Figure 1.
Schematic representation of heme oxygenase 1 (HO-1) activity and regulation. HO-1 induction can be regulated at the transcriptional level by several stress-related transcription factors (Nrf2, AP-1, NF-kB, and HIF-1). Two polymorphisms that modify HO-1 inducibility have been indicated. Post-transcriptional regulation can involve miRNA. HO-1 regulates intracellular heme level catalyzing its degradation into biliverdin, carbon monoxide (CO), and ferrous iron (Fe2+). Biliverdin is converted into bilirubin by biliverdin reductase A (BVRA). Free iron activates iron transporters and induces the expression of ferritin. HO-1 metabolic products exert pro-survival activities, as indicated. A truncated form of HO-1, formed by signal peptide peptidase (SSP) cleavage, with nuclear localization and no enzymatic activity, has been described.