Oxysterols and mechanisms of apoptotic signaling: implications in the pathology of degenerative diseases

Oxysterols, or cholesterol oxidation products, are oxygenated derivatives of cholesterol which are formed endogenously during the biosynthesis of bile acids and steroid hormones. In addition, oxysterols may also be absorbed from the diet as they are found in many commonly consumed foods. Oxysterols have been shown to possess many potent and diverse biological activities, and the study of the effects of these oxidation products on the human body forms a wide field of research. The results of most research efforts support the conclusion that certain oxysterols, predominantly those found in oxidized low-density lipoprotein, exert pathological effects such as the induction of apoptotic cell death. Moreover, apoptosis induced by oxysterols has been strongly implicated in the pathogenesis of atherosclerosis as well as a variety of other diseases. The study of oxysterol-induced apoptosis is an emerging area, and the following review aims to provide a detailed account on the chronology of events involved. Current evidence of the involvement of the death receptor pathway and protein kinases is examined as well as important apoptosis regulators such as the mitochondria, B-cell lymphoma-2 proteins and caspases. The effect of oxysterols on gene expression, protein interactions and membrane properties are also discussed.