Depleted uranium (DU) is a by-product from the chemical enrichment of naturally occurring uranium. Natural uranium isInterest in depleted uranium (DU) is rapidly increasing as researchers realize its many potential military and civilian applications. Uranium, a naturally occurring heavy metal, is found in all soils, waters and rocks. Natural uranium is comprised of three radioactive isotopes: 238 U, 235 U, and 234 U. Of these, 235

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Hemopexin (HPX) has two principal roles: it sequesters free heme in vivo for the purpose of preventing the toxic effects of this moiety, which is largely due to heme's ability to catalyze free radical formation, and it transports heme intracellularly thus limiting its availability as an iron source for pathogens. Spectroelectrochemistry was used to determine the redox potential for heme and meso-heme (mH) when bound by HPX. At pH 7.2, the heme-HPX assembly exhibits E (1/2) values in the range 45-90 mV and the mH-HPX assembly in the range 5-55 mV, depending on environmental electrolyte identity. The E (1/2) value exhibits a 100 mV positive shift with a change in pH from 7.2 to 5.5 for mH-HPX, suggesting a single proton dependent equilibrium. The E (1/2) values for heme-HPX are more positive in the presence of NaCl than KCl indicating that Na(+), as well as low pH (5.5) stabilizes ferro-heme-HPX. Furthermore, comparing KCl with K(2)HPO(4), the chloride salt containing system has a lower potential, indicating that heme-HPX is easier to oxidize. These physical properties related to ferri-/ferro-heme reduction are both structurally and biologically relevant for heme release from HPX for transport and regulation of heme oxygenase expression. Consistent with this, when the acidification of endosomes is prevented by bafilomycin then heme oxygenase-1 induction by heme-HPX no longer occurs.