title: Hemeoxygenase-1 and renal ischaemia-reperfusion injury.
abstract: Degradation by the inducible enzyme hemeoxygenase-1 (HO-1) is the principal route of mammalian heme metabolism. The resultant generation of free iron, carbon monoxide and biliverdin results in myriad actions including promoting cell survival, circulatory integrity and immunomodulation. This review examines the evidence from both human studies and work performed in experimental models implicating the intrinsic heme-HO-1 pathway as important in determining both the susceptibility and severity of acute kidney injury. Additional work using chemical inducers of HO-1 has demonstrated the efficacy of strategies to upregulate enzyme activity in ameliorating the severity of experimental ischaemia-reperfusion injury whilst genetic ablation of HO-1 or pharmacological inhibition of HO-1 activity results in an augmented injury phenotype. There remain a multitude of candidate pathways to account for the therapeutic efficacy of HO-1 induction. Although this may reflect a truly multifactorial mechanism of action, the identification of the relative contribution of key components such as carbon monoxide generation remains critical to allow the rational design of agents for translational application in human disease.
authors.affiliation: MRC Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, UK. david.ferenbach@ed.ac.uk
authors.forename: David A
authors.initials: DA
authors.lastname: Ferenbach
authors.forename: David C
authors.initials: DC
authors.lastname: Kluth
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hughes
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001664:Biliverdine / Q000378:metabolism; D002248:Carbon Monoxide / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000201:enzymology / Q000276:immunology; D015427:Reperfusion Injury / Q000201:enzymology*; D015854:Up-Regulation
chemical_list: D002248:Carbon Monoxide; D051547:Heme Oxygenase-1; D001664:Biliverdine