Figure 4.

Redox regulation of SERCA by reactive oxygen/nitrogen species. RNS produced by •NO and O₂^−• increase glutathione adducts (GSS-) of cysteine(C)-674 of SERCA. This increases Ca²⁺ uptake into sarcoplasmic reticulum stores, inhibiting store-dependent Ca²⁺ influx, and decreasing cytosolic Ca²⁺ which causes vasodilation, inhibits smooth muscle cell (SMC) migration, and increases endothelial cell (EC) migration. Under pathophysiological conditions higher levels of ROS increase the destruction and consumption of •NO, producing RNS which can oxidize the SERCA C674 thiol (−SO₃H), preventing its reversible S-glutathiolation and blocking the stimulation of SERCA by •NO. Thus, the redox status of C674 can determine physiological and pathophysiological changes in vascular tone and cell migration. From reference 8.