Roles Nrf2 Plays in Myeloid Cells and Related Disorders
Figure 2
Nrf2 activation by inflammation-related molecules. Inflammation stimulates the production/accumulation of Nrf2-inducing molecules. Nrf2 inducers modify target reactive cysteine residues of Keap1; blue arrows indicate the flow of various Nrf2 inducers toward the reactive cysteine residues of Keap1. Inflammation induces COX-2, which leads to the production of 15d-PGJ2 and PGA2. COX-2 also produces electrophilic derivatives from ω3-fatty acids. PGA2, 15d-PGJ2, and ω3-fatty acid derivatives inactivate Keap1, leading to Nrf2 activation. Inflammation also induces iNOS and causes NO production. NO and its derivatives 8-nitro-cGMP and OA-NO2 also modify Keap1 and activate Nrf2. PGA2, 15d-PGJ2, ω3-fatty acid derivatives, and OA-NO2 preferentially modify Cys273/288 of Keap1, whereas NO preferentially modifies Cys151, and 8-nitro-cGMP preferentially modifies Cys434.
