title: Effects of cholesterol oxides on cell death induction and calcium increase in human neuronal cells (SK-N-BE) and evaluation of the protective effects of docosahexaenoic acid (DHA; C22:6 n-3).
abstract: Some oxysterols are associated with neurodegenerative diseases. Their lipotoxicity is characterized by an oxidative stress and induction of apoptosis. To evaluate the capacity of these molecules to trigger cellular modifications involved in neurodegeneration, human neuronal cells SK-N-BE were treated with 7-ketocholesterol, 7α- and 7β-hydroxycholesterol, 6α- and 6β-hydroxycholesterol, 4α- and 4β-hydroxycholesterol, 24(S)-hydroxycholesterol and 27-hydroxycholesterol (50-100μM, 24h) without or with docosahexaenoic acid (50μM). The effects of these compounds on mitochondrial activity, cell growth, production of reactive oxygen species (ROS) and superoxide anions (O2(-)), catalase and superoxide dismutase activities were determined. The ability of the oxysterols to induce increases in Ca(2+) was measured after 10min and 24h of treatment using fura-2 videomicroscopy and Von Kossa staining, respectively. Cholesterol, 7-ketocholesterol, 7β-hydroxycholesterol, and 24(S)-hydroxycholesterol (100μM) induced mitochondrial dysfunction, cell growth inhibition, ROS overproduction and cell death. A slight increase in the percentage of cells with condensed and/or fragmented nuclei, characteristic of apoptotic cells, was detected. With 27-hydroxycholesterol, a marked increase of O2(-) was observed. Increases in intracellular Ca(2+) were only found with 7-ketocholesterol, 7β-hydroxycholesterol, 24(S)-hydroxycholesterol and 27-hydroxycholesterol. Pre-treatment with docosahexaenoic acid showed some protective effects depending on the oxysterol considered. According to the present data, 7-ketocholesterol, 7β-hydroxycholesterol, 24(S)-hydroxycholesterol and 27-hydroxycholesterol could favor neurodegeneration by their abilities to induce mitochondrial dysfunctions, oxidative stress and/or cell death associated or not with increases in cytosolic calcium levels.
authors: Team 'Biochemistry of Peroxisome, Inflammation and Lipid Metabolism' EA 7270, University of Bourgogne - Franche Comté, INSERM, Dijon, France; University of Monastir, Faculté de Médecine, LR12ES05, Lab-NAFS 'Nutrition - Functional Food & Vascular Health', Monastir, Tunisia; School of Food and Nutritional Sciences, University College Cork, Cork, Ireland; Department of Physiology, University College Cork, BioSciences Institute, College Road, Cork, Ireland. Electronic address: zarroukamira@gmail.com.
authors: Amira
authors: A
authors: Zarrouk
authors: Team 'Biochemistry of Peroxisome, Inflammation and Lipid Metabolism' EA 7270, University of Bourgogne - Franche Comté, INSERM, Dijon, France.
authors: Thomas
authors: T
authors: Nury
authors: LCPMC-A2, ICPM, Département de Chimie, University of Lorraine, Metz, France.
authors: Mohammad
authors: M
authors: Samadi
authors: School of Food and Nutritional Sciences, University College Cork, Cork, Ireland.
authors: Yvonne
authors: Y
authors: O'Callaghan
authors: University of Monastir, Faculté de Médecine, LR12ES05, Lab-NAFS 'Nutrition - Functional Food & Vascular Health', Monastir, Tunisia.
authors: Mohamed
authors: M
authors: Hammami
authors: School of Food and Nutritional Sciences, University College Cork, Cork, Ireland.
authors: Nora M
authors: NM
authors: O'Brien
authors: Team 'Biochemistry of Peroxisome, Inflammation and Lipid Metabolism' EA 7270, University of Bourgogne - Franche Comté, INSERM, Dijon, France.
authors: Gérard
authors: G
authors: Lizard
authors: Department of Physiology, University College Cork, BioSciences Institute, College Road, Cork, Ireland.
authors: John J
authors: JJ
authors: Mackrill
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002784:Cholesterol / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010087:Oxides / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D018696:Neuroprotective Agents; D010087:Oxides; D013481:Superoxides; D004281:Docosahexaenoic Acids; D002784:Cholesterol; D013482:Superoxide Dismutase; D002118:Calcium
keywords: Calcium; Cell death; Oxidative stress; Oxysterols; SK-N-BE