Figure 4.

Therapeutic targeting of free heme. Free heme, and its pathophysiological effects, might be targeted directly and indirectly, extra- and intracellularly, by a range of mechanisms. Extracellularly, albumin and the two naturally occurring acute phase proteins, Hp and Hx, can scavenge cell-free Hb and free heme, respectively, whereas CO can prevent the release of heme from Hb. Intracellularly, induction of HO-1 or FtH, might target excess heme and labile Fe, respectively. Antioxidants such as BR and the heme carrier protein PRX1, could prevent the participation of heme-Fe in the generation of unfettered production of free radicals (ROS). Specific heme transport between the intra- and extracellular compartments, including Abcg2, FLVCR, HCP1 and HRG-1, might be considered as potential, therapeutic targets to afford protection against heme cytotoxicity. Abbreviations: Bcrp/Abcg2, breast cancer resistance protein/ATP-binding cassette g2; BR, bilirubin; CO, carbon monoxide; Fe, iron; FLVCR, feline leukemic virus receptor; FtH, ferritin; Hb, hemoglobin; HCP1, heme carrier protein-1; Hp, haptoglobin; HO-1, heme oxygenase-1; HRG-1, heme responsive gene-1; Hx, hemopexin; ROS, reactive oxygen species.