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Characterization of the kynurenine pathway in human neurons.

Journal Article


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.

UOW Authors


  •   Garner, Brett (external author)

Publication Date


  • 2007

Citation


  • 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.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 27(47), 12884-12892. doi:10.1523/jneurosci.4101-07.2007

Web Of Science Accession Number


Start Page


  • 12884

End Page


  • 12892

Volume


  • 27

Issue


  • 47

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.

UOW Authors


  •   Garner, Brett (external author)

Publication Date


  • 2007

Citation


  • 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.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 27(47), 12884-12892. doi:10.1523/jneurosci.4101-07.2007

Web Of Science Accession Number


Start Page


  • 12884

End Page


  • 12892

Volume


  • 27

Issue


  • 47