Activation of the kynurenine pathway and increased production of the excitotoxin quinolinic acid following traumatic brain injury in humans

Journal of Neuroinflammation

Maria Cristina Morganti-Kossmann³  Gilles J. Guillemin²  David W. Walker¹  Jeffrey V. Rosenfeld⁶  May Tan⁸  Gayathri Sundaram⁷  Benjamin Heng²  Chai K. Lim²  Tony Frugier⁵  Edwin B. Yan⁴ 

[1] The Ritchie Centre, Hudson Institute of Medical Research, Monash Medical Centre, Melbourne, Australia;Neuroinflammation group, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia;Australian New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia;Department of Physiology, Monash University, Clayton 3800, VIC, Australia;Department of Pharmacology and Therapeutics, The University of Melbourne, Melbourne, Australia;Department of Surgery, Central Clinical School and Monash Institute of Medical Engineering, Monash University, Melbourne, Australia;Applied Neurosciences Program, Peter Duncan Neurosciences Research Unit, St Vincent’s Centre for Applied Medical Research, Sydney, Australia;Hospital Queen Elizabeth, Karung Berkunci No. 2029, Kota Kinabalu, 88586, Sabah, Malaysia

关键词: Quinolinic acid;    Tryptophan metabolism;    Kynurenine pathway;    Traumatic brain injury;    Patients;   

Others  :  1221966
DOI  :  10.1186/s12974-015-0328-2

 received in 2014-11-18, accepted in 2015-05-20,  发布年份 2015

【 摘 要 】

During inflammation, the kynurenine pathway (KP) metabolises the essential amino acid tryptophan (TRP) potentially contributing to excitotoxicity via the release of quinolinic acid (QUIN) and 3-hydroxykynurenine (3HK). Despite the importance of excitotoxicity in the development of secondary brain damage, investigations on the KP in TBI are scarce. In this study, we comprehensively characterised changes in KP activation by measuring numerous metabolites in cerebrospinal fluid (CSF) from TBI patients and assessing the expression of key KP enzymes in brain tissue from TBI victims. Acute QUIN levels were further correlated with outcome scores to explore its prognostic value in TBI recovery.

【 授权许可】

   
2015 Yan et al.

【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

Fig. 5.

Fig. 6.

【 参考文献 】

• [1]Miller JD: Head injury. J Neurol Neurosurg Psychiatry 1993, 56:440-7.
• [2]Guillemin GJ: Quinolinic acid: neurotoxicity. FEBS J 2012, 279:1355.
• [3]McMenamy RH: Binding of indole analogues to human serum albumin. Effects of fatty acids. J Biol Chem 1965, 240:4235-43.
• [4]Christensen HN, Albritton LM, Kakuda DK, MacLeod CL: Gene-product designations for amino acid transporters. J Exp Biol 1994, 196:51-7.
• [5]Sarkhosh K, Tredget EE, Li Y, Kilani RT, Uludag H, Ghahary A: Proliferation of peripheral blood mononuclear cells is suppressed by the indoleamine 2,3-dioxygenase expression of interferon-gamma-treated skin cells in a co-culture system. Wound Repair Regen 2003, 11:337-45.
• [6]Sarkhosh K, Tredget EE, Karami A, Uludag H, Iwashina T, Kilani RT, et al.: Immune cell proliferation is suppressed by the interferon-gamma-induced indoleamine 2,3-dioxygenase expression of fibroblasts populated in collagen gel (FPCG). J Cell Biochem 2003, 90:206-17.
• [7]Meisel R, Zibert A, Laryea M, Gobel U, Daubener W, Dilloo D: Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood 2004, 103:4619-21.
• [8]Swanson KA, Zheng Y, Heidler KM, Mizobuchi T, Wilkes DS: CDllc + cells modulate pulmonary immune responses by production of indoleamine 2,3-dioxygenase. Am J Respir Cell Mol Biol 2004, 30:311-8.
• [9]Guillemin GJ, Brew BJ, Noonan CE, Takikawa O, Cullen KM: Indoleamine 2,3 dioxygenase and quinolinic acid immunoreactivity in Alzheimer’s disease hippocampus. Neuropathol Appl Neurobiol 2005, 31:395-404.
• [10]Schwarcz R, Bruno JP, Muchowski PJ, Wu HQ: Kynurenines in the mammalian brain: when physiology meets pathology. Nat Rev Neurosci 2012, 13:465-77.
• [11]Foster AC, Vezzani A, French ED, Schwarcz R: Kynurenic acid blocks neurotoxicity and seizures induced in rats by the related brain metabolite quinolinic acid. Neurosci Lett 1984, 48:273-8.
• [12]Heyes MP, Saito K, Crowley JS, Davis LE, Demitrack MA, Der M, et al.: Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease. Brain 1992, 115(Pt 5):1249-73.
• [13]Moroni F: Tryptophan metabolism and brain function: focus on kynurenine and other indole metabolites. Eur J Pharmacol 1999, 375:87-100.
• [14]Guillemin GJ, Brew BJ: Implications of the kynurenine pathway and quinolinic acid in Alzheimer’s disease. Redox Rep 2002, 7:199-206.
• [15]Ting KK, Brew B, Guillemin G: The involvement of astrocytes and kynurenine pathway in Alzheimer’s disease. Neurotox Res 2007, 12:247-62.
• [16]Guillemin GJ, Williams KR, Smith DG, Smythe GA, Croitoru-Lamoury J, Brew BJ: Quinolinic acid in the pathogenesis of Alzheimer’s disease. Adv Exp Med Biol 2003, 527:167-76.
• [17]Guillemin GJ: Quinolinic acid, the inescapable neurotoxin. FEBS J 2012, 279:1356-65.
• [18]Heyes MP, Brew BJ, Martin A, Price RW, Salazar AM, Sidtis JJ, et al.: Quinolinic acid in cerebrospinal fluid and serum in HIV-1 infection: relationship to clinical and neurological status. Ann Neurol 1991, 29:202-9.
• [19]Baratte S, Molinari A, Veneroni O, Speciale C, Benatti L, Salvati P: Temporal and spatial changes of quinolinic acid immunoreactivity in the gerbil hippocampus following transient cerebral ischemia. Brain Res Mol Brain Res 1998, 59:50-7.
• [20]Haberny KA, Pou S, Eccles CU: Potentiation of quinolinate-induced hippocampal lesions by inhibition of NO synthesis. Neurosci Lett 1992, 146:187-90.
• [21]Kheramin S, Body S, Mobini S, Ho MY, Velazquez-Martinez DN, Bradshaw CM, et al.: Effects of quinolinic acid-induced lesions of the orbital prefrontal cortex on inter-temporal choice: a quantitative analysis. Psychopharmacology (Berl) 2002, 165:9-17.
• [22]Yan E, Castillo-Melendez M, Smythe G, Walker D: Quinolinic acid promotes albumin deposition in Purkinje cell, astrocytic activation and lipid peroxidation in fetal brain. Neuroscience 2005, 134:867-75.
• [23]Stone TW: Kynurenines in the CNS: from endogenous obscurity to therapeutic importance. Prog Neurobiol 2001, 64:185-218.
• [24]Stone TW, Perkins MN: Quinolinic acid: a potent endogenous excitant at amino acid receptors in CNS. Eur J Pharmacol 1981, 72:411-2.
• [25]Kalonia H, Kumar P, Kumar A, Nehru B: Effect of caffeic acid and rofecoxib and their combination against intrastriatal quinolinic acid induced oxidative damage, mitochondrial and histological alterations in rats. Inflammopharmacology 2009, 17:211-9.
• [26]Braidy N, Grant R, Adams S, Brew BJ, Guillemin GJ: Mechanism for quinolinic acid cytotoxicity in human astrocytes and neurons. Neurotox Res 2009, 16:77-86.
• [27]Kerr SJ, Armati PJ, Guillemin GJ, Brew BJ: Chronic exposure of human neurons to quinolinic acid results in neuronal changes consistent with AIDS dementia complex. AIDS 1998, 12:355-63.
• [28]Bell MJ, Kochanek PM, Heyes MP, Wisniewski SR, Sinz EH, Clark RS, et al.: Quinolinic acid in the cerebrospinal fluid of children after traumatic brain injury. Crit Care Med 1999, 27:493-7.
• [29]Sinz EH, Kochanek PM, Heyes MP, Wisniewski SR, Bell MJ, Clark RS, et al.: Quinolinic acid is increased in CSF and associated with mortality after traumatic brain injury in humans. J Cereb Blood Flow Metab 1998, 18:610-5.
• [30]Costantino G: Inhibitors of quinolinic acid synthesis: new weapons in the study of neuroinflammatory diseases. Future Med Chem 2014, 6:841-3.
• [31]Wilson JT, Pettigrew LE, Teasdale GM: Structured interviews for the Glasgow Outcome Scale and the extended Glasgow Outcome Scale: guidelines for their use. J Neurotrauma 1998, 15:573-85.
• [32]Darlington LG, Mackay GM, Forrest CM, Stoy N, George C, Stone TW: Altered kynurenine metabolism correlates with infarct volume in stroke. Eur J Neurosci 2007, 26:2211-21.
• [33]Smythe GA, Braga O, Brew BJ, Grant RS, Guillemin GJ, Kerr SJ, et al.: Concurrent quantification of quinolinic, picolinic, and nicotinic acids using electron-capture negative-ion gas chromatography–mass spectrometry. Anal Biochem 2002, 301:21-6.
• [34]Frugier T, Conquest A, McLean C, Currie P, Moses D, Goldshmit Y: Expression and activation of EphA4 in the human brain after traumatic injury. J Neuropathol Exp Neurol 2012, 71:242-50.
• [35]Frugier T, Crombie D, Conquest A, Tjhong F, Taylor C, Kulkarni T, et al.: Modulation of LPA receptor expression in the human brain following neurotrauma. Cell Mol Neurobiol 2011, 31:569-77.
• [36]Frugier T, Morganti-Kossmann C, O’Reilly D, McLean C: In situ detection of inflammatory mediators in post-mortem human brain tissue following traumatic injury. J Neurotrauma 2010, 27:497-507.
• [37]Nemeth H, Toldi J, Vecsei L: Role of kynurenines in the central and peripheral nervous systems. Curr Neurovasc Res 2005, 2:249-60.
• [38]Werner C, Engelhard K: Pathophysiology of traumatic brain injury. Br J Anaesth 2007, 99:4-9.
• [39]Fallarino F, Grohmann U, Puccetti P: Indoleamine 2,3-dioxygenase: from catalyst to signaling function. Eur J Immunol 2012, 42:1932-7.
• [40]Salazar C, Hofer T: Multisite protein phosphorylation–from molecular mechanisms to kinetic models. FEBS J 2009, 276:3177-98.
• [41]Ziebell JM, Morganti-Kossmann MC: Involvement of pro- and anti-inflammatory cytokines and chemokines in the pathophysiology of traumatic brain injury. Neurotherapeutics 2010, 7:22-30.
• [42]Woodcock T, Morganti-Kossmann MC: The role of markers of inflammation in traumatic brain injury. Front Neurol 2013, 4:18.
• [43]Yamada A, Akimoto H, Kagawa S, Guillemin GJ, Takikawa O: Proinflammatory cytokine interferon-gamma increases induction of indoleamine 2,3-dioxygenase in monocytic cells primed with amyloid beta peptide 1–42: implications for the pathogenesis of Alzheimer’s disease. J Neurochem 2009, 110:791-800.
• [44]Yan EB, Satgunaseelan L, Paul E, Bye N, Nguyen P, Agyapomaa D, et al.: Post-traumatic hypoxia is associated with prolonged cerebral cytokine production, higher serum biomarker levels, and poor outcome in patients with severe traumatic brain injury. J Neurotrauma 2014, 31:618-29.
• [45]Wang Y, Lawson MA, Dantzer R, Kelley KW: LPS-induced indoleamine 2,3-dioxygenase is regulated in an interferon-gamma-independent manner by a JNK signaling pathway in primary murine microglia. Brain Behav Immun 2010, 24:201-9.
• [46]Ploder M, Spittler A, Schroecksnadel K, Neurauter G, Pelinka LE, Roth E, et al.: Tryptophan degradation in multiple trauma patients: survivors compared with non-survivors. Clin Sci (Lond) 2009, 116:593-8.
• [47]Pellegrin K, Neurauter G, Wirleitner B, Fleming AW, Peterson VM, Fuchs D: Enhanced enzymatic degradation of tryptophan by indoleamine 2,3-dioxygenase contributes to the tryptophan-deficient state seen after major trauma. Shock 2005, 23:209-15.
• [48]Pfefferkorn ER: Interferon gamma blocks the growth of Toxoplasma gondii in human fibroblasts by inducing the host cells to degrade tryptophan. Proc Natl Acad Sci U S A 1984, 81:908-12.
• [49]Han Q, Cai T, Tagle DA, Li J: Structure, expression, and function of kynurenine aminotransferases in human and rodent brains. Cell Mol Life Sci 2010, 67:353-68.
• [50]Han Q, Cai T, Tagle DA, Robinson H, Li J: Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II. Biosci Rep 2008, 28:205-15.
• [51]Zwilling D, Huang SY, Sathyasaikumar KV, Notarangelo FM, Guidetti P, Wu HQ, et al.: Kynurenine 3-monooxygenase inhibition in blood ameliorates neurodegeneration. Cell 2011, 145:863-74.
• [52]Darlington LG, Forrest CM, Mackay GM, Smith RA, Smith AJ, Stoy N, et al.: On the Biological Importance of the 3-hydroxyanthranilic Acid: anthranilic acid ratio. Int J Tryptophan Res 2010, 3:51-9.
• [53]Forrest CM, Mackay GM, Oxford L, Stoy N, Stone TW, Darlington LG: Kynurenine pathway metabolism in patients with osteoporosis after 2 years of drug treatment. Clin Exp Pharmacol Physiol 2006, 33:1078-87.
• [54]Stoy N, Mackay GM, Forrest CM, Christofides J, Egerton M, Stone TW, et al.: Tryptophan metabolism and oxidative stress in patients with Huntington’s disease. J Neurochem 2005, 93:611-23.
• [55]Forrest CM, Mackay GM, Stoy N, Spiden SL, Taylor R, Stone TW, et al.: Blood levels of kynurenines, interleukin-23 and soluble human leucocyte antigen-G at different stages of Huntington’s disease. J Neurochem 2010, 112:112-22.
• [56]Mackay GM, Forrest CM, Christofides J, Bridel MA, Mitchell S, Cowlard R, et al.: Kynurenine metabolites and inflammation markers in depressed patients treated with fluoxetine or counselling. Clin Exp Pharmacol Physiol 2009, 36:425-35.
• [57]Guillemin GJ, Cullen KM, Lim CK, Smythe GA, Garner B, Kapoor V, et al.: Characterization of the kynurenine pathway in human neurons. J Neurosci 2007, 27:12884-92.
• [58]Schwarcz R, Whetsell WO Jr, Mangano RM: Quinolinic acid: an endogenous metabolite that produces axon-sparing lesions in rat brain. Science 1983, 219:316-8.
• [59]Whetsell WO Jr, Schwarcz R: Prolonged exposure to submicromolar concentrations of quinolinic acid causes excitotoxic damage in organotypic cultures of rat corticostriatal system. Neurosci Lett 1989, 97:271-5.
• [60]Beal MF, Kowall NW, Ellison DW, Mazurek MF, Swartz KJ, Martin JB: Replication of the neurochemical characteristics of Huntington’s disease by quinolinic acid. Nature 1986, 321:168-71.
• [61]Vandresen-Filho S, Martins WC, Bertoldo DB, Mancini G, De Bem AF, Tasca CI. Cerebral cortex, hippocampus, striatum and cerebellum show differential susceptibility to quinolinic acid-induced oxidative stress. Neurol Sci 2015.
• [62]Chen Y, Brew BJ, Guillemin GJ: Characterization of the kynurenine pathway in NSC-34 cell line: implications for amyotrophic lateral sclerosis. J Neurochem 2011, 118:816-25.
• [63]Iwahashi H, Kawamori H, Fukushima K: Quinolinic acid, alpha-picolinic acid, fusaric acid, and 2,6-pyridinedicarboxylic acid enhance the Fenton reaction in phosphate buffer. Chem Biol Interact 1999, 118:201-15.
• [64]Santamaria A, Galvan-Arzate S, Lisy V, Ali SF, Duhart HM, Osorio-Rico L, et al.: Quinolinic acid induces oxidative stress in rat brain synaptosomes. Neuroreport 2001, 12:871-4.
• [65]Santamaria A, Jimenez-Capdeville ME, Camacho A, Rodriguez-Martinez E, Flores A, Galvan-Arzate S: In vivo hydroxyl radical formation after quinolinic acid infusion into rat corpus striatum. Neuroreport 2001, 12:2693-6.
• [66]von Ruecker AA, Han-Jeon BG, Wild M, Bidlingmaier F: Protein kinase C involvement in lipid peroxidation and cell membrane damage induced by oxygen-based radicals in hepatocytes. Biochem Biophys Res Commun 1989, 163:836-42.
• [67]Goda K, Kishimoto R, Shimizu S, Hamane Y, Ueda M: Quinolinic acid and active oxygens. Possible contribution of active oxygens during cell death in the brain. Adv Exp Med Biol 1996, 398:247-54.
• [68]Chen Y, Stankovic R, Cullen KM, Meininger V, Garner B, Coggan S, et al.: The kynurenine pathway and inflammation in amyotrophic lateral sclerosis. Neurotox Res 2010, 18:132-42.
• [69]Martin A, Heyes MP, Salazar AM, Kampen DL, Williams J, Law WA, et al.: Progressive slowing of reaction time and increasing cerebrospinal fluid concentrations of quinolinic acid in HIV-infected individuals. J Neuropsychiatry Clin Neurosci 1992, 4:270-9.