Lipid droplets dependent or independent cytoprotective activities of unsaturated fatty acids, Lorenzo’s oil and sulfo-N-succinimidyl oleate on 7-ketocholesterol-induced oxidative stress, organelle dysfunction and cell death on 158N and ARPE-19 cells: Cell targets and benefits of sulfo-N-succinimidyl oleate

Abstract

7-ketocholesterol is a cytotoxic oxysterol which is frequently increased in many chronic inflammatory and age-related diseases. Thus, the inhibition of the toxicity of 7-ketocholesterol is a major challenge to treat these diseases. 158N oligodendrocytes were used to evaluate the cytoprotective effects of lipids: ω-3 and ω-9 fatty acids (α-linolenic acid (C18:3n-3), eicosapentaenoic acid (C20:5n-3), docosahexaenoic acid (C22:6n-3), erucic acid (C22:1n-9) and oleic acid (C18:1n-9)), Lorenzo's oil (a mixture of oleic and erucic acid, 4:1) and sulfo-N-succinimidyl oleate (SSO, a synthetic derivative of oleic acid). On 158N cells, the ability of these molecules to inhibit 7KC-induced oxiapoptophagy (plasma membrane alteration, loss of ΔΨm, peroxisomal dysfunction, reactive oxygen species overproduction, induction of apoptosis and autophagy) were determined. ARPE-19 epithelial retinal cells were also used to evaluate the cytoprotective effect of SSO on 7KC-induced cell death. Unlike ω-3 and ω-9 fatty acids and Lorenzo's oil, sulfo-N-succinimidyl oleate had no cytotoxic effects over a wide range of concentrations. Noteworthy, unlike fatty acids and Lorenzo's oil, the cytoprotective effects of sulfo-N-succinimidyl oleate on 7KC-induced oxiapoptophagy, a caspase-dependent mode of cell death on 158N cells, were not associated with an accumulation of lipid droplets. In addition, on ARPE-19 cells, sulfo-N-succinimidyl oleate prevented 7KC-induced oxidative stress and cell death. These different characteristics of SSO make it possible to envisage its use for therapeutic purposes in diseases where 7-ketocholesterol levels are increased without eventual secondary side effects due to lipid droplets formation.