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]
Citations
Cites
NeuN, a neuronal specific nuclear protein in vertebratesxs
Mullen, R. J., Buck, C. R., & Smith, A. M. (1992) · Development · doi:10.1242/dev.116.1.201 · Cited by 2,351
Encinas, M., Iglesias, M., Liu, Y., Wang, H., Muhaisen, A., Ceña, V., Gallego, C., & Comella, J. X. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0750991.x · Cited by 822
Påhlman, S., Ruusala, A.-I., Abrahamsson, L., Mattsson, M. E. K., & Esscher, T. (1984) · Cell Differentiation · doi:10.1016/0045-6039(84)90038-1 · Cited by 571
Levites, Y., Amit, T., Youdim, M. B. H., & Mandel, S. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202832200 · Cited by 417
Levites, Y., Amit, T., Mandel, S. A., & Youdim, M. B. H. (2003) · The FASEB Journal · doi:10.1096/fj.02-0881fje · Cited by 372
López‐Carballo, G., Moreno, L., Masiá, S., Pérez, P., & Barettino, D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201869200 · Cited by 301
Rehm, H., Wiedenmann, B., & Betz, H. (1986) · The EMBO Journal · doi:10.1002/j.1460-2075.1986.tb04243.x · Cited by 297
Levites, Y., Youdim, M. B. H., Maor, G., & Mandel, S. (2002) · Biochemical Pharmacology · doi:10.1016/s0006-2952(01)00813-9 · Cited by 291
Developmental and cell type‐specific expression of the neuronal marker NeuN in the murine cerebellum
Weyer, A., & Schilling, K. (2003) · Journal of Neuroscience Research · doi:10.1002/jnr.10655 · Cited by 266
Yu, M.-S., Leung, S. K., Lai, S.-W., Che, C., Zee, S., So, K., Yuen, W.-H., & Chang, R. C. (2005) · Experimental Gerontology · doi:10.1016/j.exger.2005.06.010 · Cited by 203
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Nicaise, A. M. (2013) · Trinity College Digital Repository (Trinity College, Hartford CT)
Sisnaiske, J., Frimat, J., Hengstler, J. G., West, J. J., & van Thriel, C. (2010) · Nachrichten aus der Chemie · doi:10.1002/nadc.201075611
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Dwane, S. (2013) · University of Limerick Institutional Repository (University of Limerick) · doi:10.34961/6252
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[Bacteremia associated with implantable device for central venous access caused by Bacillus cereus].
Ramos, J. M., Bernacer, M., Fernández-Roblas, R., & Soriano, F. (1996) · PubMed
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Looyenga, B. D., Resau, J. H., & MacKeigan, J. P. (2014) · PLoS ONE · doi:10.1371/annotation/7a99f22f-8273-43c0-b78f-8675ee409bf6
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Ritter, M., Stojanović, N., Zschieschang, S., Grader, J., Assasa, M. N., Buhl, E. M., Coschiera, A., Schillberg, S., Schuphan, J., & Fischer, H. (2025) · Small · doi:10.1002/smll.202509395
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Nagamani, T. S., Guruprasad, N. M., & R, M. K. (2026) · Research Journal of Pharmacy and Technology · doi:10.52711/0974-360x.2026.00222
Dong, R., Zhou, L., Wang, H., Ruan, S., Meng, X., Feng, J., & 杨玉社 (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c00264
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Ciccone, L., Petrarolo, G., D’Agostino, I., Scianò, F., Bernardoni, B. L., Leri, M., Ann, J., Nencetti, S., Lee, J., Bucciantini, M., et al. (2026) · Antioxidants · doi:10.3390/antiox15070857
Manna, S., Kirtana, R., Baral, T., Mishra, J., Nandi, P., Chakraborty, S., Mahto, N., Roy, A., Mishra, P., Pradhan, B., et al. (2026) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2026.120192
Wu, Y., Lin, C., Huang, P.-S., Chao, C., Lin, T., Chen, W.-L., Chen, C., Chang, K., Lee, M.-C., Chen, I., et al. (2026) · Aging · doi:10.18632/aging.206409
Çağlar, Ö., & Türkez, H. (2026) · Applied Biochemistry and Biotechnology · doi:10.1007/s12010-026-05878-5
Singh, S., Bir, A., Thakur, R., Chauhan, A., Ghosh, A., Mittal, A., Nayak, A. K., Chakrabarti, S. S., & Chakrabarti, S. (2026) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2026.102783
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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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