Cited by 577Parkinson's Disease Mechanisms and TreatmentsNuclear Receptors and SignalingNeuroblastoma Research and Treatments

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

Cheung, Yuen-Ting, Lau, Way Kwok-Wai, Yu, Man-Shan, Lai, Cora Sau-Wan, Yeung, Sze-Chun, So, Kwok-Fai, Chang, Raymond Chuen-Chung·2009·NeuroToxicology

DOI 10.1016/j.neuro.2008.11.001

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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.

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Authors: Cheung, Y.-T., Lau, W. K.-W., Yu, M.-S., Lai, C. S.-W., Yeung, S.-C., So, K.-F., & Chang, R. C.-C.
Affiliations: University of Hong Kong (HK)
Corresponding author: Chang, Raymond Chuen-Chung
ORCID: Cheung, Yuen-Ting
Lau, Way Kwok-Wai
So, Kwok-Fai
Chang, Raymond Chuen-Chung
Venue: NeuroToxicology
Publisher: Elsevier BV
Published: 2009-01
Volume: 30
Issue: 1
Pages: 127-135
ISSN: 0161-813X (ISSN-L)
DOI: 10.1016/j.neuro.2008.11.001
OpenAlex: W2089425170
Cited by: 576
References: 61
Citations by year: 2026: 26 · 2025: 38 · 2024: 51 · 2023: 28 · 2022: 46 · 2021: 51 · 2020: 48 · 2019: 34 · 2018: 28 · 2017: 38 · 2016: 34 · 2015: 41 · 2014: 32 · 2013: 33 · 2012: 17
FWCI: 6.20
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: NeuroToxicology (publishedVersion)
PubMed (publishedVersion)
The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
Topics: Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Health Sciences › Medicine › Oncology › Neuroblastoma Research and Treatments
Keywords: all-trans retinoic acid, SH-SY5Y cells, neuroblastoma, neuronal differentiation, neurotoxicity, neuroprotection, Parkinson's disease, 6-hydroxydopamine, MPP+, Akt signaling, dopaminergic neurons, neuronal markers
MeSH terms: Cell Differentiation, Cells, Cultured, Humans, Models, Neurological, Neuroblastoma, Neurons, Tretinoin, Signal Transduction, Biomarkers, 1-Methyl-4-phenylpyridinium, Oxidopamine, Reactive Oxygen Species, Cell Line, Tumor

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

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