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Eur J Neurosci. 2017 Mar;45(5):700-711. doi: 10.1111/ejn.13499. Epub 2017 Jan 26.

Quinolinic acid induces neuritogenesis in SH-SY5Y neuroblastoma cells independently of NMDA receptor activation.

Author information

1
Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, West Medical Building, Glasgow, G12 8QQ, UK.
2
Internal Medicine, Ashtead Hospital, Ashtead, UK.

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 oxidizing conditions and affecting the availability of NAD+ , independently of NMDA receptors.

KEYWORDS:

NAD + ; differentiation; glutamate; kynurenines; nicotinamide

PMID:
27973747
DOI:
10.1111/ejn.13499
[Indexed for MEDLINE]

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