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

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

  • Free Radic Res. 2019 May;53(5):535-561. doi: 10.1080/10715762.2019.1612891.
Randa Sghaier 1 2 3 4,  Amira Zarrouk 2 3 5 6,  Thomas Nury 1,  Ilham Badreddine 1 7 8,  Nora O'Brien 5,  John J Mackrill 6,  Anne Vejux 1,  Mohammad Samadi 9,  Boubker Nasser 8,  Claudio Caccia 10,  Valerio Leoni 11,  Thibault Moreau 1 12,  Mustapha Cherkaoui-Malki 1,  Ahmed Salhedine Masmoudi 4,  Gérard Lizard 1
Affiliations

Affiliations

  • 1 University Bourgogne Franche-Comté/Inserm , Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' , Dijon , France.
  • 2 Laboratory of Biochemistry, Faculty of Medicine , University Sousse , Sousse , Tunisia.
  • 3 Faculty of Medicine, Laboratory - NAFS "Nutrition - Functional Food & Vascular Health" , Monastir & University Sousse , Sousse , Tunisia.
  • 4 Laboratory of Biotechnology and Valorisation of Bio-Géo Ressources , University Manouba, Higher Institute of Biotechnology , Sidi Thabet , Tunisia.
  • 5 School of Food and Nutritional Sciences , University College Cork , Cork , Ireland.
  • 6 Department of Physiology , Biosciences Institute, University College Cork , Cork , Ireland.
  • 7 University Ibn Zohr, Lab. 'Valorisation des Ressources Naturelles et Environnement' , Taroudant , Morocco.
  • 8 Laboratory Neuroscience and Biochemistry , University Hassan 1er , Settat , Morocco.
  • 9 Department of Chemistry , University Lorraine, Metz Technopôle , Metz , France.
  • 10 Laboratory of Medical Genetics and Neurogenetics , Foundation IRCCS Istituto Neurologico Carlo Besta , Milan , Italy.
  • 11 Laboratory of Clinical Chemistry , Hospital of Varese, ASST-Settelaghi , Milan , Italy.
  • 12 Department of Neurology , University Hospital , Dijon , France.
PMID: 31039616 DOI: 10.1080/10715762.2019.1612891
Abstract

Mitochondrial dysfunction and oxidative stress are involved in neurodegenerative diseases associated with an enhancement of lipid peroxidation products such as 7β-hydroxycholesterol (7β-OHC). It is, therefore, important to study the ability of 7β-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 7β-OHC (50 µM) with or without biotin (10 and 100 nM) or α-tocopherol (positive control of cytoprotection). The effects of biotin on 7β-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 7β-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 O2•- 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.

Keywords

158N oligodendrocytes; 7β-hydroxycholesterol; apoptosis; autophagy; biotin; lipid metabolism; mitochondria; oxiapoptophagy; oxidative stress.

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