Effects of cholesterol oxides on cell death induction and calcium increase

摘要: 32 Some oxysterols are associated with neurodegenerative diseases. Their lipotoxicity is characterized by an 33 oxidative stress and induction of apoptosis. To evaluate the capacity of these molecules to trigger cellular 34 modifications involved in neurodegeneration, human neuronal cells SK-N-BE were treated with 7-keto-35 cholesterol, 7a-and 7b-hydroxycholesterol, 6a-and 6b-hydroxycholesterol, 4a-and 4b-hydroxycholes-36 terol, 24 (S)-hydroxycholesterol and 27-hydroxycholesterol (50–100 lM, 24 h) without or with 37 docosahexaenoic acid (50 lM). The effects of these compounds on mitochondrial activity, cell growth, 38 production of reactive oxygen species (ROS) and superoxide anions (O2 À), catalase and superoxide dismu-39 tase activities were determined. The ability of the oxysterols to induce increases in Ca2+ was measured 40 after 10 min and 24 h of treatment using fura-2 videomicroscopy and Von Kossa staining, respectively. 41 Cholesterol, 7-ketocholesterol, 7b-hydroxycholesterol, and 24 (S)-hydroxycholesterol (100 lM) induced 42 mitochondrial dysfunction, cell growth inhibition, ROS overproduction and cell death. A slight increase 43 in the percentage of cells with condensed and/or fragmented nuclei, characteristic of apoptotic cells, 44 was detected. With 27-hydroxycholesterol, a marked increase of O2 À was observed. Increases in intracel-45 lular Ca2+ were only found with 7-ketocholesterol, 7b-hydroxycholesterol, 24 (S)-hydroxycholesterol and 46 27-hydroxycholesterol. Pre-treatment with docosahexaenoic acid showed some protective effects 47 depending on the oxysterol considered. According to the present data …