Hemopexin: Structure, Function, and Regulation

Abstract

Hemopexin (HPX) is the plasma protein with the highest binding affinity to heme among known proteins. It is mainly expressed in liver, and belongs to acute phase reactants, the synthesis of which is induced after inflammation. Heme is potentially highly toxic because of its ability to intercalate into lipid membrane and to produce hydroxyl radicals. The binding strength between heme and HPX, and the presence of a specific heme-HPX receptor able to catabolize the complex and to induce intracellular antioxidant activities, suggest that hemopexin is the major vehicle for the transportation of heme in the plasma, thus preventing heme-mediated oxidative stress and heme-bound iron loss. In this review, we discuss the experimental data that support this view and show that the most important physiological role of HPX is to act as an antioxidant after blood heme overload, rather than to participate in iron metabolism. Particular attention is also put on the structure of the protein and on its regulation during the acute phase reaction.

Aquisition, Mobilization and Utilization of Cellular Iron and Heme: Endless Findings and Growing Evidence of Tight Regulation

“…Thus, the hemopexin-mediated uptake of heme by the cells has been confused. Finally, hemopexin-deficient mice did not show any impairment of heme metabolism but were sensitive to oxidative stress, as playing a role as anti-oxidants for exogenous insults (Tolosano and Altruda 2002). Along with hemopexin receptors, the presence of heme receptors was reported on the surface of MEL cells, Caco cells and hepatocytes (Uc et al 2004).…”

Heme: a versatile signaling molecule controlling the activities of diverse regulators ranging from transcription factors to MAP kinases

“…Hemopexin, albumin, a-1-microglobulin, and reduced glutathione are the most well-known heme-binding molecules [15,141]. Hemopexin is an intravascular protein that binds free heme with a very high affinity and protects against heme toxicity in vitro [141][142][143]. This protein protects cells without hemopexin receptors by binding heme and preventing the destructive effects of non-specific heme uptake.…”

“…This protein protects cells without hemopexin receptors by binding heme and preventing the destructive effects of non-specific heme uptake. Hemopexin-heme complexes bind hemopexin receptors, which are taken up by the cell via an endocytotic mechanism [142,144]. Heme is then released from hemopexin into the cell and degraded.…”

Modulation of nuclear factor E2-related factor 2–mediated gene expression in mice liver and small intestine by cancer chemopreventive agent curcumin

“…Hemopexin is critical in maintaining the homeostasis of metal ions by forming a complex with heme. As the major vehicle for the transportation of heme, hemopexin could prevent hememediated oxidative stress and heme-bound iron loss (29), functionally analogous to HO-1, which metabolizes heme and prevent oxidative stress. Taken together, our current study suggested that curcumin could coordinately regulate the phase I, II, and III xenobiotic metabolizing enzyme genes as well as antioxidative stress genes through Nrf2-dependent pathways in vivo.…”