Protective and Detrimental Role of Heme Oxygenase-1

Abstract

Heme oxygenase (HO) is the enzyme that catalyzes the regioselective oxidative catabolism of heme, with the simultaneous release of carbon monoxide (CO), ferrous iron (Fe2+), and biliverdin, which is then reduced to bilirubin. The first consequence of this enzymatic activity is a cyto-protective effect in various stress-related conditions. Two main isoforms of heme oxygenase are present in humans: HO-1, inducible, and HO-2, constitutive. HO-1 may be induced in many organs and tissues by a variety of stimuli, such as the same substrate heme, heat shock, ROS and stressful conditions. Therefore, its critical role is cell protection against such insults. HO-1 may be both up- and down-regulated. During the past decade, a large number of studies have been carried out to delineate the diverse roles of HO-1 in inflammatory, neurodegenerative and other stress conditions. Due to its cyto-protective effects, HO-1 up-regulation may be useful in many stress-related diseases. On the contrary, HO-1 over-expression may contribute to tissue injury under certain unfavorable conditions such as neurodegeneration and carcinogenesis. Therefore, HO-1 inhibition mediated by natural or synthetic compounds may be useful.