In Vitro Evaluation of the Effects of 7-Ketocholesterol and 7β-Hydroxycholesterol on the Peroxisomal Status: Prevention of Peroxisomal Damages and Concept of Pexotherapy
摘要
7-Ketocholesterol and 7β-hydroxycholesterol are most often derived from the autoxidation of cholesterol. Their quantities are often increased in the body fluids and/or diseased organs of patients with age-related diseases such as cardiovascular diseases, Alzheimer’s disease, age-related macular degeneration, and sarcopenia which are frequently associated with a rupture of RedOx homeostasis leading to a high oxidative stress contributing to cell and tissue damages. On murine cells from the central nervous system (158N oligodendrocytes, microglial BV-2 cells, and neuronal N2a cells) as well as on C2C12 murine myoblasts, these two oxysterols can induce a mode of cell death which is associated with qualitative, quantitative, and functional modifications of the peroxisome. These changes can be revealed by fluorescence microscopy (apotome, confocal microscopy), transmission electron microscopy, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-qPCR), and gas chromatography-coupled with mass spectrometry (GC-MS). Noteworthy, several natural molecules, including ω3 fatty acids, polyphenols, and α-tocopherol, as well as several Mediterranean oils [argan and olive oils, Milk-thistle (Sylibum marianum) and Pistacia lenticus seed oils], have cytoprotective properties and attenuate 7-ketocholesterol- and 7β-hydroxycholesterol-induced peroxisomal modifications. These observations led to the concept of pexotherapy.