RTA-408 Protects Kidney from Ischemia-Reperfusion Injury in Mice via Activating Nrf2 and Downstream GSH Biosynthesis Gene

Figure 9

Schematic showing how RTA-408 activates the Nrf2 antioxidant system to protect against renal ischemia-reperfusion injury. Outburst of ROS production during which the I/R damages the lipid and protein in renal tubular cells. RTA-408 is capable of increasing the Nrf2 nucleus translocation and subsequently upregulating of downstream antioxidant genes, including GSH biosynthesis gene GCLc, to protect the kidney against IRI. Cys: cysteine; Gly: glycine; Glu: glutamic acid; γGC: γ-glutamylcysteine; GSH: glutathione; Xc⁻: membrane glutamate-cystine transporter; GCLc: glutamate-cysteine ligase catalytic subunit; GCLm: glutamate-cysteine ligase modulate subunit; GSS: glutathione synthetase; GST: glutathione S-transferase; GSR: glutathione reductase; HO-1: heme oxygenase 1; NQO-1: NAD(P)H dehydrogenase 1; ARE: antioxidant response element; MDA: malondialdehyde.