Reactive Oxygen Species as Signaling Molecules

Summary

Although the pathophysiological role of reactive oxygen species (ROS) has received considerable attention, there is a growing realization that oxidants also can play a normal, physiological role within cells. These observations came from studies initially using cultured cells stimulated by a variety of peptide growth factors. In this context, several groups were able to show that after ligand addition, the subsequent production of ROS was a necessary component of downstream signaling. Subsequent experiments have defined the enzymatic source of ligand activated ROS production and some of the relevant molecular targets. Here, we review these observations and discuss the role of ROS in normal growth factor signaling. In addition, we describe how these observations are currently being extended to the production of ROS emanating from the mitochondria, and how mitochondrial ROS also might be involved in certain signaling events. We also discuss how ROS might be involved in the induction of cellular senescence by acting as important intracellular mediators. Finally, we review the role of ROS in stem cells and how oxidants might again act to regulate the biology of these critical cells. Together, it is hoped that these observations will serve as a framework to more fully understand how ROS participate in aging. In particular, these observations provide the starting point to determine whether ROS participate in aging as random, stochastic damaging agents, or whether they function as mediators of critical redox-dependent pathways.