Gene regulation of HBP 23 by metalloporphyrins and protoporphyrin IX in liver and hepatocyte cultures

Heme-binding protein 23 kDa (HBP23) belongs to the antioxidant family of peroxiredoxins and binds heme with high affinity, In vivo treatment of rats with heme induced expression of HBP23 mRNA levels in liver coordinately with that of the heme degrading enzyme heme oxygenase-1 (HO-1). In primary rat hepatocyte cultures Sn-, Co-, and Zn-metalloprotoporphyrin as well as the heme precursor protoporphyrin IX increased the HBP23 mRNA expression to a level similar to that elicited by heme, Heme-dependent induction of HBP23 mRNA was prevented by pretreatment with actinomycin D, indicating a transcriptional mechanism of gene induction, The results suggest that the coordinate gene regulation pattern of HBP23 and HO-1 plays a physiological role against oxidative stress. (C) 1997 Academic Press.