EXPRESSION OF THE MESSENGER-RNA OF HEME-BINDING PROTEIN-23 IS COORDINATED WITH THAT OF HEME OXYGENASE-1 BY HEME AND HEAVY-METALS IN PRIMARYRAT HEPATOCYTES AND HEPATOMA-CELLS

A 23-kDa protein with high affinity for heme (K-D = 55 nM), therefore termed heme-binding protein 23 kDa (HBP23), was purified from rat live r cytosol [Iwahara, S., et al. (1995) Biochemistry 34, 13398-13406], H omology search of the cloned HBP23 cDNA revealed that this protein bel ongs to a recently recognized class of thiol peroxidases, the antioxid ant peroxiredoxin family. Since HBP23 gene expression was highest in t he liver, HBP23 mRNA regulation by heme and heavy metals was investiga ted in cultures of primary rat hepatocytes and mouse hepatoma Hepa 1-6 cells. In both cell cultures HBP23 mRNA levels were upregulated in a time- and dose-dependent manner by heme. Heme-dependent induction of H BP23 mRNA occurred coordinately with that of the heme-metabolizing enz yme heme oxygenase-1, which was recently identified as inducible by ox idative stress. Treatment of primary rat hepatocyte or hepatoma cell c ultures with the heavy metals CdCl2 (10 mu M) and CoCl2 (300 mu M) ind uced in parallel HBP23 and HO-1 mRNA levels, in the case of CdCl2 to e ven higher levels than heme. By contrast, mRNA expression of another h eme binding protein, hemopexin, was not induced in hepatocyte cell cul tures by heme or heavy metals. The data suggest that the expression of HBP23 and HO-1 mRNA is regulated by (a) similar mechanism(s) in liver and that both genes could play a common physiological role as antioxi dants and/or in heme metabolism.