Heme oxygenase-1 as a protective gene.

Heme oxygenases catalyze the rate-limiting step in heme degradation, resulting in the formation of carbon monoxide, iron and biliverdin that is subsequently reduced to bilirubin by biliverdin reductase. The products of this enzymatic reaction have important biological effects, including antioxidant, anti-inflammatory and cytoprotective functions. Three isoforms of heme oxygenase (HO) have been described: two constitutively expressed isoforms, HO-2 and HO-3, and an inducible isoform, HO-1 that is increased as an adaptive response to several injurious stimuli including heme, hyperoxia, hypoxia, endotoxin and heavy metals. Induction of HO-1 has been implicated in numerous clinically relevant disease states including transplant rejection, hypertension, atherosclerosis, lung injury, endotoxic shock and others. This review will focus on the protective functions of HO-1.