- Title
- Changes in cell cycle and up-regulation of neuronal markers during SH-SY5Y neurodifferentiation by retinoic acid are mediated by reactive species production and oxidative stress
- Creator
- Kunzler, Alice; Zeidán-Chuliá, Fares; Dickson, Phillip; Dunkley, Peter; Moreira, José Cláudio Fonesca; Gelain, Daniel Pens; Gasparotto, Juciano; Girardi, Carolina Saibro; Klafke, Karina; Petiz, Lyvia Lintzmaier; Bortolin, Rafael Calixto; Rostirolla, Diana Carolina; Zanotto-Filho, Alfeu; de Bittencourt Pasquali, Matheus Augusto
- Relation
- Molecular Neurobiology Vol. 54, Issue 9, p. 6903-6916
- Publisher Link
- http://dx.doi.org/10.1007/s12035-016-0189-4
- Publisher
- Springer
- Resource Type
- journal article
- Date
- 2017
- Description
- Human neuroblastoma SH-SY5Y cells have been used as an in vitro model for neurodegenerative disorders such as Parkinson's disease and can be induced to a mature neuronal phenotype through retinoic acid (RA) differentiation. However, mechanisms of RA-induced differentiation remain unclear. Here, we investigate the role of reactive species (RS) on SH-SY5Y neuroblastoma cells under RA differentiation, using the antioxidant Trolox® as co-treatment. We found that RA treatment for 7 days reduced the cell number and proliferative capacity and induced the expression of adult catecholaminergic/neuronal markers such as tyrosine hydroxylase (TH), ß-III tubulin, and enolase-2. Evaluation of intracellular RS production by DCFH oxidation assay and quantification of cell non-enzymatic antioxidant activity by TRAP demonstrated that RA increases RS production. Furthermore, mitochondrial NADH oxidation showed to be inhibited under differentiation with RA. Cells subjected to co-treatment with antioxidant Trolox® demonstrated a remaining proliferative capacity and a decrease in the pro-oxidant state and RS production. Besides, antioxidant treatment restores the mitochondrial NADH oxidation. Importantly, Trolox® co-treatment inhibited the appearance of morphological characteristics such as neurite extension and branching, and decreased the expression of TH, ß-III tubulin, and enolase-2 after a seven-day differentiation with RA, indicating that RS production is a necessary step in this process. Trolox® also inhibited the phosphorylation of Akt and ERK1/2, which are involved in differentiation and survival, respectively, of these cells. Altogether, these data indicate the presence of a redox-dependent mechanism in SH-SY5Y RA-differentiation process and can be a useful insight to improve understanding of neuronal differentiation signaling.
- Subject
- retinoic acid; neuronal differentiation; SH-SY5Y; oxidative stress; tyrosine hydroxylase
- Identifier
- http://hdl.handle.net/1959.13/1392096
- Identifier
- uon:33343
- Identifier
- ISSN:0893-7648
- Language
- eng
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