Abstract
The involvement of astrocytes in Kynurenine pathway (KP) metabolism is still poorly understood. In the present study, we investigated the ability of human fetal astrocytes in vitro to produce quinolinic and picolinic acids using mass spectrometry. In parallel, we estimated the level of expression of five major KP enzymes using RT-PCR. The results demonstrated that astrocytes express most KP enzymes, except for kynurenine-hydroxylase. This in vitro study provides novel informations regarding the ability of human fetal astrocytes to degrade L-tryptophan along the KP.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bender D.A. and McCreanor, G.M., 1982, The preferred route of kynurenine metabolism in the rat, Biochem. Biophys. Acta 717:56–60.
Bignami A., Eng L.F., Dahl D., and Uyeda C.T., 1972, Localization of glial fibrillary acidic protein in astrocytes by immunofluorescence, Brain Res 43:429–435.
Brew B.J., Wesselingh S.L., Gonzales M., Heyes M.P., and Price R.W., 1996, How HIV leads to neurological disease, Med. J. Aust. 164:233–234.
Espey M.G., Chernyshev O.N., Reinhard J.J., Namboodiri M.A., and Colton C.A., 1997, Activated human microglia produce the excitotoxin quinolinic acid, Neuroreport 8:431–434.
Foster A.C., White R.J., and Schwarcz R., 1986, Synthesis of quinolinic acid by 3-hydroxyanthranilic acid oxygenase in rat brain tissue in vitro, J. Neurochem. 47:23–30.
Fukui S., Schwarcz R., Rapaort S.I., Takada Y., and Smith Q.R., 1991, Blood-Brain Barrier transport of Kynurenines: Implications for brain synthesis and metabolism., J. Neurochem. 56:2007–2017.
Guillemin G., Boussin F., Croitoru J., Le Grand R., and Dormont D., 1997, Obtention and characterization of astrocytes and microglia from adult monkey brains., J. Neurosc. Res. 49:576–591.
Heyes M.P., Saito K., and Crowley J.S., et al., 1992, Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease, Brain. 115:1249–1273.
Heyes M.P., Saito K., and Markey S.P., 1992, Human macrophages convert L-tryptophan into the neurotoxin quinolinic acid, Biochem. J. 283:633–635.
Heyes M.P., 1993, Metabolism and neuropathologic significance of quinolinic acid and kynurenic acid, Biochemical Soc. Trans. 21:83–89.
Heyes M.P., Achim C.L., Wiley C.A., Major E.O., Saito K., and Markey S.P., 1996, Human microglia convert L-tryptophan into the neurotoxin quinolinic acid, Biochem. J. 320:595–597.
Heyes M.P., Chen C.Y., Major E.O., and Saito K., 1997, Different kynurenine pathway enzymes limit quinolinic acid formation by various human cell types, Biochem. J. 326:351–356.
Heyes M.P., Saito K., and Chen C.Y., et al., 1997, Species heterogeneity between gerbils and rats: quinolinate production by microglia and astrocytes and accumulations in response to ischemic brain injury and systemic immune activation, J. Neurochem. 69:1519–1529.
Kohler C., Peterson A., Eriksson L.G., Okuno E., and Schwarcz R., 1988, Immunohistochemical identification of quinolinic acid phosphoribosyltransferase in glial cultures from rat brain, Neurosci Lett 84:115–9.
Koide Y. and Yoshida A., 1994, The signal transduction mechanism responsible for γ-IFN-induced indoleamine 2.3-dioxygenase gene expression, Infect. Immunity 62:948–955.
Pemberton A.L., Kerr S.J., Smythe G., and Brew B.J., 1997, Quinolinic acid production by macrophages stimulated with IFN-γ, TNF-α and IFN-α. J. Interferon & Cytokine Res. 17:589–595.
Roberts R.C., McCarthy K.E., Du F., Okuno E., and Schwarcz R, 1994, Immunocytochemical localization of the quinolinic acid synthesizing enzyme, 3-hydroxyanthranilic acid oxygenase, in the rat substantia nigra, Brain Res 650:229–238.
Saito K., Nowak T.S., and Suyama K., et al., 1993, Kynurenine pathway enzymes in brain: responses to ischaemic brain injury versus systemic immune activation, J. Neurochem. 61:2061–2070.
Saito K., Crowley J.S., Markey S.P., and Heyes M.P., 1993, A mechanism for increased quinolinic acid formation following acute systemic immune stimulation, J. Biol. Chem. 268:15496–15503.
Sanni L.A., Thomas S.R., and Tattam B.N., et al., 1998, Dramatic changes in oxidative tryptophan metabolism along the kynurenine pathway in experimental cerebral and non-cerebral malaria, Am. J. Pathol. 152:611–619.
Schwarcz R., Whetsell W.O.J., and Mangano R.M., 1983, Quinolinic acid: an endogenous metabolite that produces axon-sparing lesions in rat brain, Science 219:316–318.
Villinger F., Hunt D., Mayne A., Vuchetiv M., Findley H., and Ansari A.A., 1993, Qualitative and quantitative studies of cytokines synthetized and secreted by non-human primate peripheral blood mononuclear cells., Cytokine 5:169–179.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1999 Springer Science+Business Media New York
About this chapter
Cite this chapter
Guillemin, G.J., Kerr, S.J., Smythe, G.A., Armati, P.J., Brew, B.J. (1999). Kynurenine Pathway Metabolism in Human Astrocytes. In: Huether, G., Kochen, W., Simat, T.J., Steinhart, H. (eds) Tryptophan, Serotonin, and Melatonin. Advances in Experimental Medicine and Biology, vol 467. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4709-9_18
Download citation
DOI: https://doi.org/10.1007/978-1-4615-4709-9_18
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-7133-5
Online ISBN: 978-1-4615-4709-9
eBook Packages: Springer Book Archive