Heme Oxygenase-1: A Novel Therapeutic Target in Oxidative Tissue Injuries

Oxidative stresses such as oxidant stimuli, inflammation, exposure to xenobiotics, or ionizing irradiation provoke cellular protective responses, principally involving transcriptional activation of genes encoding proteins which participate in the defense against oxidative tissue injuries. Excess of free heme, which is released from hemeproteins under such conditions, may constitute a major threat because it can catalyze the formation of reactive oxygen species (ROS). Exposure of mammalian cells to oxidative stimuli induces heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, as well as a 33-kDa heat shock protein. In various model systems, HO-1 induction confers protection on tissues from further injuries, while the abrogation of its induction accelerates cellular injuries. In this article, we review recent advances in the regulatory mechanism of ho-1 gene expression and the role of HO-1 in various models of experimental oxidative tissue injuries, and its potential therapeutic implications.