The interaction of human serum albumin and hemopexin with porphyrins

Morgan, William T.; Smith, Ann; Koskelo, Pentti

doi:10.1016/0005-2795(80)90246-9

Cited by 98 publications

(89 citation statements)

References 25 publications

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“…Albumin is supposed to be the most important protoporphyrin carrier in the plasma (23). With the concentrations used in the present study, which simulate those in plasma, albumin has a greater binding capacity for protoporphyrin than has the erythrocyte membrane (Fig.…”

Section: Discussionmentioning

confidence: 99%

Light-induced protoporphyrin release from erythrocytes in erythropoietic protoporphyria.

Sandberg¹,

Brun²

1982

J. Clin. Invest.

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A B S T R A C T The photohemolysis of normal erythrocytes incubated with protoporphyrin is reduced in the presence of albumin. When globin is added to normal erythrocytes loaded with protoporphyrin, protoporphyrin is bound to globin. During irradiation protoporphyrin moves from globin to the erythrocyte membrane and photohemolysis is initiated.Erythrocytes in patients with erythropoietic protoporphyria contain large amounts of protoporphyrin bound to hemoglobin. Upon irradiation of these cells in the absence of albumin, 40% of protoporphyrin and 80% of hemoglobin is released after 240 kJ/m2. The released protoporphyrin is hemoglobin bound. In contrast, when albumin is present only 8% of hemoglobin is released whereas protoporphyrin is released to 76%. The released protoporphyrin is albumin bound.A hypothesis for the release of erythrocyte protoporphyrin in erythropoietic protoporphyria without simultaneous hemolysis is proposed: Upon irradiation protoporphyrin photodamages its binding sites on hemoglobin, moves through the plasma membrane, and is bound to albumin in plasma.

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Section: Discussionmentioning

confidence: 99%

Light-induced protoporphyrin release from erythrocytes in erythropoietic protoporphyria.

Sandberg¹,

Brun²

1982

J. Clin. Invest.

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“…The extracellular presence of hemopexin, which binds these porphyrins with relatively low affinity (K d ϳ 1 M) (36, 37), did not improve the export efficiency compared with albumin (data not shown), which binds these porphyrins with similarly low affinity (K d ϳ 1 M) (37).…”

Section: Heme Export Depends On the Avidity And Concentration Ofmentioning

confidence: 98%

Kinetics and Specificity of Feline Leukemia Virus Subgroup C Receptor (FLVCR) Export Function and Its Dependence on Hemopexin

Yang

Philips

Doty

et al. 2010

Journal of Biological Chemistry

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The feline leukemia virus subgroup C receptor (FLVCR) is a heme export protein that is required for proerythroblast survival and facilitates macrophage heme iron recycling. However, its mechanism of heme export and substrate specificity are uncharacterized. Using [55 Fe]heme and the fluorescent heme analog zinc mesoporphyrin, we investigated whether export by FLVCR depends on the availability and avidity of extracellular heme-binding proteins. Export was 100-fold more efficient when the medium contained hemopexin (K d < 1 pM) compared with albumin (K d ‫؍‬ 5 nM) at the same concentration and was not detectable when the medium lacked heme-binding proteins. Besides heme, FLVCR could export other cyclic planar porphyrins, such as protoporphyrin IX and coproporphyrin. However, FLVCR has a narrow substrate range because unconjugated bilirubin, the primary breakdown product of heme, was not transported. As neither protoporphyrin IX nor coproporphyrin export improved with extracellular hemopexin (versus albumin), our observations further suggest that hemopexin, an abundant protein with a serum concentration (6.7-25 M) equivalent to that of the iron transport protein transferrin (22-31 M), by accepting heme from FLVCR and targeting it to the liver, might regulate macrophage heme export and heme iron recycling in vivo. Final studies show that hemopexin directly interacts with FLVCR, which also helps explain why FLVCR, in contrast to some major facilitator superfamily members, does not function as a bidirectional gradient-dependent transporter. Together, these data argue that hemopexin has a role in assuring systemic iron balance during homeostasis in addition to its established role as a scavenger during internal bleeding or hemolysis.The biological roles of heme are diverse and encompass most areas of cell metabolism and gene regulation. Heme serves as a prosthetic group in the hemeproteins, which are involved in crucial biological functions, including oxygen binding (hemoglobin and myoglobin), oxygen metabolism (oxidases, peroxidases, catalases, and hydroxylases), electron transfer (cytochromes) (4), and signal transduction (nitric-oxide synthases) (5). In addition, heme serves as a signaling molecule in erythropoiesis and other physiological systems. Because heme generally signals by binding and inactivating a transcriptional repressor (e.g. Bach1) or translational inhibitor (e.g. heme-regulated inhibitor and thus eIF␣2 kinase), its impact is immediate (6 -8). Perhaps for this reason, heme is utilized in time-sensitive processes, such as the regulation of circadian rhythm (9), N-end rule pathway/protein ubiquitination (10), and globin synthesis. Heme is also required for microRNA processing (11). However, excess free or non-protein-bound heme damages lipid, protein, and DNA through the generation of reactive oxygen species, resulting in cellular injury and death (12). Therefore, free cellular heme levels must be tightly regulated to provide an adequate supply yet avoid heme toxicities (4,(13)(14)(15).Most studies of h...

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“…tation of 35 S-PrP-sen were performed as described previously (3) except that a 1-h pulse and no chase was used for the labeling. PcTS-Fe 3ϩ was maintained at 10 M in the labeling media of all but the control cells.…”

Section: Methodsmentioning

confidence: 99%

“…PrP-res was purified from the brains of hamsters infected with 263K strain as described previously (27). Preparation of 35 S-labeled hamster PrP-sen was carried out as described (28). The PrP-sen used here was the recombinant PrP-sen that lacks a glycophosphatidylinositol anchor because of the introduction of a stop codon at hamster PrP codon 231 (29).…”

Section: Methodsmentioning

confidence: 99%

Inhibition of protease-resistant prion protein formation by porphyrins and phthalocyanines

Caughey

Raymond²,

Horiuchi³

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

225

205

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A central aspect of pathogenesis in the transmissible spongiform encephalopathies or prion diseases is the conversion of normal protease-sensitive prion protein (PrPsen) to the abnormal protease-resistant form, PrP-res. Here we identify porphyrins and phthalocyanines as inhibitors of PrP-res accumulation. The most potent of these tetrapyrroles had IC 50 values of 0.5-1 M in scrapie-infected mouse neuroblastoma (ScNB) cell cultures. Inhibition was observed without effects on protein biosynthesis in general or PrP-sen biosynthesis in particular. Tetrapyrroles also inhibited PrPres formation in a cell-free reaction composed predominantly of hamster PrP-res and PrP-sen. Inhibitors were found among phthalocyanines, deuteroporphyrins IX, and meso-substituted porphines; examples included compounds containing anionic, neutral protic, and cationic peripheral substituents and various metals. We conclude that certain tetrapyrroles specifically inhibit the conversion of PrP-sen to PrP-res without apparent cytotoxic effects. The inhibition observed in the cell-free conversion reaction suggests that the mechanism involved direct interactions of the tetrapyrrole with PrP-res and͞or PrP-sen. These findings introduce a new class of inhibitors of PrP-res formation that represents a potential source of therapeutic agents for transmissible spongiform encephalopathies.

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The interaction of human serum albumin and hemopexin with porphyrins

Cited by 98 publications

References 25 publications

Light-induced protoporphyrin release from erythrocytes in erythropoietic protoporphyria.

Light-induced protoporphyrin release from erythrocytes in erythropoietic protoporphyria.

Kinetics and Specificity of Feline Leukemia Virus Subgroup C Receptor (FLVCR) Export Function and Its Dependence on Hemopexin

Inhibition of protease-resistant prion protein formation by porphyrins and phthalocyanines

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