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Kui Jiao - One of the best experts on this subject based on the ideXlab platform.
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a reductively treated thin layer mos2 nanosheet poly Xanthurenic Acid composite with dramatically enhanced electrochemical performance and extended sensing applications
Electrochimica Acta, 2016Co-Authors: Xinxing Wang, Tao Yang, Kui JiaoAbstract:Abstract Polymer inorganic nanosheet composites hold great promise in electrochemical sensing applications by improving the electrochemical performance and increasing the surface area. In this work, a reductively treated thin layer molybdenum disulfide nanosheet-poly(Xanthurenic Acid) (rTLMoS2-PXa) composite have been facilely prepared through a one-step electrosynthesis procedure. The TLMoS2 was used as building block for the construction of the composite with the PXa coated on it. The composite modified electrode possesses improved electron transfer capability and exhibits good electrochemical sensing performance towards several heterocyclic and aromatic ring compounds (2′-deoxyguanosine-5′-triphosphate trisodium salt, dGTP, bisphenol A, BPA and 2,4,6-trinitrotoluene, TNT), which have good affinity to the electroactive PXa and never or rarely been analyzed by MoS2-based sensing platform. This research provides a new electrochemical sensing platform for simple and sensitive detection of dGTP, BPA and TNT, and further extends the application of MoS2 in the field of electrochemical sensing.
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enhanced electropolymerization of poly Xanthurenic Acid mos2 film for specific electrocatalytic detection of guanine and adenine
Journal of Materials Chemistry B, 2015Co-Authors: Tao Yang, Lihua Chen, Meijing Chen, Fuxin Nan, Xiliang Luo, Kui JiaoAbstract:Until now, research studies on the preparation of MoS2-based polymer nanocomposites using the electropolymerization method have been scarce. Herein, for the first time, a poly(Xanthurenic Acid, Xa) film based on a thin-layer MoS2 support was electrochemically prepared to form a highly electroactive biosensing platform. The thin-layer MoS2 was obtained using a simple ultrasonic method from bulk MoS2. The physical adsorption between MoS2 and aromatic Xa improved the electropolymerization efficiency, accompanied by an increased electrochemical response of PXa. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), cyclic voltammetry (CV), and differential pulse voltammetry (DPV) were utilized to characterize the morphology and investigate the electrochemical properties of the prepared interface. Compared with sole PXa or a MoS2 modified electrode, the PXa-MoS2 hybrid interface exhibited good electrocatalytic activity and prominent synergistic effect on guanine and adenine. A PXa-MoS2 nanocomposite has the negative charge and a specific structure, which obviously prompts the adsorption of the positively charged guanine and adenine. Moreover, this nanocomposite is a promising candidate in electrochemical sensing and other electrocatalytic applications.
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highly sensitive and synergistic detection of guanine and adenine based on poly Xanthurenic Acid reduced graphene oxide interface
ACS Applied Materials & Interfaces, 2014Co-Authors: Tao Yang, Qianqian Kong, Xinxing Wang, Lihua Chen, Kui JiaoAbstract:In order to achieve the large direct electrochemical signals of guanine and adenine, an urgent request to explore novel electrode materials and interfaces has been put forward. In this paper, a poly(Xanthurenic Acid, Xa)-reduced graphene oxide (PXa-ERGNO) interface, which has rich negatively charged active sites and accelerated electron transfer ability, was fabricated for monitoring the positively charged guanine and adenine. Scanning electron microscopy, Fourier transform infrared spectroscopy, Raman spectra, X-ray photoelectron spectroscopy, cyclic voltammetry, electrochemical impedance spectroscopy, and differential pulse voltammetry were adopted to characterize the morphology and prove the electrochemical properties of the prepared interface. The PXa-ERGNO interface with rich negative charge and large electrode surface area was an excellent sensing platform to prompt the adsorption of the positively charged guanine and adenine via strong π–π* interaction or electrostatic adsorption. The PXa-ERGNO int...
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one step electropolymerization of Xanthurenic Acid graphene film prepared by a pulse potentiostatic method for simultaneous detection of guanine and adenine
Polymer Chemistry, 2014Co-Authors: Tao Yang, Qianqian Kong, Xinxing Wang, Lihua Chen, Kui JiaoAbstract:A novel one-step electrochemical synthesis via a pulse potentiostatic method (PPM) was adopted to prepare a nanocomposite of poly(Xanthurenic Acid, Xa)–electrochemically reduced graphene oxide (PXa–ERGNO), which was applied for simultaneous detection of guanine and adenine. In the synthesis process, the graphene oxide (GNO) could be electrochemically reduced to reduced graphene oxide in the cathodic potential section; meanwhile, Xa (an unconventional and low toxicity biomonomer) could be electropolymerized in the anodic potential section. The optimization of fabrication was based on the electrooxidation signals of DNA bases. Since the negative charge and specific structure of the nanocomposite can prompt the adsorption of the electropositive guanine and adenine via strong π–π* interactions or electrostatic adsorption, the resulting nanocomposite shows high electrocatalytic ability for the detection of guanine and adenine.
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synchronous electrosynthesis of poly Xanthurenic Acid reduced graphene oxide nanocomposite for highly sensitive impedimetric detection of dna
ACS Applied Materials & Interfaces, 2013Co-Authors: Tao Yang, Le Meng, Xiaohong Wang, Wenwen Chen, Kui JiaoAbstract:A novel and simple synchronous electrochemical synthesis of poly(Xanthurenic Acid, Xa), electrochemically reduced graphene oxide nanocomposite (PXa-ERGNO), via cyclic voltammetry (CV) was reported, where graphene oxide (GNO) and Xa monomer were adopted as precursors. The resulting PXa-ERGNO nanocomposite was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, CV and electrochemical impedance spectroscopy (EIS). The π–π* interactions between the conjugated GNO layers and aromatic ring of Xa-enhanced the electropolymerization efficiency accompanied with an increased electrochemical response of PXa. The rich carboxyl groups of PXa-ERGNO film were applied to stably immobilize the probe DNA with amino groups at 5′ end via covalent bonding. The captured probe could sensitively and selectively recognize its target DNA via EIS. The dynamic detection range was from 1.0 × 10–14 mol/L to 1.0 × 10–8 mol/L with a detection limit of 4.2 × 10–15 mol/L due to the synergistic effect of ...
T E Salt - One of the best experts on this subject based on the ideXlab platform.
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Xanthurenic Acid formation from 3 hydroxykynurenine in the mammalian brain neurochemical characterization and physiological effects
Neuroscience, 2017Co-Authors: Korrapati V Sathyasaikumar, S A Neale, T E Salt, Margarita Tararina, F Weisz, Robert SchwarczAbstract:Xanthurenic Acid (XA), formed from 3-hydroxykynurenine (3-HK) in the kynurenine pathway of tryptophan degradation, may modulate glutamatergic neurotransmission by inhibiting the vesicular glutamate transporter and/or activating Group II metabotropic glutamate receptors. Here we examined the molecular and cellular mechanisms by which 3-HK controls the neosynthesis of XA in rat, mouse and human brain, and compared the physiological actions of 3-HK and XA in the rat brain. In tissue homogenates, XA formation from 3-HK was observed in all three species and traced to a major role of kynurenine aminotransferase II (KAT II). Transamination of 3-HK to XA was also demonstrated using human recombinant KAT II. Neosynthesis of XA was significantly increased in the quinolinate-lesioned rat striatum, indicating a non-neuronal localization of the process. Studies using rat cortical slices revealed that newly produced XA is rapidly released into the extracellular compartment, and that XA biosynthesis can be manipulated experimentally in the same way as the production of kynurenic Acid from kynurenine (omission of Na+ or glucose, depolarizing conditions, or addition of 2-oxoAcids). The synthesis of XA from 3-HK was confirmed in vivo by striatal microdialysis. In slices from the rat hippocampus, both 3-HK and XA reduced the slopes of dentate gyrus field EPSPs. The effect of 3-HK was reduced in the presence of the KAT inhibitor aminooxyacetic Acid. Finally, both 3-HK and XA reduced the power of gamma-oscillatory activity recorded from the hippocampal CA3 region. Endogenous XA, newly formed from 3-HK, may therefore play a physiological role in attentional and cognitive processes.
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Cinnabarinic Acid and Xanthurenic Acid: Two kynurenine metabolites that interact with metabotropic glutamate receptors
PERGAMON-ELSEVIER SCIENCE LTD, 2017Co-Authors: Fazio F, S A Neale, T E Salt, Lionetto L, Curto M, Iacovelli L, Cs Copeland, Battaglia G, Nicoletti FAbstract:Cinnabarinic and Xanthurenic Acids are kynurenine metabolites generated by oxidative dimerization of 3-hydroxyanthranilic Acid and transamination of 3-hydroxykynurenine, respectively. Recent evidence suggests that both compounds can affect brain function and neurotransmission and interact with metabotropic glutamate (mGlu) receptors. Cinnabarinic Acid behaves as an orthosteric agonist of mGlu4 receptors, whereas some of the in vitro and in vivo effects produced by Xanthurenic Acid appear to be mediated by the activation of mGlu2 and mGlu3 receptors. Cinnabarinic Acid could play an important role in mechanisms of neuroinflammation acting as a linking bridge between the immune system and the CNS. Xanthurenic Acid has potential implications in the pathophysiology of schizophrenia and is a promising candidate as a peripheral biomarker of the disorder. The action of cinnabarinic Acid and Xanthurenic Acid may extend beyond the regulation of mGlu receptors and may involve several diverse molecular targets, such as the aryl hydrocarbon receptor for cinnabarinic Acid and vesicular glutamate transporters for Xanthurenic Acid. The growing interest on these two metabolites of the kynurenine pathway may unravel new aspects in the complex interaction between tryptophan metabolism and brain function, and lead to the discovery of new potential targets for the treatment of neurological and psychiatric disorders
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cinnabarinic Acid and Xanthurenic Acid two kynurenine metabolites that interact with metabotropic glutamate receptors
Neuropharmacology, 2017Co-Authors: Francesco Fazio, Caroline S Copeland, S A Neale, T E Salt, Luana Lionetto, Giuseppe Battaglia, Valeria Bruno, Martina Curto, Luisa Iacovelli, Ferdinando NicolettiAbstract:Abstract Cinnabarinic and Xanthurenic Acids are kynurenine metabolites generated by oxidative dimerization of 3-hydroxyanthranilic Acid and transamination of 3-hydroxykynurenine, respectively. Recent evidence suggests that both compounds can affect brain function and neurotransmission and interact with metabotropic glutamate (mGlu) receptors. Cinnabarinic Acid behaves as an orthosteric agonist of mGlu4 receptors, whereas some of the in vitro and in vivo effects produced by Xanthurenic Acid appear to be mediated by the activation of mGlu2 and mGlu3 receptors. Cinnabarinic Acid could play an important role in mechanisms of neuroinflammation acting as a linking bridge between the immune system and the CNS. Xanthurenic Acid has potential implications in the pathophysiology of schizophrenia and is a promising candidate as a peripheral biomarker of the disorder. The action of cinnabarinic Acid and Xanthurenic Acid may extend beyond the regulation of mGlu receptors and may involve several diverse molecular targets, such as the aryl hydrocarbon receptor for cinnabarinic Acid and vesicular glutamate transporters for Xanthurenic Acid. The growing interest on these two metabolites of the kynurenine pathway may unravel new aspects in the complex interaction between tryptophan metabolism and brain function, and lead to the discovery of new potential targets for the treatment of neurological and psychiatric disorders. This article is part of the Special Issue entitled ‘The Kynurenine Pathway in Health and Disease’.
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actions of Xanthurenic Acid a putative endogenous group ii metabotropic glutamate receptor agonist on sensory transmission in the thalamus
Neuropharmacology, 2013Co-Authors: Caroline S Copeland, S A Neale, T E SaltAbstract:Abstract Xanthurenic Acid (XA), a molecule arising from tryptophan metabolism by transamination of 3-hydroxykynurenine, has recently been identified as an endogenous Group II (mGlu2 and mGlu3) metabotropic glutamate (mGlu) receptor ligand in vitro. Impairments in Group II mGlu receptor expression and function have been implicated in the pathophysiology of schizophrenia, as have multiple steps in the kynurenine metabolism pathway. Therefore, we examined XA in vivo to further investigate its potential as a Group II mGlu receptor ligand using a preparation that has been previously demonstrated to efficiently reveal the action of other Group II mGlu receptor ligands in vivo. Extracellular single-neurone recordings were made in the rat ventrobasal thalamus (VB) in conjunction with iontophoresis of agonists, an antagonist and a positive allosteric modulator and/or intravenous (i.v.) injection of XA. We found the XA effect on sensory inhibition, when applied iontophoretically and i.v., was similar to that of other Group II mGlu receptor agonists in reducing inhibition evoked in the VB from the thalamic reticular nucleus upon physiological sensory stimulation. Furthermore, we postulate that XA may be the first potential endogenous allosteric agonist (termed ‘endocoid’) for the mGlu receptors. As the Group II receptors and kynurenine metabolism pathway have both been heavily implicated in the pathophysiology of schizophrenia, XA could play a pivotal role in antipsychotic research as this potential endocoid represents both a convergence within these two biological parameters and a novel class of Group II mGlu receptor ligand. This article is part of a Special Issue entitled ‘Metabotropic Glutamate Receptors’.
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modulation of hippocampal synaptic transmission by the kynurenine pathway member Xanthurenic Acid and other vglut inhibitors
Neuropsychopharmacology, 2013Co-Authors: S A Neale, Caroline S Copeland, Victor N Uebele, Fiona Thomson, T E SaltAbstract:Xanthurenic Acid (XA), an endogenous kynurenine, is a known vesicular glutamate transport (VGLUT) inhibitor and has also been proposed as an mGlu2/3 receptor agonist. Changes in these systems have been implicated in the pathophysiology of schizophrenia and other psychiatric disorders; however, little is known of how XA affects synaptic transmission. We therefore investigated the effects of XA on synaptic transmission at two hippocampal glutamatergic pathways and evaluated the ability of XA to bind to mGlu2/3 receptors. Field excitatory postsynaptic potentials (fEPSPs) were recorded from either the dentate gyrus (DG) or CA1 region of mouse hippocampal slices in vitro. Addition of XA to the bathing medium (1–10 mM) resulted in a dose-related reduction of fEPSP amplitudes (up to 52% reduction) in both hippocampal regions. In the DG, the VGLUT inhibitors Congo Red and Rose Bengal, and the mGlu2/3 agonist LY354740, also reduced fEPSPs (up to 80% reduction). The mGlu2/3 antagonist LY341495 reversed the LY354740 effect, but not the XA effect. LY354740, but not XA, also reduced DG paired-pulse depression. XA had no effect on specific binding of 1 nM [3H]LY341495 to membranes with human mGlu2 receptors. We conclude that XA can modulate synaptic transmission via a mechanism that may involve VGLUT inhibition rather than activation of mGlu2/3 receptors. This could be important in the pathophysiology of nervous system disorders including schizophrenia and might represent a target for developing novel pharmacological therapies.
Wei Zhang - One of the best experts on this subject based on the ideXlab platform.
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tungsten disulfide nanosheets supported poly Xanthurenic Acid as a signal transduction interface for electrochemical genosensing applications
RSC Advances, 2018Co-Authors: Jimin Yang, Xuesong Yin, Min Xia, Wei ZhangAbstract:Tungsten disulfide (WS2) nanosheets supported poly(Xanthurenic Acid) (PXa) was used as the signal transduction interface for electrochemical genosensing. The WS2 nanosheets were obtained from bulk WS2 using a simple ultrasonic method. Due to the unique physical adsorption of Xa monomers to WS2, the electropolymerization efficiency was greatly improved, accompanied with an increased electrochemical response of PXa. The obtained PXa/WS2 nanocomposite not only served as a substrate for DNA immobilization but also reflected the electrochemical transduction originating from DNA immobilization and hybridization without any other indicators or complicated labelling steps. Owing to the presence of abundant carboxyl groups, the probe ssDNA was covalently attached on the carboxyl-terminated PXa/WS2 nanocomposite through the free amines of DNA sequences based on the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydrosulfosuccinimide crosslinking reaction. The covalently immobilized probe ssDNA could selectively hybridize with its target DNA to form dsDNA on the surface of the PXa/WS2 nanocomposite. This developed biosensor achieved a satisfactory detection limit down to 1.6 × 10−16 mol L−1 and a dynamic range of 1.0 × 10−15 to 1.0 × 10−11 mol L−1 for detection of circulating tumor DNA related to gastric carcinoma. Selectivity of the biosensor has been investigated in presence of non-complementary, one-mismatched and two-mismatched DNA sequences.
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high performance electrochemical sensing of circulating tumor dna in peripheral blood based on poly Xanthurenic Acid functionalized mos2 nanosheets
Biosensors and Bioelectronics, 2018Co-Authors: Wei Zhang, Zhichao Dai, Xue Liu, Jimin YangAbstract:A high-performance sensing platform based on poly-Xanthurenic Acid (PXA) film functionalized MoS2 nanosheets was developed for electrochemical detection of circulating tumor DNA in peripheral blood. The MoS2 nanosheets were obtained using a simple ultrasonic method from bulk MoS2. The physical adsorption between MoS2 and aromatic XA monomers effectively improved the electropolymerization efficiency, accompanied with an increased electrochemical response of PXA. The obtained PXA/MoS2 nanocomposite not only served as a substrate for DNA immobilization but also reflected the electrochemical transduction originating from DNA immobilization and hybridization without any complex labelling processes or outer indicators. The immobilization of the probe ssDNA was achieved via noncovalent assembly due to the π-π interaction between PXA and DNA bases. After the hybridization of the probe ssDNA with the target DNA, the formation of helix structure induced the resulted dsDNA to be released from the surface of the PXA/MoS2 nanocomposite. The detection limit of this constructed DNA biosensor was calculated in the linear target DNA concentrations range from 1.0 × 10-16 mol/L to 1.0 × 10-10 mol/L and it was found to be 1.8 × 10-17 mol/L.
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development of dna monitoring platform based on poly Xanthurenic Acid functionalized fept reduced graphene oxide
Journal of Solid State Electrochemistry, 2015Co-Authors: Wei ZhangAbstract:A freely switchable DNA monitoring platform based on poly(Xanthurenic Acid) functionalized FePt/reduced graphene oxide (PXa-FePt/RGO) was developed, where the PXa and FePt/RGO were synchronously synthesized via an effective pulse potentiostatic method. The obtained nanocomposite integrated the advantages of the PXa and FePt/RGO, including rich-conjugated structures, good conductivity, and fine biocompatibility, which not only served as a substrate for DNA immobilization but also reflected the electrochemical transduction originating from DNA immobilization and hybridization without any complicated labeling or outer indicators. The immobilization of probe DNA was successfully conducted via noncovalent assembly due to the π–π* interaction between the conjugated nanocomposite and DNA bases. After the hybridization of probe DNA with target DNA, the formation of double-helix structure induced dsDNA to release from the surface of conjugated nanocomposite, accompanied with the self-signal regeneration of nanocomposite (“signal-on”). The developed biosensor exhibited excellent performance for the detection of the sequence-specific DNA from chronic myelogenous leukemia by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) with a detection limit of 2.1 × 10−16 mol/L.
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indicator free electrochemical genosensing originated from the self signal of poly Xanthurenic Acid enhanced by fe3o4 reduced graphene oxide
Journal of Solid State Electrochemistry, 2014Co-Authors: Wei Zhang, Libin Wang, Xiuwen ZhengAbstract:In this paper, an indicator-free electrochemical genosensing platform based on the self-signal changes of poly-Xanthurenic Acid (PXa) enhanced by Fe3O4/reduced graphene oxide (Fe3O4/RGO) was constructed. The resulting nanocomposite (PXa-Fe3O4/RGO) was characterized by transmission electron microscopy, cyclic voltammetry, and electrochemical impedance spectroscopy (EIS). The π–π* stacking and hydrogen bonding between the conjugated Fe3O4/GO and aromatic ring of Xanthurenic Acid monomer promoted the electropolymerization efficiency accompanied with an increased electrochemical response of PXa. The immobilization of the specific probe DNA was successfully realized via the noncovalent method due to the π–π* interaction between the conjugated nanostructure of PXa-Fe3O4/RGO and DNA bases. The hybridization between the probe DNA and target DNA induced the resulted double-stranded (ds)DNA to be released from the conjugated nanocomposite, accompanied with the self-signal regeneration of nanocomposite (“signal-on”). The self-signal changes could serve as a powerful tool for indicator-free and freely switchable detection of different target genes, and the synergistic effect of the integrated graphene-based nanocomposite effectively improved the sensitivity for the target DNA detection via EIS.
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biocompatible nanostructured poly Xanthurenic Acid fe2o3 reduced graphene oxide platform for genosensing application
Journal of Electroanalytical Chemistry, 2014Co-Authors: Wei Zhang, Xiuwen ZhengAbstract:Abstract A biocompatible nanostructured poly(Xanthurenic Acid)–Fe2O3/reduced graphene oxide (PXa–Fe2O3/RGO) platform was constructed for electrochemical sensing of DNA hybridization. The affinity of nanosized Fe2O3 with Xanthurenic Acid (Xa) monomer coupled with the π–π* stacking and hydrogen bonding between the conjugated graphene oxide layers and aromatic ring of Xa enhanced the electropolymerization efficient, resulting in an improved electrochemical response of PXa. The obtained PXa–Fe2O3/RGO nanocomposite integrated the advantages of the Fe2O3/RGO and PXa, owning rich-conjugated structures, fine biocompatibility, and good conductivity. The immobilization of the probe DNA was successfully achieved via noncovalent bonding due to π–π* interaction between the conjugated PXa–Fe2O3/RGO and DNA bases. After the hybridization of probe DNA with target DNA, the formation of double-helix structure induced dsDNA to release from the surface of conjugated nanocomposite, accompanied with the self-signal regeneration of nanocomposite (“signal-on”). The self-signal changes induced by DNA immobilization and hybridization could be sensitively recognized via cyclic voltammetry and electrochemical impedance spectroscopy, and the synergistic effect of the graphene-based nanocomposite improved the sensitivity for the target DNA detection.
S A Neale - One of the best experts on this subject based on the ideXlab platform.
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Xanthurenic Acid formation from 3 hydroxykynurenine in the mammalian brain neurochemical characterization and physiological effects
Neuroscience, 2017Co-Authors: Korrapati V Sathyasaikumar, S A Neale, T E Salt, Margarita Tararina, F Weisz, Robert SchwarczAbstract:Xanthurenic Acid (XA), formed from 3-hydroxykynurenine (3-HK) in the kynurenine pathway of tryptophan degradation, may modulate glutamatergic neurotransmission by inhibiting the vesicular glutamate transporter and/or activating Group II metabotropic glutamate receptors. Here we examined the molecular and cellular mechanisms by which 3-HK controls the neosynthesis of XA in rat, mouse and human brain, and compared the physiological actions of 3-HK and XA in the rat brain. In tissue homogenates, XA formation from 3-HK was observed in all three species and traced to a major role of kynurenine aminotransferase II (KAT II). Transamination of 3-HK to XA was also demonstrated using human recombinant KAT II. Neosynthesis of XA was significantly increased in the quinolinate-lesioned rat striatum, indicating a non-neuronal localization of the process. Studies using rat cortical slices revealed that newly produced XA is rapidly released into the extracellular compartment, and that XA biosynthesis can be manipulated experimentally in the same way as the production of kynurenic Acid from kynurenine (omission of Na+ or glucose, depolarizing conditions, or addition of 2-oxoAcids). The synthesis of XA from 3-HK was confirmed in vivo by striatal microdialysis. In slices from the rat hippocampus, both 3-HK and XA reduced the slopes of dentate gyrus field EPSPs. The effect of 3-HK was reduced in the presence of the KAT inhibitor aminooxyacetic Acid. Finally, both 3-HK and XA reduced the power of gamma-oscillatory activity recorded from the hippocampal CA3 region. Endogenous XA, newly formed from 3-HK, may therefore play a physiological role in attentional and cognitive processes.
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Cinnabarinic Acid and Xanthurenic Acid: Two kynurenine metabolites that interact with metabotropic glutamate receptors
PERGAMON-ELSEVIER SCIENCE LTD, 2017Co-Authors: Fazio F, S A Neale, T E Salt, Lionetto L, Curto M, Iacovelli L, Cs Copeland, Battaglia G, Nicoletti FAbstract:Cinnabarinic and Xanthurenic Acids are kynurenine metabolites generated by oxidative dimerization of 3-hydroxyanthranilic Acid and transamination of 3-hydroxykynurenine, respectively. Recent evidence suggests that both compounds can affect brain function and neurotransmission and interact with metabotropic glutamate (mGlu) receptors. Cinnabarinic Acid behaves as an orthosteric agonist of mGlu4 receptors, whereas some of the in vitro and in vivo effects produced by Xanthurenic Acid appear to be mediated by the activation of mGlu2 and mGlu3 receptors. Cinnabarinic Acid could play an important role in mechanisms of neuroinflammation acting as a linking bridge between the immune system and the CNS. Xanthurenic Acid has potential implications in the pathophysiology of schizophrenia and is a promising candidate as a peripheral biomarker of the disorder. The action of cinnabarinic Acid and Xanthurenic Acid may extend beyond the regulation of mGlu receptors and may involve several diverse molecular targets, such as the aryl hydrocarbon receptor for cinnabarinic Acid and vesicular glutamate transporters for Xanthurenic Acid. The growing interest on these two metabolites of the kynurenine pathway may unravel new aspects in the complex interaction between tryptophan metabolism and brain function, and lead to the discovery of new potential targets for the treatment of neurological and psychiatric disorders
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cinnabarinic Acid and Xanthurenic Acid two kynurenine metabolites that interact with metabotropic glutamate receptors
Neuropharmacology, 2017Co-Authors: Francesco Fazio, Caroline S Copeland, S A Neale, T E Salt, Luana Lionetto, Giuseppe Battaglia, Valeria Bruno, Martina Curto, Luisa Iacovelli, Ferdinando NicolettiAbstract:Abstract Cinnabarinic and Xanthurenic Acids are kynurenine metabolites generated by oxidative dimerization of 3-hydroxyanthranilic Acid and transamination of 3-hydroxykynurenine, respectively. Recent evidence suggests that both compounds can affect brain function and neurotransmission and interact with metabotropic glutamate (mGlu) receptors. Cinnabarinic Acid behaves as an orthosteric agonist of mGlu4 receptors, whereas some of the in vitro and in vivo effects produced by Xanthurenic Acid appear to be mediated by the activation of mGlu2 and mGlu3 receptors. Cinnabarinic Acid could play an important role in mechanisms of neuroinflammation acting as a linking bridge between the immune system and the CNS. Xanthurenic Acid has potential implications in the pathophysiology of schizophrenia and is a promising candidate as a peripheral biomarker of the disorder. The action of cinnabarinic Acid and Xanthurenic Acid may extend beyond the regulation of mGlu receptors and may involve several diverse molecular targets, such as the aryl hydrocarbon receptor for cinnabarinic Acid and vesicular glutamate transporters for Xanthurenic Acid. The growing interest on these two metabolites of the kynurenine pathway may unravel new aspects in the complex interaction between tryptophan metabolism and brain function, and lead to the discovery of new potential targets for the treatment of neurological and psychiatric disorders. This article is part of the Special Issue entitled ‘The Kynurenine Pathway in Health and Disease’.
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actions of Xanthurenic Acid a putative endogenous group ii metabotropic glutamate receptor agonist on sensory transmission in the thalamus
Neuropharmacology, 2013Co-Authors: Caroline S Copeland, S A Neale, T E SaltAbstract:Abstract Xanthurenic Acid (XA), a molecule arising from tryptophan metabolism by transamination of 3-hydroxykynurenine, has recently been identified as an endogenous Group II (mGlu2 and mGlu3) metabotropic glutamate (mGlu) receptor ligand in vitro. Impairments in Group II mGlu receptor expression and function have been implicated in the pathophysiology of schizophrenia, as have multiple steps in the kynurenine metabolism pathway. Therefore, we examined XA in vivo to further investigate its potential as a Group II mGlu receptor ligand using a preparation that has been previously demonstrated to efficiently reveal the action of other Group II mGlu receptor ligands in vivo. Extracellular single-neurone recordings were made in the rat ventrobasal thalamus (VB) in conjunction with iontophoresis of agonists, an antagonist and a positive allosteric modulator and/or intravenous (i.v.) injection of XA. We found the XA effect on sensory inhibition, when applied iontophoretically and i.v., was similar to that of other Group II mGlu receptor agonists in reducing inhibition evoked in the VB from the thalamic reticular nucleus upon physiological sensory stimulation. Furthermore, we postulate that XA may be the first potential endogenous allosteric agonist (termed ‘endocoid’) for the mGlu receptors. As the Group II receptors and kynurenine metabolism pathway have both been heavily implicated in the pathophysiology of schizophrenia, XA could play a pivotal role in antipsychotic research as this potential endocoid represents both a convergence within these two biological parameters and a novel class of Group II mGlu receptor ligand. This article is part of a Special Issue entitled ‘Metabotropic Glutamate Receptors’.
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modulation of hippocampal synaptic transmission by the kynurenine pathway member Xanthurenic Acid and other vglut inhibitors
Neuropsychopharmacology, 2013Co-Authors: S A Neale, Caroline S Copeland, Victor N Uebele, Fiona Thomson, T E SaltAbstract:Xanthurenic Acid (XA), an endogenous kynurenine, is a known vesicular glutamate transport (VGLUT) inhibitor and has also been proposed as an mGlu2/3 receptor agonist. Changes in these systems have been implicated in the pathophysiology of schizophrenia and other psychiatric disorders; however, little is known of how XA affects synaptic transmission. We therefore investigated the effects of XA on synaptic transmission at two hippocampal glutamatergic pathways and evaluated the ability of XA to bind to mGlu2/3 receptors. Field excitatory postsynaptic potentials (fEPSPs) were recorded from either the dentate gyrus (DG) or CA1 region of mouse hippocampal slices in vitro. Addition of XA to the bathing medium (1–10 mM) resulted in a dose-related reduction of fEPSP amplitudes (up to 52% reduction) in both hippocampal regions. In the DG, the VGLUT inhibitors Congo Red and Rose Bengal, and the mGlu2/3 agonist LY354740, also reduced fEPSPs (up to 80% reduction). The mGlu2/3 antagonist LY341495 reversed the LY354740 effect, but not the XA effect. LY354740, but not XA, also reduced DG paired-pulse depression. XA had no effect on specific binding of 1 nM [3H]LY341495 to membranes with human mGlu2 receptors. We conclude that XA can modulate synaptic transmission via a mechanism that may involve VGLUT inhibition rather than activation of mGlu2/3 receptors. This could be important in the pathophysiology of nervous system disorders including schizophrenia and might represent a target for developing novel pharmacological therapies.
Marie Favennec - One of the best experts on this subject based on the ideXlab platform.
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post bariatric surgery changes in quinolinic and Xanthurenic Acid concentrations are associated with glucose homeostasis
PLOS ONE, 2016Co-Authors: Marie Favennec, Benjamin Hennart, Marie Verbanck, M Pigeyre, Robert CaiazzoAbstract:Background An increase of plasma kynurenine concentrations, potentially bioactive metabolites of tryptophan, was found in subjects with obesity, resulting from low-grade inflammation of the white adipose tissue. Bariatric surgery decreases low-grade inflammation associated with obesity and improves glucose control. Objective Our goal was to determine the concentrations of all kynurenine metabolites after bariatric surgery and whether they were correlated with glucose control improvement. Design Kynurenine metabolite concentrations, analysed by liquid or gas chromatography coupled with tandem mass spectrometry, circulating inflammatory markers, metabolic traits, and BMI were measured before and one year after bariatric surgery in 44 normoglycemic and 47 diabetic women with obesity. Associations between changes in kynurenine metabolites concentrations and in glucose control and metabolic traits were analysed between baseline and twelve months after surgery. Results Tryptophan and kynurenine metabolite concentrations were significantly decreased one year after bariatric surgery and were correlated with the decrease of the usCRP in both groups. Among all the kynurenine metabolites evaluated, only quinolinic Acid and Xanthurenic Acid were significantly associated with glucose control improvement. The one year delta of quinolinic Acid concentrations was negatively associated with the delta of fasting glucose (p = 0.019) and HbA1c (p = 0.014), whereas the delta of Xanthurenic Acid was positively associated with the delta of insulin sensitivity index (p = 0.0018). Conclusion Bariatric surgery has induced a global down-regulation of kynurenine metabolites, associated with weight loss. Our results suggest that, since kynurenine monoxygenase diverts the kynurenine pathway toward the synthesis of Xanthurenic Acid, its inhibition may also contribute to glucose homeostasis.
