title: 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.
authors.affiliation: Laboratory of Neurodegenerative Diseases, Department of Anatomy, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Yuen-Ting
authors.initials: YT
authors.lastname: Cheung
authors.forename: Way Kwok-Wai
authors.initials: WK
authors.lastname: Lau
authors.forename: Man-Shan
authors.initials: MS
authors.lastname: Yu
authors.forename: Cora Sau-Wan
authors.initials: CS
authors.lastname: Lai
authors.forename: Sze-Chun
authors.initials: SC
authors.lastname: Yeung
authors.forename: Kwok-Fai
authors.initials: KF
authors.lastname: So
authors.forename: Raymond Chuen-Chung
authors.initials: RC
authors.lastname: Chang
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006801:Humans; D008959:Models, Neurological; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects; D016627:Oxidopamine / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D017382:Reactive Oxygen Species; D014212:Tretinoin; D016627:Oxidopamine; D015655:1-Methyl-4-phenylpyridinium