The role of some lipids and their metabolites in programmed cell death (lipoapoptosis)

In recent years, the understanding of the mechanisms involved in the regulation of lipoapoptosis signaling pathways has expanded considerably. However, many mechanisms of apoptosis induction by lipids as well as molecules mediating intracellular and systemic signals belonging to AOS/enzyme-dependent phospholipid metabolites are not completely clear. This review summarizes the current understanding of the mechanisms of apoptotic cell death induction by some lipid molecules. Literature search was performed in the database “PubMed”, “eLIBRARY” using key words: “apoptosis”, “lipids”, “fatty acids”, “eicosanoids”, “reactive oxygen species”. A brief characterization of the signaling pathways of apoptosis is given. The role of reactive oxygen species and their dependent products of lipid peroxidation in the regulation of the main signaling pathways of apoptosis are shown. Particular attention is paid to the product of phospholipid metabolism – 4-hydroxynonenal. Pro- and anti-apoptotic effects of some prostaglandins are demonstrated. Arguments are presented that prostaglandins of series J and D are pro-apoptotic in most cells, and this effect depends on activation of the prostanoid receptor DP2 and on reduction of AKT kinase activity. In contrast, the E-series prostaglandins and hydroxyecosatetraenoic acid act opposite to the J-series and D-series prostaglandins, reducing apoptosis by activating AKT and increasing Bcl-2 protein expression. The role of individual fatty acids involved in the initiation and transduction of pro-apoptotic and anti-apoptotic signals is assessed. It was shown that saturated fatty acids have the maximum damaging potential than their unsaturated counterparts. An in-depth understanding and deciphering of the mechanisms by which lipids and their metabolites modulate the activation of signaling pathways of programmed cell death can help to develop therapeutic strategies to prevent a number of diseases associated with impaired regulation of apoptosis.