Regulation of redox signalling by an electrophilic cyclic nucleotide

Reactive oxygen species (ROS) have been believed to be toxic substances that induce nonspecific damage in various biological molecules. ROS toxicology is now developing an emerging concept for physiological functions of ROS in the regulation of cell signal transductions. ROS signalling functions and their mechanisms are precisely regulated by several endogenous moderate electrophiles that are themselves generated from ROS during diverse physiological and pathophysiological cellular responses. The chemical biology of electrophiles is an emerging scientific area involving molecular mechanisms that conduct ROS cell signals through receptors to effector molecules at molecular, cellular and organism levels. The formation, signalling and metabolism of 8-nitroguanosine 3′,5′-cyclic monophosphate (8-nitro-cGMP) in cells are probably precisely regulated, and nonselective ROS reactions can be converted into stable, well-controlled electrophilic signal transduction via 8-nitro-cGMP. Modern redox biology is today advancing its frontier of basic research and clinical medicine, including infection, cancer biology, metabolic syndromes, ageing and even stem cell research. As one aspect of this advance, the 8-nitro-cGMP-mediated signalling that may be integrated into cells as a major redox signalling pathway may be a potential target in drug development and may lead to discovery of new therapeutic agents for various diseases.