Heme oxygenase-1: from biology to therapeutic potential

Heme oxygenase-1 (HO-1) is a stress-responsive enzyme that catabolizes free heme into carbon monoxide, iron (which induces the expression of heavy-chain ferritin, an iron-sequestering protein) and biliverdin (which is converted to bilirubin by biliverdin reductase). Over the past few years it has become apparent that these ‘arms’ of the HO-1 system can act protectively in a variety of experimental models of disease; there is also evidence that HO-1 and bilirubin have protective actions in humans. Here, we present a model for the beneficial actions of the products of heme degradation, and we discuss the potential clinical applications of enhancing the HO-1 system. Heme oxygenase-1 (HO-1) is a stress-responsive enzyme that catabolizes free heme into carbon monoxide, iron (which induces the expression of heavy-chain ferritin, an iron-sequestering protein) and biliverdin (which is converted to bilirubin by biliverdin reductase). Over the past few years it has become apparent that these ‘arms’ of the HO-1 system can act protectively in a variety of experimental models of disease; there is also evidence that HO-1 and bilirubin have protective actions in humans. Here, we present a model for the beneficial actions of the products of heme degradation, and we discuss the potential clinical applications of enhancing the HO-1 system. colorless, odorless gas that binds with high affinity to heme groups in the ‘heme pocket’ of some hemoproteins, such as hemoglobin. CO is generated essentially through heme catabolism by heme oxygenase. CO toxicity is caused by its 200-fold higher affinity to the heme groups of hemoglobin, as compared to that of O2. Under physiologic conditions, however, CO is an essential regulatory molecule that controls inflammatory reactions and can be used therapeutically to suppress the deleterious outcome of a variety of experimental inflammatory conditions. guanine thymidine repeats (n). consists of a heterocyclic porphyrin ring surrounding one Fe2+ ion. Heme exists mainly as a prosthetic group of proteins (i.e. hemoproteins), to which it can bind either covalently or noncovalently. Proteins containing non-covalently bound heme groups (e.g. hemoglobin) can release their heme groups and generate free heme. enzyme that in the presence of O2 converts free heme into α-hydroxyhemin, which is then non-catalytically converted into biliverdin and the gas carbon monoxide. any protein containing one or several heme pockets that can incorporate heme as a prosthetic group. tandem repeats of DNA sequences comprising one to six nucleotides. The number of tandem repeats varies from one individual to another (i.e. it is polymorphic).