[11] Redox potential of GSH/GSSG couple: Assay and biological significance

Redox-signaling mechanisms function in cell regulation and growth control. Agents altering glutathione (GSH) concentration affect the transcription of detoxification enzymes, cell proliferation, and apoptosis. GSH, GSH S-conjugates, and its disulfide form (GSSG), or the redox state of the GSH/GSSG couple provide a mechanistic control or signal for functional changes. A loss or oxidation of GSH occurs in association with differentiation both in vitro and in vivo and during apoptosis. In contrast, increases in GSH and/or a reduction of the GSH/GSSG pool is associated with growth stimulation by nutrients and growth factors. Thus, the balance of GSH and GSSG may not only reflect oxidative stress but may reflect changes in redox signaling and control. The most widely used indicator of the redox state of the GSH pool is the ratio of GSH to GSSG. The cellular balance of GSH and GSSG provides a dynamic indicator of oxidative stress. Although GSH is synthesized continuously and has various fates in cells, these rates are generally slow relative to the turnover by the oxidation-reduction cycle. The activity of the GSSG reductase is dependent on GSSG concentration. During acute oxidative stress, GSH concentration decreases and the associated increase in GSSG concentration results in an increased turnover of the GSH/GSSG cycle.