Regulation of heme oxygenase-1 by redox signals involving nitric oxide

Heme oxygenase-1 (HO-1) is an inducible stress protein the expression of which can be markedly augmented in eukaryotes by a wide range of substances that cause a transient change in the cellular redox state. The importance of this protein in physiology and disease is underlined by the versatility of HO-1 inducers and the functional role attributed to HO-1 products (carbon monoxide and bilirubin) in conditions that are associated with moderate or severe cellular stress. An intriguing aspect is the recent evidence showing that nitric oxide, a ubiquitous signaling molecule, finely modulates the activation of HO-1 expression. As the effects of oxidative stress on the regulation of the HO-1 gene have been well established and characterized, this review will focus on the biological relevance of redox signals involving nitric oxide and reactive nitrogen species that lead to up-regulation of the HO-1 pathway, with particular emphasis on vascular tissues and the cardiovascular system.