Thiols in cellular redox signalling and control.
Reactive oxygen (ROS) and reactive nitrogen species (RNS) produced in vivo at levels that cannot be dealt with adequately by endogenous antioxidant systems can lead to the damage of lipids, proteins, carbohydrates and nucleic acids. Oxidative modification of these molecules by toxic levels of ROS and RNS represents an extreme event that can lead to deleterious consequences such as loss of function. More recently, however, interest has focused on the formation of these species at sub-toxic levels and their potential to act as biological signal molecules. Subtoxic ROS and RNS production can lead to alterations in cellular and extracellular redox state, and it is such alterations that have been shown to signal changes in cell functions. By the use of a variety of cell types it has been shown that numerous cellular processes including gene expression can be regulated by subtle changes in redox balance Examples of this include the activation of certain nuclear transcription factors, and the determination of cellular fate by apoptosis or necrosis. Cellular redox balance is, under normal circumstances, probably under genetic control and maintained by an array of enzymatic systems that ensure that overall reducing conditions prevail. Thiols, by virtue of their ability to be reversibly oxidised, are recognised as key components involved in the maintenance of redox balance. Additionally, increasing evidence suggests that thiol groups located on various molecules act as redox sensitive switches thereby providing a common trigger for a variety of ROS and RNS mediated signalling events. In this review we discuss a number of cellular processes in which ROS and RNS have been implicated in redox signalling mechanisms. Particular attention has been paid to the importance of thiols and thiol-containing molecules in these processes.