The neuroprotective role of ferrostatin-1 under rotenone-induced oxidative stress in dopaminergic neuroblastoma cells
| Autor: | Karine Fénelon, Michael S. Hwang, Carlos A. Valenzuela, Jose Eduardo Marin, David A. Ramirez, Mahesh Narayan, Parijat Kabiraj, Armando Varela-Ramirez, Lois Mendez, Rachid Skouta |
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| Rok vydání: | 2015 |
| Předmět: |
Dopamine
Bioengineering Apoptosis Phenylenediamines medicine.disease_cause Nitric Oxide Biochemistry Neuroprotection Analytical Chemistry chemistry.chemical_compound Neuroblastoma Cell Line Tumor Rotenone medicine Humans Protein disulfide-isomerase chemistry.chemical_classification Neurons Reactive oxygen species Cyclohexylamines Lipid peroxide Endoplasmic reticulum Organic Chemistry Endoplasmic Reticulum Stress Oxidative Stress Neuroprotective Agents chemistry Unfolded protein response Reactive Oxygen Species Oxidative stress |
| Zdroj: | The protein journal. 34(5) |
| ISSN: | 1875-8355 |
| Popis: | Endoplasmic reticulum (ER) proteins including protein disulfide isomerase (PDI) are playing crucial roles in maintaining appropriate protein folding. Under nitrosative stress, an excess of nitric oxide (NO) radical species induced the S-nitrosylation of PDI cysteines which eliminate its isomerase and oxidoreductase capabilities. In addition, the S-nitrosylation-PDI complex is the cause of aggregation especially of the α-synuclein (α-syn) protein (accumulation of Lewy-body aggregates). We recently identified a potent antioxidant small molecule, Ferrostatin-1 (Fer-1), that was able to inhibit a non-apoptotic cell death named ferroptosis. Ferroptosis cell death involved the generation of oxidative stress particularly lipid peroxide. In this work, we reported the neuroprotective role of ferrostatin-1 under rotenone-induced oxidative stress in dopaminergic neuroblastoma cells (SH-SY5Y). We first synthesized the Fer-1 and confirmed that it is not toxic toward the SH-SY5Y cells at concentrations up to 12.5 μM. Second, we showed that Fer-1 compound quenched the commercially available stable radical, the 2,2-diphenyl-1-picrylhydrazyl (DPPH), in non-cellular assay at 82 %. Third, Fer-1 inhibited the ROS/RNS generated under rotenone insult in SH-SY5Y cells. Fourth, we revealed the effective role of Fer-1 in ER stress mediated activation of apoptotic pathway. Finally, we reported that Fer-1 mitigated rotenone-induced α-syn aggregation. |
| Databáze: | OpenAIRE |
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