Bioactive Lipids and Redox Signaling: Molecular Mechanism and Disease Pathogenesis.

The actions of bioactive lipids and reactive oxygen species (ROS) are usually coupled, and their interplay is a common and important mechanism mediating tissue injury, inflammation, and other pathologies. Understanding the interplay of ROS and lipid mediators will extend horizons for researchers to clarify the pathogenesis of different diseases and help identify therapeutic targets for treatment of these diseases. Some bioactive lipids are converted into oxidized lipids during cell or tissue oxidative stress such as isoprostanes and isoketals, which are even more bioactive than their precursors. Moreover, many enzymes that produce lipid mediators such as prostaglandin H synthases, lipoxygenases, and cytochrome P450 isoforms may catalyze the production of ROS. Bioactive lipids-lysophospholipids, sphingolipids, or deposited lipids in cells-are shown to stimulate redox enzymes to produce ROS. In addition, a lipid-channel-ROS axis in different organelles may be associated with the crosstalk of ROS and bioactive lipids. This Forum focuses on the crosstalk of ROS with sphingolipids, P450 eicosanoids, lysophospholipids, and deposited plasma lipids and related novel signaling pathway in their reciprocal actions, which is expected to provide novel insights into the pathogenesis of different diseases associated with the participation of these lipid mediators. It is imperative to further understand the molecular mechanism mediating the crosstalk of ROS with specific lipid mediators and to develop more effective therapeutic strategies to target the interplay of ROS and lipid mediators for treatment specific to different organ diseases. Antioxid. Redox Signal. 28, 911-915.