Heme oxygenase 1: does it have a role in renal cytoprotection?
Heme oxygenase (HO) was first identified as the rate-limiting enzyme in the degradative pathway of heme, but is now recognized to be involved in diverse biological processes. Different isoforms of HO exist; HO-1 (HMOX1) is ubiquitously present in mammalian tissue with low constitutive expression under physiological conditions, but is upregulated in response to a variety of potentially noxious stimuli. HO-1, an integral component of an important cytoprotective mechanism, mediates its action through removal of heme, the generation of heme breakdown reaction products (biliverdin, free iron, and carbon monoxide), and modulation of key cellular molecules. Data from experimental models in which HO-1 was induced or inhibited, together with observations in genetically modified animals, showed a beneficial effect of HO-1 in several pathways leading to kidney injury. The discovery of a functional guanosine thymine tandem repeat polymorphism in the promoter region of the human HO-1 gene has stimulated clinical investigations in a variety of diseases. However, despite theoretical and experimental support for an important pathophysiological role for HO-1, the relevance of this polymorphism in native kidney or renal transplant function is equivocal. This article reviews the molecular genetics of HO-1, its myriad cytoprotective effects allied to how these are mediated, and relates these findings to experimental and clinical evidence of HO-1 involvement in renal disease.
Courtney
Aisling E
AE
Nephrology Research Group, Queen's University of Belfast, Belfast City Hospital, Belfast BT9 7AB, UK. aecourtney@doctors.org.uk
Maxwell
A Peter
AP
D000818:Animals; D019610:Cytoprotection / Q000502:physiology*; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000166:cytology* / Q000502:physiology*; D016030:Kidney Transplantation
D051547:Heme Oxygenase-1