Biotin attenuation of oxidative stress, mitochondrial dysfunction, lipid metabolism alteration and 7β-hydroxycholesterol-induced cell death in 158N murine oligodendrocytes

Abstract

Lizard (2019) Biotin attenuation of oxidative stress, mitochondrial dysfunction, lipid metabolism alteration and 7β-hydroxycholesterol-induced cell death in 158N murine oligodendrocytes, Free Radical Research, 53:5, 535-561, ABSTRACT Mitochondrial dysfunction and oxidative stress are involved in neurodegenerative diseases associated with an enhancement of lipid peroxidation products such as 7b-hydroxycholesterol (7b-OHC). It is, therefore, important to study the ability of 7b-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 7b-OHC (50 mM) with or without biotin (10 and 100 nM) or a-tocopherol (positive control of cytoprotection). The effects of biotin on 7b-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 (DWm), 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 7b-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 DWm; reduced levels of mitochondrial O 2 À 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. ARTICLE HISTORY

Gastric Electrical Pacing Reduces Apoptosis of Interstitial Cells of Cajal via Antioxidative Stress Effect Attributing to Phenotypic Polarization of M2 Macrophages in Diabetic Rats

“…In additional, we detected the ROS by flow cytometry and found that GEP could decrease the expression of ROS, suggesting that apoptosis of ICCs was reduced by GEP on the basis of lowering the ROS. This point coincides with the previous study [37].…”

7-Ketocholesterol and 7β-hydroxycholesterol: In vitro and animal models used to characterize their activities and to identify molecules preventing their toxicity

“…In 158N cells, anti-apoptotic and anti-oxidant capacities of natural or synthetic compounds and their ability to attenuate or to prevent toxicity of 7KC or 7β-OHC were often evaluated. In 158N cells incubated with 7KC or 7β-OHC, the cytoprotective effect of dimethylfumarate (DMF; Tecfidera) and biotin (vitamin B8), which are used for the treatment of MS, have been shown [120,121]. Natural products including argan oil, milk thistle seed oil, sea urchin egg oil, Carpobrotus edulis ethanol-water extract also strongly attenuate 7KC and/or 7β-OHC-induced cytotoxicity [121][122][123][124][125].…”

“…The schematic signaling pathways presented in Figure 3 summarize the data obtained with 7β-OHC on cells from different types and species: promonocytic / monocytic human U937 / THP1 cells [25,47]; vascular cells (endothelial and smooth muscle cells) [25,148]; wild type human mammary tumor MCF-7 cells (caspase-3 deficient), and genetically modified MCF-7 (MCF-7/c3: stably transfected with caspase-3) [138], human retinal pigment epithelial cells (ARPE-19) [100] / primary porcine retinal epithelial cells; rat C6 glioblastoma cells [171], murine oligodendrocytes 158N and murine microglial BV-2 cells [3,114,119,121,141,142]. The different cells used permitted determination of the signaling pathways involved in 7β-OHC-induced cytotoxicity and to define the relationships between ROS overproduction, apoptosis, autophagy and inflammation.…”

Effects of Biotin on survival, ensheathment, and ATP production by oligodendrocyte lineage cells in vitro

“…As shown in rat oligodendroglia, carboxylase activities are sensitive to levels of biotin availability [49]. Further, biotin can attenuate oxidative stress and mitochondrial dysfunction in murine oligodendrocytes [50].…”