Comparison of the effects of major fatty acids present in the Mediterranean diet (oleic acid, docosahexaenoic acid) and in hydrogenated oils (elaidic acid) on 7-ketocholesterol-induced oxiapoptophagy in microglial BV-2 cells
2017
Debbabi, Meryam | Zarrouk, Amira | Bezine, Maryem | Meddeb, Wiem | Nury, Thomas | Badreddine, Asmaa | Karym, El Mostafa | Sghaier, Randa | Brétillon, Lionel | Guyot, Stéphane | Samadi, Mohammad | Cherkaoui-Malki, Mustapha | Nasser, Boubker | Mejri, Mondher | Ben-Hammou, Sofien | Hammami, Mohamed | Lizard, Gérard | Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] (BIO-PEROXIL) ; Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bourgogne Franche-Comté [COMUE] (UBFC) | جامعة سوسة = Université de Sousse = University of Sousse (USO) | Laboratoire des Venins et Toxines, Institut Pasteur de Tunis ; Institut Pasteur de Tunis ; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur) | Faculté des Sciences de Bizerte [Université de Carthage] ; Université de Carthage (Tunisie) = University of Carthage (UCAR) | Université Hassan 1er [Settat] | Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA) ; Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS) | Procédés Microbiologiques et Biotechnologiques (PMB) ; Procédés Alimentaires et Microbiologiques (PAM) ; Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Procédés Alimentaires et Microbiologiques [Dijon] (PAM) ; Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC) | Laboratoire de Chimie et Physique - Approche Multi-échelle des Milieux Complexes (LCP-A2MC) ; Université de Lorraine (UL) | جامعة المنستير - Université de Monastir - University of Monastir (UM) | Univ. Bourgogne (Dijon, France) Univ. Monastir (Monastir, Tunisia) Univ. El Manar (Tunis, Tunisia) Univ. Bizerte (Bizerte, Tunisie) ASSAD (Louhans, France) Department of Neurology Action Integree of the Comite Mixte Inter-universitaire Franco-Marocain (CMIFM) from the PHC Volubulis/Toubkal program, Ministere des Affaires Etrangeres AIMA/10/238 Conseil Regional de Bourgogne
International audience
Show more [+] Less [-]English. Increased levels of 7-ketocholesterol (7KC), which results mainly from cholesterol auto-oxidation, are often found in the plasma and/or cerebrospinal fluid of patients with neurodegenerative diseases and might contribute to activation of microglial cells involved in neurodegeneration. As major cellular dysfunctions are induced by 7KC, it is important to identify molecules able to impair its side effects. Since consumption of olive and argan oils, and fish is important in the Mediterranean diet, the aim of the study was to determine the ability of oleic acid (OA), a major compound of olive and argan oil, and docosahexaenoic acid (DHA) present in fatty fishes, such as sardines, to attenuate 7KC-induced cytotoxic effects. Since elaidic acid (EA), the trans isomer of OA, can be found in hydrogenated cooking oils and fried foods, its effects on 7KC-induced cytotoxicity were also determined. In murine microglial BV-2 cells, 7KC induces cell growth inhibition, mitochondrial dysfunctions, reactive oxygen species overproduction and lipid peroxidation, increased plasma membrane permeability and fluidity, nuclei condensation and/or fragmentation and caspase-3 activation, which are apoptotic characteristics, and an increased LC3-II/LC3-I ratio, which is a criterion of autophagy. 7KC is therefore a potent inducer of oxiapoptophagy (OXIdation + APOPTOsis + autoPHAGY) on BV-2 cells. OA and EA, but not DHA, also favor the accumulation of lipid droplets revealed with Masson's trichrome, Oil Red O, and Nile Red staining. The cytotoxicity of 7KC was strongly attenuated by OA and DHA. Protective effects were also observed with EA. However, 7KC-induced caspase-3 activation was less attenuated with EA. Different effects of OA and EA on autophagy were also observed. In addition, EA (but not OA) increased plasma membrane fluidity, and only OA (but not EA) was able to prevent the 7KC-induced increase in plasma membrane fluidity. Thus, in BV-2 microglial cells, the principal fatty acids of the Mediterranean diet (OA, DHA) were able to attenuate the major toxic effects of 7KC, thus reinforcing the interest of natural compounds present in the Mediterranean diet to prevent the development of neurodegenerative diseases.
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