Figure 2.

Mechanism of Nrf2 regulation in the treatment of renal I/R. In physiological condition Nrf2 binds to Kelch-like ECH-associated protein-1 (Keap1) in the cytoplasm and is degraded by ubiquitin-proteasome pathway. During renal I/R the hyperactivation of Nrf2 by CDDO, H₂S, water-soluble H₂S donor (such as GYY4137) leads to nuclear traslocation of Nrf2 that binds to antioxidant response elements and activates transcription of the genes encoding proteins involved in antioxidants mechanisms and iron metabolism thereby preventing the ROS-mediated tubular damage and the ferroptotic cascade.