Attenuation of 7-ketocholesterol- and 7β-hydroxycholesterol-induced oxiapoptophagy by nutrients, synthetic molecules and oils: Potential for the prevention of age-related diseases

7-Ketocholesterol: Effects on viral infections and hypothetical contribution in COVID-19

“…The biosynthesis and the metabolism of 7-ketocholesterol (7KC) are described in the detail by Wang et al [ 23 ], Brahmi et al [ 72 ], Vejux et al [ 14 ] and Griffiths et al [ 24 ]. For detailed information on the biosynthesis and degradation of 7KC and 7β-hydroxycholesterol, please see the review from Nury T et al [ 112 ]. …”

“…Indeed, there are several data that favour the pro-oxidative and pro-inflammatory activities of 7KC that may be associated with a type of death defined as oxiapoptophagy (OXIdative stress + APOPTOsis + autoPHAGY), due to the ability of 7KC (at high concentration) to induce oxidative stress and an apoptotic mode of cell death associated with autophagy criteria [ 14 , 72 , 73 ]. In several cells from different types and from different species, i) oxidative stress is characterized by ROS overproduction including at the mitochondrial level, protein carbonylation, lipid peroxidation and decrease and/or enhancement of anti-oxidant enzymes (catalase, superoxide dismutases (SODs), glutathione peroxidase (GPx), ii) apoptosis is associated by an activation of the mitochondrial pathway leading to a loss of transmembrane mitochondrial potential (ΔΨm), an externalization of phosphatidylserine, an increase of plasma membrane rigidity associated with an increased cell permeability contributing to an altered packing of the lipid bilayer, a cytoplasmic release of cytochrome c, a caspase cascade activation (caspases-3,-7,-8 and -9), poly-ADP ribose (PARP) fragmentation and an internucleosomal DNA fragmentation associated with condensation and/or fragmentation of the nuclei and iii) autophagy is characterized by the presence the presence of autophagosomes and autophagolysosomes revealed by transmission electron microscopy as well as activation of LC3-I into LC3-II [ 73 , 74 ]. In addition, 7KC-induced oxiapoptophagy is associated with a production of inflammatory cytokines (IL-1β, IL-8) [ 72 , 14 ].…”

Impact of Oxysterols on Cell Death, Proliferation, and Differentiation Induction: Current Status

“…The relationship between phospholipolysis and cell toxicity is not totally understood, but phospholipolysis might be part of a cell death process involving caspase activation, leading cells to apoptosis [ 54 ]. Phospholipidosis, characterized by the presence of “myelin figures” in large vacuoles, could correspond to reticulophagy [ 96 ].…”

Antioxidant Properties and Cytoprotective Effect of Pistacia lentiscus L. Seed Oil against 7β-Hydroxycholesterol-Induced Toxicity in C2C12 Myoblasts: Reduction in Oxidative Stress, Mitochondrial and Peroxisomal Dysfunctions and Attenuation of Cell Death

“…The stock solutions of 7β-OHC was prepared at 800 µg/mL (2 mM), as previously described by Ragot et al [67], and stored in the dark at 4 • C. A stock solution of PLSO was prepared at 80 mg/mL in dimethyl sulfoxide (DMSO; Sigma-Aldrich) and stored in the dark at 4 • C. An α-tocopherol (the major component of vitamin E; Sigma-Aldrich) solution was prepared to 80 mM in absolute ethanol, as previously described [60], and stored in the dark at 4 • C. For the different experiments, C2C12 myoblasts were used at 80% confluency; they were seeded either into Petri dishes of 10 cm in diameter (1.2 × 10 6 cells per Petri dish), in six-well plates (2 × 10 5 cells per well), or in 96-well plates (10 × 10 4 cells per well). After 12 h, the growth medium was removed and the C2C12 cells were incubated with 7β-OHC (20 µg/mL/50 µM) for 24 h with or without PLSO (100 µg/mL), or α-tocopherol (400 µM) (used as a positive control for cytoprotection) [28]. PLSO and α-tocopherol were introduced in the culture medium 2 h before 7β-OHC.…”

“…In the presence of oxidative stress, glucose and cholesterol can undergo auto-oxidation by a free-radical mechanism. The cholesterol oxide derivatives (oxysterols) formed by cholesterol auto-oxidation in oxidative stress conditions mainly correspond to those that are oxidized at position C7 (7-ketocholesterol (7KC) and 7β-hydroxycholesterol (7β-OHC)) [ 25 , 26 , 27 , 28 ]. Interestingly, 7KC and 7β-OHC have similar cytotoxic effects (although the induction of cell death is faster with 7β-OHC) and these two oxysterols can be interconverted: the enzyme 11β-hydroxysteroid dehydrogenase-1 (11β-HSD1) converts 7KC into 7β-OHC, whereas 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2) converts 7β-OHC into 7KC [ 29 , 30 ].…”