Vejux, A.; Malvitte, L.; Lizard, G. Side effects of oxysterols: cytotoxicity, oxidation, inflammation, and phospholipidosis. Braz J Med Biol Res 2008; 41: 545-556.

Figure 2. Signaling pathways associated with 7-ketocholesterol- and 7β-hydroxycholesterol-induced apoptosis. 7-Ketocholesterol- and 7β-hydroxycholesterol-induced cell death are characterized by an early externalization of phosphatidylserine and by the following events: Ca²⁺ influx; activation of calmodulin and calcineurin leading to Bad dephosphorylation and subsequent mitochondrial depolarization (loss of transmembrane mitochondrial potential ΔΨm); mitochondrial release of cytochrome c, apoptosis-inducing factor (AIF) and endonuclease-G (Endo-G) into the cytosol; caspase-3, -7, -8, and -9 activation; Bid truncation; poly(ADP-ribose)polymerase (PARP) degradation; cleavage of the DNA fragmentation factor (DFF45)/inhibitor of caspase-activated DNase (ICAD), leading to the activation of caspase-activated DNase (CAD) involved in internucleosomal DNA fragmentation. The ability of 7-ketocholesterol and 7β-hydroxycholesterol to induce an overproduction of reactive oxygen species (ROS) contributes to decrease the transmembrane mitochondrial potential (ΔΨm) and the intracellular level of reduced glutathione (GSH). In addition, 7-ketocholesterol inhibits the PDK1/Akt (PKB) signaling pathway, and both 7-ketocholesterol and 7β-hydroxycholesterol trigger the formation of multilamellar cytoplasmic structures (myelin figures) containing high levels of phospholipids. (Copyright Dr. Gérard Lizard, Inserm, France).