FIG. 1.

Simplified scheme of the relationship between the GSH redox potential and biological cellular status. Redox potential, E_hc, for the glutathione disulfide–glutathione couple (GSSG/2GSH), is an important indicator of the intracellular redox environment that reflects cellular status. E_hc (GSSG/2GSH) has the most negative value for proliferating cells, including cancer cells, and is more positive for differentiated cells. A number of oxidative stress-related pathologies, for example, inflammation, are characterized by further increase in GSH redox potential and are often associated with GSH depletion. If E_hc (GSSG/2GSH) becomes too positive, then apoptotic redox signals are initiated, resulting in the removal of cells that have lost an ability to control their redox environment. Very high values of the E_hc leave only necrosis or necroptosis as a path to cell death. Adapted from Schafer and Buettner (63) with permission of Elsevier, Inc.