Protective Effects of α-Tocopherol, γ-Tocopherol and Oleic Acid, Three Compounds of Olive Oils, and No Effect of Trolox, on 7-Ketocholesterol-Induced Mitochondrial and Peroxisomal Dysfunction in Microglial BV-2 Cells.

Meryam Debbabi (1, 2) , Thomas Nury (1) , Amira Zarrouk (3, 1, 2) , Nadia Mekahli (1) , Maryem Bezine (1, 4, 5) , Randa Sghaier (1, 3) , Stéphane Grégoire (6) , Lucy Martine (6) , Philippe Durand (7) , Emmanuelle Camus (7) , Anne Vejux (1) , Aymen Jabrane , Lionel Brétillon (6) , Michel Prost (7) , Thibault Moreau (8) , Sofien Ben Ammou (9) , Mohamed Hammami (2) , Gérard Lizard (1)

1 Bio-PeroxIL - Laboratoire Bio-PeroxIL. Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique
2 UM - Université de Monastir - University of Monastir
3 Faculté de médecine de Sousse [Ibn EL Jazzar]
4 UTM - Université de Tunis El Manar
5 LR11IPT08 - Laboratoire des Venins et Biomolécules Thérapeutiques - Laboratory of Venoms and Therapeutic Biomolecules
6 OEil, nutrition et signalisation cellulaire [CSGA]
7 LARA SPIRAL - Laboratoire de Recherche Appliquée Spiral [Bourgogne]
8 Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon)
9 CHU Sahloul - Hôpital Universitaire Sahloul

Lipid peroxidation products, such as 7-ketocholesterol (7KC), may be increased in the body fluids and tissues of patients with neurodegenerative diseases and trigger microglial dysfunction involved in neurodegeneration. It is therefore important to identify synthetic and natural molecules able to impair the toxic effects of 7KC. We determined the impact of 7KC on murine microglial BV-2 cells, especially its ability to trigger mitochondrial and peroxisomal dysfunction, and evaluated the protective effects of α- and γ-tocopherol, Trolox, and oleic acid (OA). Multiple complementary chemical assays, flow cytometric and biochemical methods were used to evaluate the antioxidant and cytoprotective properties of these molecules. According to various complementary assays to estimate antioxidant activity, only α-, and γ-tocopherol, and Trolox had antioxidant properties. However, only α-tocopherol, γ-tocopherol and OA were able to impair 7KC-induced loss of mitochondrial transmembrane potential, which is associated with increased permeability to propidium iodide, an indicator of cell death. In addition, α-and γ-tocopherol, and OA were able to prevent the decrease in Abcd3 protein levels, which allows the measurement of peroxisomal mass, and in mRNA levels of Abcd1 and Abcd2, which encode for two transporters involved in peroxisomal β-oxidation. Thus, 7KC-induced side effects are associated with mitochondrial and peroxisomal dysfunction which can be inversed by natural compounds, thus supporting the hypothesis that the composition of the diet can act on the function of organelles involved in neurodegenerative diseases.

Mots clés: γ-tocopherol; α-tocopherol; peroxisome; murine microglial BV-2 cells; oleic acid; Trolox; mitochondria

Domaines: Neurobiologie

Meryam Debbabi, Thomas Nury, Amira Zarrouk, Nadia Mekahli, Maryem Bezine, et al.. Protective Effects of α-Tocopherol, γ-Tocopherol and Oleic Acid, Three Compounds of Olive Oils, and No Effect of Trolox, on 7-Ketocholesterol-Induced Mitochondrial and Peroxisomal Dysfunction in Microglial BV-2 Cells.. International Journal of Molecular Sciences, 2016, 17 (12), pp.E1973. ⟨10.3390/ijms17121973⟩. ⟨hal-01463786⟩