Defense Against Oxidative Tissue Injury: The Essential Role Played by Heme Oxygenase-1

Oxidative stresses provoke a set of special cellular responses, particularly those which participate in the defense against tissue injuries. Free heme, which can be rapidly released from hemeproteins, may constitute a major threat in the oxidant stress because it catalyzes the formation of reactive oxygen species (ROS). To counteract such insults, cells respond by inducing the 33-kDA heat shock protein, heme oxygenase (HO) -1, the rate-limiting enzyme in heme degradation. Induced HO-1 as such removes free heme by an enzymatic process. In addition, HO-1 induction itself confers protection to tissues from further oxidative injuries. Consistent with this concept, the abrogation of HO-1 induction, or chemical ablation of HO activity abolishes the beneficial effect of HO-1, and results in the aggravation of tissue injuries. In this article, we review recent advances on the essential role of HO-1 in tissue protection in various models of experimental oxidative tissue injuries and in human disorders, with special emphasis on the role of its induction in tissue defense and the consequences of its inhibition on tissue injuries.