Effects of all-trans-retinoic acid on human SH-SY5Y neuroblastoma as in vitro model in neurotoxicity research

Yuen-Ting CHEUNG, Kwok Wai LAU, Man-Shan YU, Cora Sau-Wan LAI, Sze-Chun YEUNG, Kwok-Fai SO, Raymond Chuen-Chung CHANG

Research output: Contribution to journalArticles

293 Citations (Scopus)

Abstract

Human neuroblastoma SH-SY5Y is a dopaminergic neuronal cell line which has been used as an in vitro model for neurotoxicity experiments. Although the neuroblastoma is usually differentiated by all-trans-retinoic acid (RA), both RA-differentiated and undifferentiated SH-SY5Y cells have been used in neuroscience research. However, the changes in neuronal properties triggered by RA as well as the subsequent responsiveness to neurotoxins have not been comprehensively studied. Therefore, we aim to re-evaluate the differentiation property of RA on this cell line. We hypothesize that modulation of signaling pathways and neuronal properties during RA-mediated differentiation in SH-SY5Y cells can affect their susceptibility to neurotoxins. The differentiation property of RA was confirmed by showing an extensive outgrowth of neurites, increased expressions of neuronal nuclei, neuron specific enolase, synaptophysin and synaptic associated protein-97, and decreased expression of inhibitor of differentiation-1. While undifferentiated SH-SY5Y cells were susceptible to 6-OHDA and MPP⁺, RA-differentiation conferred SH-SY5Y cells higher tolerance, potentially by up-regulating survival signaling, including Akt pathway as inhibition of Akt removed RA-induced neuroprotection against 6-OHDA. As a result, the real toxicity cannot be revealed in RA-differentiated cells. Therefore, undifferentiated SH-SY5Y is more appropriate for studying neurotoxicity or neuroprotection in experimental Parkinson's disease research. Copyright © 2008 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)127-135
JournalNeuroToxicology
Volume30
Issue number1
DOIs
Publication statusPublished - Jan 2009

Citation

Cheung, Y.-T., Lau, W. K.-W., Yu, M.-S., Lai, C. S.-W., Yeung, S.-C., So, K.-F., & Chang, R. C.-C. (2009). Effects of all-trans-retinoic acid on human SH-SY5Y neuroblastoma as in vitro model in neurotoxicity research. NeuroToxicology, 30(1), 127-135. doi: 10.1016/j.neuro.2008.11.001

Keywords

  • Differentiation
  • Neuroblastoma
  • Neurotoxicity
  • Retinoic acid
  • 6-Hydroxydopamine
  • MPP+

Fingerprint Dive into the research topics of 'Effects of all-trans-retinoic acid on human SH-SY5Y neuroblastoma as in vitro model in neurotoxicity research'. Together they form a unique fingerprint.