Induction of peroxisomal changes in oligodendrocytes treated with 7-ketocholesterol: Attenuation by α-tocopherol

Nury

et al. 2019

Free Radical Research

Self Cite

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

Section: Discussionmentioning

confidence: 81%

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

Sghaier

Nury

et al. 2019

Free Radical Research

Self Cite

“…Since Olea europaea leaf infusions had a high amount of polyphenols, they could be used as an alternative for Vit E, known as the most potent antioxidant molecule. Indeed, Vit E was able to counteract 7‐ketocholesterol‐induced cell death as well as the associated mitochondrial dysfunctions in the same cell line used in this study (Nury et al., 2018). On the basis of this experiment, which has been frequently used to assess the cytoprotective effects of different compounds, the Olea europaea leaf infusions were used in this study.…”

Section: Resultsmentioning

confidence: 61%

Phytochemical profile, cytotoxic, antioxidant, and allelopathic potentials of aqueous leaf extracts of Olea europaea

Zaïri

Nouir

Food Science & Nutrition

et al. 2020

Self Cite

Although bioactivities of Olea europaea (OE) have been widely described, most of them were related to its methanolic extracts or its essential oils, While data related to aqueous extracts still very scarce. Thus, in this study, the phytochemical composition, the antioxidant activity, the cytotoxic potential, and the allelopathic potential of aqueous leaf extracts from two varieties of Olea europaea were investigated and compared. High‐performance liquid chromatography (HPLC) was used to identify and quantify the constituents of the tested plants, and spectrophotometric methods to evaluate antioxidant activities. The cytotoxic potential was investigated using murine oligodendrocytes (158N) while germination seeds’ test was used for allelopathic activity. HPLC analysis showed the presence of 10 phenolic compounds in both extracts. Chemlali variety showed the highest antioxidant and allelopathic activities. Regarding the cytotoxicity effect, a significant increase in cell viability was observed with both of our extracts compared to untreated cells. These results confirm that aqueous extracts from OE produce a range of substances with potential antioxidant, antifungal, and allelopathic effects without toxic effects. Thus, they could be used as an alternative of chemical compounds.

“…Indirect immunofluorescence with an antibody raised against the ATP binding cassette subfamily D member (ABCD)3 peroxisomal transporter was used to detect the peroxisomes [ 76 , 77 ]. Adherent and non-adherent cells were collected and fixed with freshly prepared 2% ( w/v ) paraformaldehyde (Sigma-Aldrich) diluted in PBS for 15 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Prevention by Dietary Polyphenols (Resveratrol, Quercetin, Apigenin) Against 7-Ketocholesterol-Induced Oxiapoptophagy in Neuronal N2a Cells: Potential Interest for the Treatment of Neurodegenerative and Age-Related Diseases

Yammine

Nury

et al. 2020

Cells

Self Cite

The Mediterranean diet is associated with health benefits due to bioactive compounds such as polyphenols. The biological activities of three polyphenols (quercetin (QCT), resveratrol (RSV), apigenin (API)) were evaluated in mouse neuronal N2a cells in the presence of 7-ketocholesterol (7KC), a major cholesterol oxidation product increased in patients with age-related diseases, including neurodegenerative disorders. In N2a cells, 7KC (50 µM; 48 h) induces cytotoxic effects characterized by an induction of cell death. When associated with RSV, QCT and API (3.125; 6.25 µM), 7KC-induced toxicity was reduced. The ability of QCT, RSV and API to prevent 7KC-induced oxidative stress was characterized by a decrease in reactive oxygen species (ROS) production in whole cells and at the mitochondrial level; by an attenuation of the increase in the level and activity of catalase; by attenuating the decrease in the expression, level and activity of glutathione peroxidase 1 (GPx1); by normalizing the expression, level and activity of superoxide dismutases 1 and 2 (SOD1, SOD2); and by reducing the decrease in the expression of nuclear erythroid 2-like factor 2 (Nrf2) which regulates antioxidant genes. QCT, RSV and API also prevented mitochondrial dysfunction in 7KC-treated cells by counteracting the loss of mitochondrial membrane potential (ΨΔm) and attenuating the decreased gene expression and/or protein level of AMP-activated protein kinase α (AMPKα), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) implicated in mitochondrial biogenesis. At the peroxisomal level, QCT, RSV and API prevented the impact of 7KC by counteracting the decrease in ATP binding cassette subfamily D member (ABCD)3 (a peroxisomal mass marker) at the protein and mRNA levels, as well as the decreased expresssion of genes associated with peroxisomal biogenesis (Pex13, Pex14) and peroxisomal β-oxidation (Abcd1, Acox1, Mfp2, Thiolase A). The 7KC-induced decrease in ABCD1 and multifunctional enzyme type 2 (MFP2), two proteins involved in peroxisomal β-oxidation, was also attenuated by RSV, QCT and API. 7KC-induced cell death, which has characteristics of apoptosis (cells with fragmented and/or condensed nuclei; cleaved caspase-3; Poly(ADP-ribose) polymerase (PARP) fragmentation) and autophagy (cells with monodansyl cadaverine positive vacuoles; activation of microtubule associated protein 1 light chain 3–I (LC3-I) to LC3-II, was also strongly attenuated by RSV, QCT and API. Thus, in N2a cells, 7KC induces a mode of cell death by oxiapoptophagy, including criteria of OXIdative stress, APOPTOsis and autoPHAGY, associated with mitochondrial and peroxisomal dysfunction, which is counteracted by RSV, QCT, and API reinforcing the interest for these polyphenols in prevention of diseases associated with increased 7KC levels.