Redox clamp model for study of extracellular thiols and disulfides in redox signaling

Extracellular thiol/disulfide redox environments are highly regulated in healthy individuals and become oxidized in disease. This oxidation affects the function of cell surface receptors, ion channels, and structural proteins. Downstream signaling due to changes in extracellular redox potential can be studied using a redox clamp in which thiol and disulfide concentrations are varied to obtain a series of controlled redox potentials. Previous applications of this approach show that cell proliferation, apoptosis, and proinflammatory signaling respond to extracellular redox potential. Furthermore, gene expression and proteomic studies reveal the global nature of redox effects, and different cell types, for example, endothelial cells, fibroblasts, monocytes, and epithelial cells, show cell-specific redox responses. Application of the redox clamp to studies of different signaling pathways could enhance the understanding of redox transitions in many aspects of normal physiology and disease.