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
| Autor: | Peter R. Dunkley, Phillip W. Dickson, Fares Zeidán-Chuliá, José Cláudio Fonseca Moreira, Diana Carolina Rostirolla, Juciano Gasparotto, Rafael Calixto Bortolin, Alfeu Zanotto-Filho, Karina Klafke, Matheus Augusto de Bittencourt Pasquali, Lyvia Lintzmaier Petiz, Daniel Pens Gelain, Carolina Saibro Girardi, Alice Kunzler |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
SH-SY5Y Antioxidant Cell Survival medicine.medical_treatment Cell Neuroscience (miscellaneous) Retinoic acid Tretinoin Biology medicine.disease_cause Antioxidants 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound Cell Line Tumor medicine Humans Phosphorylation Extracellular Signal-Regulated MAP Kinases Cell Shape Protein kinase B Cell Proliferation Neurons Tyrosine hydroxylase Cell Cycle Cell Differentiation Molecular biology Mitochondria Up-Regulation Oxidative Stress Phenotype 030104 developmental biology medicine.anatomical_structure Neurology chemistry Reactive Oxygen Species Proto-Oncogene Proteins c-akt Biomarkers Oxidative stress Intracellular |
| Zdroj: | Molecular Neurobiology. 54:6903-6916 |
| ISSN: | 1559-1182 0893-7648 |
| Popis: | 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), β-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, β-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. |
| Databáze: | OpenAIRE |
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