β-Naphthoflavone and ethanol reverse mitochondrial dysfunction in a parkinsonian model of neurodegeneration
The 1-methyl-4-phenylpyridinium (MPP+) is a parkinsonian-inducing toxin that promotes neurodegeneration of dopaminergic cells by directly targeting complex I of mitochondria. Recently, it was reported that some Cytochrome P450 (CYP) isoforms, such as CYP 2D6 or 2E1, may be involved in the developmen...
| Autores: | , , , , |
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| Formato: | artículo |
| Fecha de publicación: | 2020 |
| País: | España |
| Recursos: | Universidad Pablo de Olavide (UPO) |
| Repositorio: | RIO. Repositorio Institucional Olavide |
| Idioma: | inglés |
| OAI Identifier: | oai:rio.upo.es:10433/22761 |
| Acesso em linha: | https://hdl.handle.net/10433/22761 |
| Access Level: | acceso abierto |
| Palavra-chave: | CYP 2D6 CYP 2E1 CYP induction Cytochrome P-450 system MPP+ toxicity Mitochondrial kinetics Neurodegeneration Neuroprotection |
| Resumo: | The 1-methyl-4-phenylpyridinium (MPP+) is a parkinsonian-inducing toxin that promotes neurodegeneration of dopaminergic cells by directly targeting complex I of mitochondria. Recently, it was reported that some Cytochrome P450 (CYP) isoforms, such as CYP 2D6 or 2E1, may be involved in the development of this neurodegenerative disease. In order to study a possible role for CYP induction in neurorepair, we designed an in vitro model where undifferentiated neuroblastoma SH-SY5Y cells were treated with the CYP inducers β-naphthoflavone (βNF) and ethanol (EtOH) before and during exposure to the parkinsonian neurotoxin, MPP+. The toxic effect of MPP+ in cell viability was rescued with both βNF and EtOH treatments. We also report that this was due to a decrease in reactive oxygen species (ROS) production, restoration of mitochondrial fusion kinetics, and mitochondrial membrane potential. These treatments also protected complex I activity against the inhibitory effects caused by MPP+, suggesting a possible neuroprotective role for CYP inducers. These results bring new insights into the possible role of CYP isoenzymes in xenobiotic clearance and central nervous system homeostasis. |
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