Activation of stress signaling pathways by electrophilic oxidized and nitrated lipids

Unsaturated fatty acids are prone to radical reactions that occur in biological situations where extensive formation of reactive oxygen and nitrogen species (ROS and RNS) takes place. These reactions are frequent in inflammatory conditions such as atherosclerosis, and yield a variety of biologically active species, many of which are electrophilic in nature. Electrophilic lipid oxidation and nitration products can influence redox cell signaling via S-alkylation of protein thiols, and moderate exposure to these species evokes protective cell signaling responses through this mechanism. Herein, we review the stress signaling pathways elicited by electrophiles derived from unsaturated fatty acids, focusing on the Keap1-Nrf2 pathway, the heat shock response pathway (HSR), and the unfolded protein response pathway (UPR).

► Electrophilic lipid oxidation and nitration products influence redox cell signaling via S-alkylation of protein thiols.
► Moderate exposure to electrophilic species evoke protective signaling responses.
► These include the Keap1-Nrf2 pathway, the heat shock response (HSR), and the unfolded protein response (UPR) that are reviewed herein.