TY - JOUR
T1 - Characterization of the kynurenine pathway in human neurons
AU - Guillemin, Gilles J.
AU - Cullen, Karen M.
AU - Lim, Chai K.
AU - Smythe, George A.
AU - Garner, Brett
AU - Kapoor, Vimal
AU - Takikawa, Osamu
AU - Brew, Bruce J.
PY - 2007/11/21
Y1 - 2007/11/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=36448939072&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.4101-07.2007
DO - 10.1523/JNEUROSCI.4101-07.2007
M3 - Article
C2 - 18032661
AN - SCOPUS:36448939072
SN - 0270-6474
VL - 27
SP - 12884
EP - 12892
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 47
ER -