differences in the urinary metabolome of GDM cases and healthy controls over the course of pregnancy...
February 24, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28223212/n-butilydenephthalide-exhibits-protection-against-neurotoxicity-through-regulation-of-tryptophan-2-3-dioxygenase-in-spinocerebellar-ataxia-type-3
#8
Karthyayani Rajamani, Jen-Wei Liu, Cheng-Han Wu, I-Tsang Chiang, Deng-Huwei You, Si-Yin Lin, Dean-Kuo Hsieh, Shinn-Zong Lin, Horng-Jyh Harn, Tzyy-Wen Chiou
Spinocerebellar ataxia type 3 or Machado-Joseph disease (SCA3/MJD) is characterized by the repetition of a CAG codon in the ataxin-3 gene (ATXN3), which leads to the formation of an elongated mutant ATXN3 protein that can neither be denatured nor undergo proteolysis in the normal manner. This abnormal proteolysis leads to the accumulation of cleaved fragments, which have been identified as toxic and further they act as a seed for more aggregate formation, thereby increasing toxicity in neuronal cells. To date, there have been few studies or treatment strategies that have focused on controlling toxic fragment formation...
February 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28212884/desipramine-decreases-expression-of-human-and-murine-indoleamine-2-3-dioxygenases
#9
Alexandra K Brooks, Tiffany M Janda, Marcus A Lawson, Jennifer L Rytych, Robin A Smith, Cecilia Ocampo-Solis, Robert H McCusker
Abundant evidence connects depression symptomology with immune system activation, stress and subsequently elevated levels of kynurenine. Anti-depressants, such as the tricyclic norepinephrine/serotonin reuptake inhibitor desipramine (Desip), were developed under the premise that increasing extracellular neurotransmitter level was the sole mechanism by which they alleviate depressive symptomologies. However, evidence suggests that anti-depressants have additional actions that contribute to their therapeutic potential...
February 16, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28195736/oxidative-fragmentations-and-skeletal-rearrangements-of-oxindole-derivatives
#10
Hendrik F T Klare, Alexander F G Goldberg, Douglas C Duquette, Brian M Stoltz
An oxidative sequence for the conversion of oxindoles to structurally distinct heterocyclic scaffolds and aniline derivatives is disclosed by the combination of a copper-catalyzed C-H peroxidation and subsequent base-mediated fragmentation reaction. In contrast to classic enzymatic (i.e., kynurenine pathway) and biomimetic methods (i.e., Witkop-Winterfeldt oxidation) for oxidative indole cleavage, this protocol allows for the incorporation of external nucleophiles. The new transformation displays broad functional group tolerance and is applicable to tryptophan derivatives, opening potential new avenues for postsynthetic modification of polypeptides, bioconjugation, and unnatural amino acid synthesis...
February 14, 2017: Organic Letters
https://www.readbyqxmd.com/read/28195169/untargeted-metabolomics-of-colonic-digests-reveals-kynurenine-pathway-metabolites-dityrosine-and-3-dehydroxycarnitine-as-red-versus-white-meat-discriminating-metabolites
#11
Caroline Rombouts, Lieselot Y Hemeryck, Thomas Van Hecke, Stefaan De Smet, Winnok H De Vos, Lynn Vanhaecke
Epidemiological research has demonstrated that the consumption of red meat is an important risk factor for the development of colorectal cancer (CRC), diabetes mellitus and cardiovascular diseases. However, there is no holistic insight in the (by-) products of meat digestion that may contribute to disease development. To address this hiatus, an untargeted mass spectrometry (MS)-based metabolomics approach was used to create red versus white meat associated metabolic fingerprints following in vitro colonic digestion using the fecal inocula of ten healthy volunteers...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28187857/adaptive-and-behavioral-changes-in-kynurenine-3-monooxygenase-knockout-mice-relevance-to-psychotic-disorders
#12
Sophie Erhardt, Ana Pocivavsek, Mariaelena Repici, Xi-Cong Liu, Sophie Imbeault, Daniel C Maddison, Marian A R Thomas, Joshua L Smalley, Markus K Larsson, Paul J Muchowski, Flaviano Giorgini, Robert Schwarcz
BACKGROUND: Kynurenine 3-monooxygenase converts kynurenine to 3-hydroxykynurenine, and its inhibition shunts the kynurenine pathway-which is implicated as dysfunctional in various psychiatric disorders-toward enhanced synthesis of kynurenic acid, an antagonist of both α7 nicotinic acetylcholine and N-methyl-D-aspartate receptors. Possibly as a result of reduced kynurenine 3-monooxygenase activity, elevated central nervous system levels of kynurenic acid have been found in patients with psychotic disorders, including schizophrenia...
December 16, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/28179491/increases-in-plasma-tryptophan-are-inversely-associated-with-incident-cardiovascular-disease-in-the-prevenci%C3%A3-n-con-dieta-mediterr%C3%A3-nea-predimed-study
#13
Edward Yu, Miguel Ruiz-Canela, Marta Guasch-Ferré, Yan Zheng, Estefania Toledo, Clary B Clish, Jordi Salas-Salvadó, Liming Liang, Dong D Wang, Dolores Corella, Montse Fitó, Enrique Gómez-Gracia, José Lapetra, Ramón Estruch, Emilio Ros, Montserrat Cofán, Fernando Arós, Dora Romaguera, Lluis Serra-Majem, Jose V Sorlí, Frank B Hu, Miguel A Martinez-Gonzalez
Background: During development of cardiovascular disease (CVD), interferon-γ-mediated inflammation accelerates degradation of tryptophan into downstream metabolites. A Mediterranean diet (MedDiet) consisting of a high intake of extra-virgin olive oil (EVOO), nuts, fruits, vegetables, and cereals has been demonstrated to lower the risk of CVD. The longitudinal relation between tryptophan and its downstream metabolites and CVD in the context of a MedDiet is unstudied.Objective: We sought to investigate the relation between metabolites in the tryptophan-kynurenine pathway and CVD in the context of a MedDiet pattern...
February 8, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28165296/the-activation-of-the-kynurenine-pathway-in-a-rat-model-with-renovascular-hypertension
#14
Jacek Bartosiewicz, Tomasz Kaminski, Krystyna Pawlak, Malgorzata Karbowska, Anna Tankiewicz-Kwedlo, Dariusz Pawlak
Hypertension is a serious condition that can lead to many health problems. The mechanisms underlying this process are still not fully understood. The kynurenine pathway may be involved in the occurrence and progression of hypertension. The purpose of this study was to examine the activity of peripheral kynurenine pathway in rats with renovascular hypertension in Goldblatt 2K1C model. Hypertension was induced in the experimental groups by constricting the renal artery of the left kidney of the rats. Determination of tryptophan (Trp) and kynurenine pathway metabolites was assessed by high-performance liquid chromatography in plasma and tissues obtained at 4, 8, and 16 weeks after the surgical intervention or sham surgery...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28159919/evaluation-of-radiofluorinated-carboximidamides-as-potential-ido-targeted-pet-tracers-for-cancer-imaging
#15
Xuan Huang, Zhongjie Pan, Michael L Doligalski, Xia Xiao, Epifanio Ruiz, Mikalai M Budzevich, Haibin Tian
IDO1 is an enzyme catalyzing the initial and rate-limiting step in the catabolism of tryptophan along the kynurenine pathway. IDO1 expression could suppress immune responses by blocking T-lymphocyte proliferation locally, suggesting a role of IDO in the regulation of immune responses. The goal of this study was to evaluate the potential of radiofluorinated carboximidamides as selective PET radioligands for IDO1. Specific binding correlated with IDO1 expression as measured through in vitro, microPET experiments...
January 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28155867/kynurenine-pathway-metabolomics-predicts-and-provides-mechanistic-insight-into-multiple-sclerosis-progression
#16
Chai K Lim, Ayse Bilgin, David B Lovejoy, Vanessa Tan, Sonia Bustamante, Bruce V Taylor, Alban Bessede, Bruce J Brew, Gilles J Guillemin
Activation of the kynurenine pathway (KP) of tryptophan metabolism results from chronic inflammation and is known to exacerbate progression of neurodegenerative disease. To gain insights into the links between inflammation, the KP and multiple sclerosis (MS) pathogenesis, we investigated the KP metabolomics profile of MS patients. Most significantly, we found aberrant levels of two key KP metabolites, kynurenic acid (KA) and quinolinic acid (QA). The balance between these metabolites is important as it determines overall excitotoxic activity at the N-methyl-D-Aspartate (NMDA) receptor...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28155213/intracerebroventricular-administration-of-streptozotocin-as-an-experimental-approach-to-depression-evidence-for-the-involvement-of-proinflammatory-cytokines-and-indoleamine-2-3-dioxygenase
#17
Leandro Cattelan Souza, Cristiano R Jesse, Marcelo Gomes de Gomes, Cristini Escobar Viana, Etiara Mattos, Neici Cáceres Silva, Silvana Peterini Boeira
There is a lack of information about the molecular events underlying the depressive-like effect of an intracerebroventricular injection of streptozotocin (ICV-STZ) in mice. Elevated activity of the tryptophan-degrading enzyme indoleamine-2,3-dioxygenase (IDO) has been proposed to mediate depression in inflammatory disorders. In this study, we report that ICV-STZ activates IDO in the hippocampus of mice and culminates in depressive-like behaviors, measured by an increased duration in immobility time in the forced swimming test and decreased total time of grooming in the splash test...
February 2, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28113063/5-hydroxytryptophan-a-major-product-of-tryptophan-degradation-is-essential-for-optimal-replication-of-human-parainfluenza-virus
#18
M A G Rabbani, Sailen Barik
Interferon (IFN) exerts its antiviral effect by inducing a large family of cellular genes, named interferon (IFN)-stimulated genes (ISGs). An intriguing member of this family is indoleamine 2,3-dioxygenase (IDO), which catalyzes the first and rate-limiting step of the main branch of tryptophan (Trp) degradation, the kynurenine pathway. We recently showed that IDO strongly inhibits human parainfluenza virus type 3 (PIV3), a significant respiratory pathogen. Here, we show that 5-hydoxytryptophan (5-HTP), the first product of an alternative branch of Trp degradation and a serotonin precursor, is essential to protect virus growth against IDO in cell culture...
March 2017: Virology
https://www.readbyqxmd.com/read/28112061/inflammation-and-depression-a-causal-or-coincidental-link-to-the-pathophysiology
#19
Brian E Leonard
This review summarises the evidence that chronic low grade inflammation triggers changes that contribute to the mental and physical ill health of patients with major depression. Inflammation, and the activation of the hypothalamic pituitary axis by stress, are normal components of the stress response but when stress is prolonged and the endocrine and immune system become chronic resulting in the activation of the peripheral macrophages, the central microglia and hypercortisolemia, the neuronal networks are damaged and become dysfunctional...
January 23, 2017: Acta Neuropsychiatrica
https://www.readbyqxmd.com/read/28078987/role-of-proinflammatory-cytokines-in-dopaminergic-system-disturbances-implications-for-anhedonic-features-of-mdd
#20
Zihang Pan, Joshua D Rosenblat, Walter Swardfager, Roger S McIntyre
Anhedonia, characterized by a loss of interest and/or pleasure in previously enjoyable activities, is an important diagnostic criterion of Major Depressive Disorder (MDD). Converging evidence implicates a behaviouralcausal relationship between proinflammatory cytokines and disturbances that characterize anhedonia in the context of MDD. Additionally, anhedonia has been implicated in disturbances of key central dopaminergic modulatory pathways. Emerging research into the roles of tetrahydrobiopterin, a cytokine-targeted co-enzyme in the synthesis of dopamine, and kynurenine, a product of inflammation-sensitive breakdown of tryptophan via indoleamine 2, 3-dioxygenase, have shed new light into the role of inflammation in mediating anhedonic behaviours...
January 11, 2017: Current Pharmaceutical Design
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