Various pathologic conditions, such as hemolysis, hemorrhage and cell injury, are characterised by the release of large amounts of heme. Excess of heme may constitute a major treat because heme catalyses the formation of reactive oxygen species, resulting in oxidative stress and, subsequently, cell damage. Protective systems against heme toxicity include the plasma proteins haptoglobin and hemopexin and the cellular enzyme heme oxygenase. Haptoglobin and hemopexin are plasma transporters of hemoglobin and heme, respectively, to the reticulo-endothelial system of the liver and the spleen, where these molecules are catabolised. Both haptoglobin and hemopexin are acute phase proteins, the synthesis of which is induced after hemolysis and inflammatory processes. Heme oxygenase catalyses the rate-limiting step in heme degradation, resulting in the formation of iron, carbon monoxide and biliverdin, which is subsequently converted to bilirubin by biliverdin reductase. Three isoforms of heme oxygenase enzyme have been described: an inducible isoform, heme oxygenase-1, and two constitutively expressed isoforms, heme oxygenase-2 and heme oxygenase-3. Heme oxygenase-1 is induced by a great variety of stimuli other than heme, including oxidative stress, heat shock, UV radiation, ischemia-reperfusion, heavy metals, cytokines and nitric oxide. Generation of animal models, lacking or overexpressing these proteins, has contributed to understanding their role in protection against heme toxicity and to identifying the tissues most sensitive to hemolytic stress. Moreover, these studies have provided evidence that haptoglobin, hemopexin and heme oxygenase-1 are important anti-inflammatory molecules. This review focuses on recent advances in this field.
Protection against heme overload: role of haptoglobin, hemopexin and heme oxygenase-1 as evinced by the analysis of animal models.
Fagoonee S;
2003
Abstract
Various pathologic conditions, such as hemolysis, hemorrhage and cell injury, are characterised by the release of large amounts of heme. Excess of heme may constitute a major treat because heme catalyses the formation of reactive oxygen species, resulting in oxidative stress and, subsequently, cell damage. Protective systems against heme toxicity include the plasma proteins haptoglobin and hemopexin and the cellular enzyme heme oxygenase. Haptoglobin and hemopexin are plasma transporters of hemoglobin and heme, respectively, to the reticulo-endothelial system of the liver and the spleen, where these molecules are catabolised. Both haptoglobin and hemopexin are acute phase proteins, the synthesis of which is induced after hemolysis and inflammatory processes. Heme oxygenase catalyses the rate-limiting step in heme degradation, resulting in the formation of iron, carbon monoxide and biliverdin, which is subsequently converted to bilirubin by biliverdin reductase. Three isoforms of heme oxygenase enzyme have been described: an inducible isoform, heme oxygenase-1, and two constitutively expressed isoforms, heme oxygenase-2 and heme oxygenase-3. Heme oxygenase-1 is induced by a great variety of stimuli other than heme, including oxidative stress, heat shock, UV radiation, ischemia-reperfusion, heavy metals, cytokines and nitric oxide. Generation of animal models, lacking or overexpressing these proteins, has contributed to understanding their role in protection against heme toxicity and to identifying the tissues most sensitive to hemolytic stress. Moreover, these studies have provided evidence that haptoglobin, hemopexin and heme oxygenase-1 are important anti-inflammatory molecules. This review focuses on recent advances in this field.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
