title: Characterization of the kynurenine pathway in human neurons.
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.
authors.affiliation: Department of Pharmacology, School of Medical Sciences, University of New South Wales, Sydney 2052, Australia. g.guillemin@cfi.unsw.edu.au
authors.forename: Gilles J
authors.initials: GJ
authors.lastname: Guillemin
authors.forename: Karen M
authors.initials: KM
authors.lastname: Cullen
authors.forename: Chai K
authors.initials: CK
authors.lastname: Lim
authors.forename: George A
authors.initials: GA
authors.lastname: Smythe
authors.forename: Brett
authors.initials: B
authors.lastname: Garner
authors.forename: Vimal
authors.initials: V
authors.lastname: Kapoor
authors.forename: Osamu
authors.initials: O
authors.lastname: Takikawa
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Brew
mesh_terms: D000328:Adult; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006801:Humans; D007737:Kynurenine / Q000235:genetics / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D007737:Kynurenine