Transfer of Heme from Ferrihemoglobin and Ferrihemoglobin Isolated Chains to Hemopexin

Hrkal, Zbyněk; Vodrážka, Z.; Kalousek, Ivan

doi:10.1111/j.1432-1033.1974.tb03386.x

Cited by 216 publications

(159 citation statements)

References 18 publications

Supporting

Mentioning

150

Contrasting

Order By: Relevance

“…These are hemopexin (Hxp), a naturally occurring heme scavenger in plasma and a double mutant (H64Y/V86F) apomyoglobin (ApoMb), which avidly binds heme released from Hb. The affinity constant value for the binding of heme to the single binding center of hemopexin molecule was estimated to be 1.9 × 10 14 m −1 11, whereas the affinity of apomyoglobin for heme was reported to be 8 × 10 13 m −1 12. In spite of these differences among these two heme receptors, we consistently showed in this report that ferric looses heme more readily than the ferryl form of Hb.…”

mentioning

confidence: 50%

See 1 more Smart Citation

Differential heme release from various hemoglobin redox states and the upregulation of cellular heme oxygenase‐1

et al. 2016

View full text Add to dashboard Cite

Despite advances in our understanding of the oxidative pathways mediated by free hemoglobin (Hb), the precise contribution of its highly reactive redox forms to tissue and organ toxicities remains ambiguous. Heme, a key degradation byproduct of Hb oxidation, has recently been recognized as a damage‐associated molecular pattern (DAMP) molecule, able to trigger inflammatory responses. Equally damaging is the interaction of the highly redox active forms of Hb with other biological molecules. We determined the kinetics of heme loss from individual Hb redox states—ferrous (Fe2+), ferric (Fe3+), and ferryl (Fe4+)—using two different heme receptor proteins: hemopexin (Hxp), a naturally occurring heme scavenger in plasma, and a double mutant (H64Y/V86F), apomyoglobin (ApoMb), which avidly binds heme released from Hb. We show for the first time that ferric Hb (Fe3+) loses heme at rates substantially higher than that of ferryl Hb (Fe4+). This was also supported by a higher expression of heme oxygenase‐1 (HO‐1) when ferric Hb was added to cultured lung alveolar epithelial cells (E10). The reported cytotoxicity of Hb may therefore be attributed to a combination of accelerated heme loss from the ferric form and protein radical formation associated with ferryl Hb. Targeted therapeutic interventions can therefore be designed to curb specific oxidative pathways of Hb in hemolytic anemias and when Hb is used as an oxygen‐carrying therapeutic.

show abstract

mentioning

confidence: 50%

“…Final concentration of Hb in heme equivalents was 2 μ m and the final concentration of 20 μ m of H64Y/V86F was used. For heme transfer to Hpx we followed early reported procedures with minor modifications 11, 20. Sodium phosphate buffer (100 m m , pH 7.0) was used for the Hpx experiments.…”

Section: Methodsmentioning

confidence: 99%

Differential heme release from various hemoglobin redox states and the upregulation of cellular heme oxygenase‐1

et al. 2016

View full text Add to dashboard Cite

show abstract

“…However, free heme is highly toxic and can be released at the site of injury by heme proteins including Mb, enzymes such as the cytochromes or catalase, or by oxidation of Hb. In these scenarios, the circulating acute phase protein, hemopexin (Hx) binds to heme and serves as a means for its clearance (68,70,78). In 2005, Hvidberg and colleagues identified the low-density lipoprotein (LDL) receptor-related protein, CD91, as the hemopexin complexed with heme (Hx:heme) complex receptor (70).…”

Section: Role Of Ho-1 In the Mononuclear Phagocyte Systemmentioning

confidence: 99%

The Mononuclear Phagocyte System in Homeostasis and Disease: A Role for Heme Oxygenase-1

Hull

Agarwal

George

2014

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

Significance: Heme oxygenase-1 (HO-1) is a potential therapeutic target in many diseases, especially those mediated by oxidative stress and inflammation. HO-1 expression appears to regulate the homeostatic activity and distribution of mononuclear phagocytes ( MP) in lymphoid tissue under physiological conditions. It also regulates the ability of MP to modulate the inflammatory response to tissue injury. Recent Advances: The induction of HO-1 within MP-particularly macrophages and dendritic cells-modulates the effector functions that they acquire after activation. These effector functions include cytokine production, surface receptor expression, maturation state, and polarization toward a pro-or anti-inflammatory phenotype. The importance of HO-1 in MP is emphasized by their expression of specific receptors that primarily function to ingest heme-containing substrate and deliver it to HO-1. Critical Issues: MP are the first immunological responders to tissue damage. They critically affect the outcome of injury to many organ systems, yet few therapies are currently available to specifically target MP during disease pathogenesis. Elucidation of the role of HO-1 expression in MP may help to direct broadly applicable therapies to clinical use that are based on the immunomodulatory capabilities of HO-1. Future Directions: Unraveling the complexities of HO-1 expression specifically within MP will more completely define how HO-1 provides cytoprotection in vivo. The use of models in which HO-1 expression is specifically modulated in bone marrow-derived cells will allow for a more complete characterization of its immunoregulatory properties.

show abstract

“…The calculated saturation functions of the strong binding sites correspond well with the experiments at low concentration of erythrosin. The calculations were performed by the curve-fitting method with a computer EAI 640 as previously described [5].…”

Section: Equilibrium Dialysismentioning

confidence: 99%

The Interaction of Human Hemoglobin with Erythrosin

Kalousek¹,

Jandová²,

Vodrážka³

1978

European Journal of Biochemistry

Self Cite

View full text Add to dashboard Cite

The interactions of erythrosin with deoxyhemoglobin, oxyhemoglobin, carbonmonoxyhemoglobin, methemoglobin, cyanomethemoglobin and hemoglobin α and β chains have been studied by using the equilibrium dialysis, the difference and circular dichroic (CD) spectra and stopped‐flow method. The values of equilibrium and kinetic parameters, as well as CD characteristics, show that in addition to a number of weak binding sites hemoglobin contain four, relatively strong binding sites, one per chain. The properties of the strong binding sites depend on the ligand of the heme group and the charge of the heme group is not directly responsible for this fact. Consequently the properties of deoxyhemoglobin and methemoglobin, differing from the mutually close properties of the other derivatives, confirm that the state of the heme group affects the conformation of hemoglobin molecules in solution. These results are in a good agreement with the classification established on the heme iron spin state.

show abstract

Transfer of Heme from Ferrihemoglobin and Ferrihemoglobin Isolated Chains to Hemopexin

Cited by 216 publications

References 18 publications

Differential heme release from various hemoglobin redox states and the upregulation of cellular heme oxygenase‐1

Differential heme release from various hemoglobin redox states and the upregulation of cellular heme oxygenase‐1

The Mononuclear Phagocyte System in Homeostasis and Disease: A Role for Heme Oxygenase-1

The Interaction of Human Hemoglobin with Erythrosin

Contact Info

Product

Resources

About