Figure 5.
The proposed mechanism of the regulation of NO of cell migration through redox regulation of SERCA2b in normal and high glucose. In normal glucose, NO released from exogenous NO donor or from iNOS induced by IL-1β induces the reversible S-glutathiolation of SERCA, predominantly on the most reactive thiol on cysteine 674, which increases SERCA activity and intracellular calcium uptake into SR/ER, decreases calcium influx, and inhibits cell migration. High glucose interrupts this cascade by the oxidation of the reactive thiol on SERCA cysteine 674, blocks the NO-induced S-glutathiolation of SERCA, and abolishes the inhibitory effect of NO on cell migration.