Biotin attenuation of oxidative stress, mitochondrial dysfunction, lipid metabolism alteration and 7ß-hydroxycholesterol-induced cell death in 158N murine oligodendrocytes.
Free Radic Res
; 53(5): 535-561, 2019 05.
Article
en En
| MEDLINE
| ID: mdl-31039616
Mitochondrial dysfunction and oxidative stress are involved in neurodegenerative diseases associated with an enhancement of lipid peroxidation products such as 7ß-hydroxycholesterol (7ß-OHC). It is, therefore, important to study the ability of 7ß-OHC to trigger mitochondrial defects, oxidative stress, metabolic dysfunctions and cell death, which are hallmarks of neurodegeneration, and to identify cytoprotective molecules. The effects of biotin were evaluated on 158N murine oligodendrocytes, which are myelin synthesizing cells, exposed to 7ß-OHC (50 µM) with or without biotin (10 and 100 nM) or α-tocopherol (positive control of cytoprotection). The effects of biotin on 7ß-OHC activities were determined using different criteria: cell adhesion; plasma membrane integrity; redox status. The impact on mitochondria was characterized by the measurement of transmembrane mitochondrial potential (ΔΨm), reactive oxygen species (ROS) overproduction, mitochondrial mass, quantification of cardiolipins and organic acids. Sterols and fatty acids were also quantified. Cell death (apoptosis, autophagy) was characterized by the enumeration of apoptotic cells, caspase-3 activation, identification of autophagic vesicles, and activation of LC3-I into LC3-II. Biotin attenuates 7ß-OHC-induced cytotoxicity: loss of cell adhesion was reduced; antioxidant activities were normalized. ROS overproduction, protein and lipid oxidation products were decreased. Biotin partially restores mitochondrial functions: attenuation of the loss of ΔΨm; reduced levels of mitochondrial O2â¢- overproduction; normalization of cardiolipins and organic acid levels. Biotin also normalizes cholesterol and fatty acid synthesis, and prevents apoptosis and autophagy (oxiapoptophagy). Our data support that biotin, which prevents oligodendrocytes damages, could be useful in the treatment of neurodegeneration and demyelination.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Biotina
/
Alfa-Tocoferol
/
Metabolismo de los Lípidos
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Hidroxicolesteroles
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Mitocondrias
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Antioxidantes
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Free Radic Res
Asunto de la revista:
BIOQUIMICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Reino Unido