Heme Oxygenase as a Shock Protein

Heme oxygenase (HO : EC 1.14.99.3) is a key enzyme for heme catabolism and catalyzes the oxidative degradation of heme to form biliverdin IXa, an immediate precursor of bilirubin. The HO activity can be induced by treatment with hemin, the substrate itself, as well as with various other non-heme stress inducers. Recently, it has been shown that HO is a major 32 kDa stress protein inducible by treatments with heavy metals, heat shock, or acute phase inducers. The induction of HO is considered to be a member of the defense system against environmental hazards, because bilirubin is one of the antioxidants. Among two isozymes of HO, i.e., HO-1 and HO-2, only HO-1 is inducible. In the present article, therefore, we described the molecular mechanisms of HO-1 gene activation by environmental hazards. We also discussed the HO-1 gene regulation during differentiation of erythrocytes and monocytes.