Host: The Japanese Society of Toxicology
Liver lobules have oxygen gradient from 13% (the portal vein) to 1~5% (the central vein). HIF-1alpha is a key transcription factor activated during hypoxia, and ubiquitinated through hydroxylation of proline residues by PHD. Nrf2 is a key factor in defense against oxidative stress and degraded through binding to Keap1. In this study, we investigated the regulation of drug-metabolizing enzymes by treatment of 2,2'-bipyridyl, a PHD inhibitor, or tBHQ, a Keap1 inhibitor, with Hep3B cells. The results of this study suggest that CYP3A family P450s are regulated by hypoxia and oxidative stress.
