Figure 1.

Under normal conditions, Keap1 homodimerizes and forms Keap1-Cul3-E3 ligase complex, which facilitates Nrf2 ubiquitination and degradation. During I/R injury, Nrf2 is released from this complex and translocates into the nucleus without and binds with ARE to trigger the transcription of endogenous protective genes. Additionally, during this condition, PI3K, JNK, and PKC activate Nrf2 via phosphorylation, whereas GSK-3β inhibits Nrf2 activation through Fyn kinase activation. (ARE: Antioxidant Response Element, Keap1: Kelch-like ECH-associated protein 1, GSK3β: Glycogen synthase kinase-3β Nrf2: Nuclear factor (erythroid-derived 2)-related factor 2, P: phosphate, PI3K: Phosphoinositide 3-kinase, UbE2: Ubiquitin-conjugated E2 enzyme).