Hernandez-Martinez, J.-M., Forrest, C. M., Darlington, L. G., Smith, R. A. and Stone, T. W. (2017) Quinolinic acid induces neuritogenesis in SH-SY5Y neuroblastoma cells independently of NMDA receptor activation. European Journal of Neuroscience, 45(5), pp. 700-711. (doi: 10.1111/ejn.13499) (PMID:27973747)
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Abstract
Glutamate and nicotinamide adenine dinucleotide (NAD+) have been implicated in neuronal development and several types of cancer. The kynurenine pathway of tryptophan metabolism includes quinolinic acid (QA) which is both a selective agonist at N-methyl-D-aspartate (NMDA) receptors and also a precursor for the formation of NAD+. The effect of QA on cell survival and differentiation has therefore been examined on SH-SY5Y human neuroblastoma cells. Retinoic acid (RA, 10 μM) induced differentiation of SH-SY5Y cells into a neuronal phenotype showing neurite growth. QA (50-150 nM) also caused a concentration-dependent increase in the neurite/soma ratio, indicating differentiation. Both RA and QA increased expression of the neuronal marker β3-tubulin in whole-cell homogenates and in the neuritic fraction assessed using a neurite outgrowth assay. Expression of the neuronal proliferation marker doublecortin revealed that, unlike RA, QA did not decrease the number of mitotic cells. QA-induced neuritogenesis coincided with an increase in the generation of reactive oxygen species. Neuritogenesis was prevented by diphenylene-iodonium (an inhibitor of NADPH oxidase) and superoxide dismutase, supporting the involvement of reactive oxygen species. NMDA itself did not promote neuritogenesis and the NMDA antagonist dizocilpine (MK-801) did not prevent quinolinate-induced neuritogenesis, indicating that the effects of QA were independent of NMDA receptors. Nicotinamide caused a significant increase in the neurite/soma ratio and the expression of β3-tubulin in the neuritic fraction. Taken together, these results suggest that QA induces neuritogenesis by promoting oxidising conditions and affecting the availability of NAD+, independently of NMDA receptors.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Forrest, Dr Caroline and Stone, Professor Trevor and Smith, Professor Robert and Darlington, Dr Lynda |
| Authors: | Hernandez-Martinez, J.-M., Forrest, C. M., Darlington, L. G., Smith, R. A., and Stone, T. W. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience |
| Journal Name: | European Journal of Neuroscience |
| Publisher: | Wiley |
| ISSN: | 0953-816X |
| ISSN (Online): | 1460-9568 |
| Published Online: | 14 December 2016 |
| Copyright Holders: | Copyright © 2016 Wiley |
| First Published: | First published in European Journal of Neuroscience 45(5):700-711 |
| Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
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