Characterization of the kynurenine pathway in human neurons

Gilles J. Guillemin*, Karen M. Cullen, Chai K. Lim, George A. Smythe, Brett Garner, Vimal Kapoor, Osamu Takikawa, Bruce J. Brew

*Corresponding author for this work

Research output: Contribution to journalArticle

197 Citations (Scopus)

Abstract

The kynurenine pathway is a major route of L-tryptophan catabolism producing neuroactive metabolites implicated in neurodegeneration and immune tolerance. We characterized the kynurenine pathway in human neurons and the human SK-N-SH neuroblastoma cell line and found that the kynurenine pathway enzymes were variably expressed. Picolinic carboxylase was expressed only in primary and some adult neurons but not in SK-N-SH cells. Because of this difference, SK-N-SH cells were able to produce the excitotoxin quinolinic acid, whereas human neurons produced the neuroprotectant picolinic acid. The net result of kynurenine pathway induction in human neurons is therefore predicted to result in neuroprotection, immune regulation, and tumor inhibition, whereas in SK-N-SH cells, it may result in neurotoxicity, immune tolerance, and tumor promotion. This study represents the first comprehensive characterization of the kynurenine pathway in neurons and the first description of the involvement of the kynurenine pathway as a mechanism for controlling both tumor cell neurotoxicity and persistence.

Original languageEnglish
Pages (from-to)12884-12892
Number of pages9
JournalJournal of Neuroscience
Volume27
Issue number47
DOIs
Publication statusPublished - 21 Nov 2007
Externally publishedYes

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    Guillemin, G. J., Cullen, K. M., Lim, C. K., Smythe, G. A., Garner, B., Kapoor, V., ... Brew, B. J. (2007). Characterization of the kynurenine pathway in human neurons. Journal of Neuroscience, 27(47), 12884-12892. https://doi.org/10.1523/JNEUROSCI.4101-07.2007