FIG. 4.

H₂S and the phase II cytoprotective pathways. Under basal conditions, Kelch-like ECH-associated protein 1 (Keap1) binds to nuclear factor erythroid 2-related factor 2 (Nrf2) and sequesters it, leading to its ubiquitination by cullin 3 (Cul3). When H₂S levels increase in the cell in response to stress, Keap1 is sulfhydrated, leading to the dissociation of Nrf2. Nrf2 translocates to the nucleus and activates the transcription of target genes harboring the antioxidant response element (ARE) in association with coactivator proteins such as Maf.