Characterization of the kynurenine pathway in human neurons

被引：242

作者：

Guillemin, Gilles J.

Cullen, Karen M.

Lim, Chai K.

Smythe, George A.

Garner, Brett

Kapoor, Vimal

Takikawa, Osamu

Brew, Bruce J.

机构：

[1] Univ New S Wales, Sch Med Sci, Dept Pharmacol, Sydney, NSW 2052, Australia

[2] Univ New S Wales, Biomed Mass Spectrometry Facil, Sydney, NSW 2052, Australia

[3] Univ Sydney, Sch Med Sci, Sydney, NSW 2006, Australia

[4] Univ Sydney, Bosch Inst, Sydney, NSW 2006, Australia

[5] St Vincents Hosp, Ctr Immunol, Sydney, NSW 2010, Australia

[6] St Vincents Hosp, Dept Neurol, Sydney, NSW 2010, Australia

[7] St Vincents Hosp, Dept HIV Med, Sydney, NSW 2010, Australia

[8] Prince Wales Med Res Inst, Randwick, NSW 2031, Australia

[9] Univ Western Australia, Dept Med & Pharmacol, Crawley, WA 6009, Australia

[10] Natl Inst Longev Sci, Natl Ctr Geriatr & Gerontol, Lab Radiat Safety, Morioka, Obu 4748511, Japan

来源：

JOURNAL OF NEUROSCIENCE | 2007年 / 27卷 / 47期

关键词：

human neurons; neuroblastoma; kynurenine pathway; indoleamine 2,3-dioxygenase; picolinic acid; quinolinic acid; neurotoxicity; tumor tolerance;

D O I：

10.1523/JNEUROSCI.4101-07.2007

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：12884 / 12892

页数：9

共 65 条

[21]

GUILLEMIN GJ, 2007, IN PRESS INT C, V1304

[22] Glial cell line-derived neurotrophic factor (GDNF) family ligands reduce the sensitivity of neuroblastoma cells to pharmacologically induced cell death, growth arrest and differentiation [J].