Ceramide: a novel player in reactive oxygen species-induced signaling?

Generation of ceramide in the plasma membrane, with the subsequent formation of large ceramide-enriched membrane platforms, serves signal transduction via receptors, but also nonreceptor-mediated activation of cells. Recent studies demonstrate that enzymes mediating release of reactive oxygen species (ROS) localize to membrane rafts, and the integrity of these rafts is required for cellular ROS release. The authors and others noted that in a feed-forward mechanism, ROS are able to stimulate ceramide-releasing enzymes, for instance, acid sphingomyelinase, resulting in the formation of ceramide-enriched membrane platforms that may mediate cellular activation initiated by oxidative stress.