Heme Oxygenase Is a Stress Protein

Abnormal elevation of HO activity in response to metals and other xenobiotics has both negative and positive consequences for cells. While the physiological role of HO involves the turnover of heme compounds, a protracted increase in the de novo synthesis of HO has been generally associated with perturbation of cellular processes which may lead to cell injury or death. Reduction of heme via HO can deplete cytochrome P-450 levels, inhibit mixed function oxidase activities, and deplete mitochondrial respiratory cytochromes (Maines and Kappas 1977). Cellular respiration and biotransformation of endogenous compounds and xenobiotics may become compromised. 

Early in vivo studies examining the effect of metals on HO demonstrated that metal induction of HO is tissue specific with respect to the inducing metal. Most of these studies examined HO induction by assaying enzymatic activity. Cadmium, mercury, lead, chromium, manganese, iron, cobalt, nickel, copper, tin, indium, thallium, platinum, silver, and selenium have been shown to induce HO in liver (Maines and Kappas 1977 Woods et al. 1979, 1984 Eaton et al. 1980) however, cobalt and cadmium are the most effective inducers. In contrast, nickel, tin, and platinum represent the best inducers of the enzyme in kidney in heart, mercury is the most effective. While the usual response of HO to metals is induction of synthesis and 

Based on the evidence presented above, HO can be classified as a stress protein. To date, it is the only stress protein covered in this review which possesses enzymatic activity. In a manner similar to other well-known stress proteins, HO induction is dependent on the type of stressor, tissue, and species. Further research efforts should focus on the role of HO as a player in cellular defense mechanisms against injury by stressors. 

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