The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Effects of all-trans-retinoic acid on human SH-SY5Y neuroblastoma as in vitro model in neurotoxicity research
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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“Nevertheless, the RA-induced activation of the two MAPK pathways is subsequent to the activation of upstream cascades involving Rho-GTPases ( 114, 115, 117 ), phosphoinositide 3-kinase (PI3K) and/or protein kinase B (PKB)/Akt ( 120, 121, 123 ), suggesting an atypical, nongenomic activation event similar to that described for steroid nuclear receptors ( 124, 125 ).”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [120]
In the citing paper
“However, in neuronal cells, Sertoli cells, and embryonic stem cells, RA instead activates the p42/p44 extracellular signal-regulated kinases (Erk) or classical MAPKs ( 116-122 ).”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [120]
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The SH-SY5Y cell line in Parkinson’s disease research: a systematic review
Xicoy, H., Wieringa, B., & Martens, G. J. M. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0149-0 · Cited by 1,036
Considerations for the use of SH-SY5Y neuroblastoma cells in neurobiology
Kovalevich, J., & Langford, D. (2013) · Methods in molecular biology · doi:10.1007/978-1-62703-640-5_2 · Cited by 1,005
Differentiation of the SH-SY5Y Human Neuroblastoma Cell Line
Shipley, M. M., Mangold, C. A., & SZPARA, M. L. (2016) · Journal of Visualized Experiments · doi:10.3791/53193 · Cited by 508
Retinoic acid receptors: From molecular mechanisms to cancer therapy
di Masi, A., Leboffe, L., De Marinis, E., Pagano, F., Cicconi, L., Rochette-Egly, C., Lo-Coco, F., Ascenzi, P., & Nervi, C. (2015) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2014.12.003 · Cited by 403
Vitamin A and retinoid signaling: genomic and nongenomic effects
Al Tanoury, Z., Piskunov, A., & Rochette-Egly, C. (2013) · Journal of Lipid Research · doi:10.1194/jlr.r030833 · Cited by 408
Metadata
- 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
- Venue
- NeuroToxicology
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 30
- Issue
- 1
- Pages
- 127-135
- ISSN
- 0161-813X (ISSN-L)
- 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
- 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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