HPPE is a specific nonelectrophilic and physiological Bach1 inhibitor via heme-binding sites of Bach1 protein, derepresses Bach1-mediated repression.
HPPE induces up-regulation of Hmox1 mRNA is mediated by Bach1 inhibition in vivo.
Nuclear export of Bach1 is required for HPPE-mediated Bach1 derepression, HPPE has an additional activity in Nrf2 stabilization besides Bach1 inhibition.
Pre- and posttreatment of HPPE is neuroprotective against acute MPTP neurotoxicity.
HPPE significantly reduced MPTP-induced increases in TNF-α and Mcp-1 mRNA levels, HPPE significantly increased mRNA levels of Nrf2 compared to MPTP-treated mice that received the vehicle.
Bach1 is a known transcriptional repressor of the Nrf2 pathway.
Bach1 ablation is cytoprotective, as it suppresses reactive oxygen species (ROS) generation, mitigates excessive inflammation, improves mitochondrial function, and inhibits apoptosis.