Haptoglobin: From hemoglobin scavenging to human health

Masi, Alessandra di; G, De Simone; Ciaccio, Chiara; D’Orso, Silvia; Coletta, Massimo; Ascenzi, Paolo

doi:10.1016/j.mam.2020.100851

Cited by 71 publications

(55 citation statements)

References 431 publications

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“…3). Thus, the loss of ability of the Hp:Hb complexes to bind BZF may reflect: (i) the involvement of residues α 1 Phe36, α 1 Pro95, α 1 Lys99, α 1 Leu100, α 1 His103, β 1 Trp37, and β 1 Asn108 in the Hp1-1:Hb(II)-O 2 complexation [8] and (ii) residues β 2 Trp37, α 2 Pro95, α 2 Ala130, α 2 Thr134, α 2 Thr137, α 2 Tyr140, and α 2 Arg141 do not participate to BZF recognition in tetrameric Hb [48] (Fig. 3).…”

Section: Resultsmentioning

confidence: 99%

“…Haptoglobin (Hp) is a chaperone-like molecule, which binds αβ dimers of plasma Hb, bringing about the formation of a very stable noncovalent complex, which prevents most harmful effects related to the presence of free Hb and/or free heme in the bloodstream, such as (i) heme dissociation from Hb, and (ii) heme oxidation, facilitating the removal of Hb via the reticuloendothelial system and the CD163 receptor-mediated endocytosis by hepatocytes, Kupffer cells, and tissue macrophages [1][2][3][4][5][6][7][8]. Further, Hp binding to αβHb dimers prevents hydrogen-peroxide radical formation and migration, subunit dissociation, globin-cross linking, and heme release, thereby protecting the vascular system from damage by free Hb [8,9].…”

Section: Introductionmentioning

confidence: 99%

“…From a molecular viewpoint, α 1 β 1 (and α 2 β 2 ) dimers (i.e., the products of the tetramer to dimer dissociation of human hemoglobin; Hb) have been always considered to be locked in the high-affinity R conformation (with no "heme-heme" interactions and no Bohr effect) [8,[10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Therefore, ligand binding properties of Hb dimers bound to haptoglobin (Hp) represent an excellent molecular model to study the functional features of pure dimeric species without the interference of the tetrameric population, which is present to a relevant extent even at the lowest affordable concentrations (i.e., 5.0 × 10 − 7 to 1.0 × 10 − 6 M) in the in vitro experiments [24].…”

Section: Introductionmentioning

confidence: 99%

“…We have recently characterized the functional properties of ferrous and ferric Hp:Hb complexes, putting in evidence a marked subunit functional heterogeneity for most of the ligands investigated (namely O 2 and CO for the ferrous form and azide, thiocyanate and imidazole for the ferric form) [8,23,[25][26][27]. However, only in the ferric form we have observed an assembly-linked structural change of ferric Hb upon dimer association to tetramer, as indicated by a much faster dissociation of the sixth axial ligand H 2 O from ferric hemes in Hp:Hb complexes (as well as in isolated subunits) with respect to the tetramer [26,28].…”

Section: Introductionmentioning

confidence: 99%

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Kinetic inequivalence between α and β subunits of ligand dissociation from ferrous nitrosylated human haptoglobin:hemoglobin complexes. A comparison with O2 and CO dissociation

Ascenzi

Pasquadibisceglie

et al. 2021

Journal of Inorganic Biochemistry

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Haptoglobin (Hp) counterbalances the adverse effects of extra-erythrocytic hemoglobin (Hb) by trapping the αβ dimers of Hb in the bloodstream. In turn, the Hp:Hb complexes display Hb-like reactivity. Here, the kinetics of NO dissociation from ferrous nitrosylated Hp:Hb complexes (i.e., Hp1-1:Hb(II)-NO and Hp2-2:Hb(II)-NO, respectively) are reported at pH 7.0 and 20.0 • C. NO dissociation from Hp:Hb(II)-NO complexes has been followed by replacing NO with CO. Denitrosylation kinetics of Hp1-1:Hb(II)-NO and Hp2-2:Hb(II)-NO are biphasic, the relative amplitude of the fast and slow phase being 0.495 ± 0.015 and 0.485 ± 0.025, respectively. Values of k off(NO)1 and k off(NO)2 (i.e., (6.4 ± 0.8) × 10 − 5 s − 1 and (3.6 ± 0.6) × 10 − 5 s − 1 for Hp1-1:Hb(II)-NO and (5.8 ± 0.8) × 10 − 5 s − 1 and (3.1 ± 0.6) × 10 − 5 s − 1 for Hp2-2:Hb(II)-NO) are unaffected by allosteric effectors and correspond to those reported for the α and β subunits of tetrameric Hb(II)-NO and isolated α(II)-NO and β(II)-NO chains, respectively. This highlights the view that the conformation of the Hb α 1 β 1 and α 2 β 2 dimers matches that of the Hb high affinity conformation. Moreover, the observed functional heterogeneity reflects the variation of energy barriers for the ligand detachment and exit pathway(s) associated to the different structural arrangement of the two subunits in the nitrosylated R-state. Noteworthy, the extent of the inequivalence of α and β chains is closely similar for the O 2 , NO and CO dissociation in the R-state, suggesting that it is solely determined by the structural difference between the two subunits.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Kinetic inequivalence between α and β subunits of ligand dissociation from ferrous nitrosylated human haptoglobin:hemoglobin complexes. A comparison with O2 and CO dissociation

Ascenzi

Pasquadibisceglie

et al. 2021

Journal of Inorganic Biochemistry

Self Cite

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“…Hemolysis and hemorrhage are associated with many human pathologies, such as sepsis, brain hemorrhage, atherosclerosis with plaque rupture, sickle cell disease, hemolytic anemias, malaria, diabetic angiopathies, and mechanical injuries. The lysis of red blood cells (RBCs) liberates a large amount of cell-free Hb (Hb) into the bloodstream or tissues that is rapidly scavenged by haptoglobin (Hp) (reviewed by di Masi et al, [17]). Hb-Hp complexes are then taken up by macrophages via their CD163 receptors [18].…”

Section: Hemolysis-and Hemorrhage-driven Damage Mechanismsmentioning

confidence: 99%

Therapeutic Potential of Carbon Monoxide (CO) and Hydrogen Sulfide (H2S) in Hemolytic and Hemorrhagic Vascular Disorders—Interaction between the Heme Oxygenase and H2S-Producing Systems

Gáll

Pethő

Nagy

et al. 2020

IJMS

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Over the past decades, substantial work has established that hemoglobin oxidation and heme release play a pivotal role in hemolytic/hemorrhagic disorders. Recent reports have shown that oxidized hemoglobins, globin-derived peptides, and heme trigger diverse biological responses, such as toll-like receptor 4 activation with inflammatory response, reprogramming of cellular metabolism, differentiation, stress, and even death. Here, we discuss these cellular responses with particular focus on their mechanisms that are linked to the pathological consequences of hemorrhage and hemolysis. In recent years, endogenous gasotransmitters, such as carbon monoxide (CO) and hydrogen sulfide (H2S), have gained a lot of interest in connection with various human pathologies. Thus, many CO and H2S-releasing molecules have been developed and applied in various human disorders, including hemolytic and hemorrhagic diseases. Here, we discuss our current understanding of oxidized hemoglobin and heme-induced cell and tissue damage with particular focus on inflammation, cellular metabolism and differentiation, and endoplasmic reticulum stress in hemolytic/hemorrhagic human diseases, and the potential beneficial role of CO and H2S in these pathologies. More detailed mechanistic insights into the complex pathology of hemolytic/hemorrhagic diseases through heme oxygenase-1/CO as well as H2S pathways would reveal new therapeutic approaches that can be exploited for clinical benefit.

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Epidemiological investigation and proteomic profiling of typical TCM syndrome in HIV/AIDS immunological nonresponders

Zheng

et al. 2022

The Anatomical Record

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HIV/AIDS pandemic remains the world's most severe public health challenge, especially for HIV/AIDS immunological nonresponders (HIV/AIDS‐INRs), who tend to have higher mortality. Due to the advantages in promoting patients' immune reconstitution, Traditional Chinese medicine (TCM) has become one of the mainstays of complementary treatments for HIV/AIDS‐INRs. Given that effective TCM treatments largely depend on precise syndrome differentiation, there is an increasing interest in exploring biological evidence for the classification of TCM syndromes in HIV/AIDS‐INRs. In our study, to identify the typical HIV/AIDS‐INRs syndrome, an epidemiological survey was first conducted in the Liangshan prefecture (China), a high HIV/AIDS prevalence region. The key TCM syndrome, Yang deficiency of spleen and kidney (YDSK), was evaluated by using a tandem mass tag combined with liquid chromatography–tandem mass spectrometry (TMT‐LC–MS/MS). A total of 62 differentially expressed proteins (DEPs) of YDSK syndrome compared with healthy people were screened out. Comparative bioinformatics analyses showed that DEPs in YDSK syndrome were mainly associated with response to wounding and acute inflammatory response in the biological process. The pathway annotation is mainly enriched in complement and coagulation cascades. Finally, the YDSK syndrome‐specific DEPs such as HP and S100A9 were verified by ELISA, and confirmed as potential biomarkers for YDSK syndrome. Our study may lay the biological and scientific basis for the specificity of TCM syndromes in HIV/AIDs‐INRs, and may provide more opportunities for the deep understanding of TCM syndromes and the developing more effective and stable TCM treatment for HIV/AIDS‐INRs.

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Haptoglobin: From hemoglobin scavenging to human health

Cited by 71 publications

References 431 publications

Kinetic inequivalence between α and β subunits of ligand dissociation from ferrous nitrosylated human haptoglobin:hemoglobin complexes. A comparison with O2 and CO dissociation

Kinetic inequivalence between α and β subunits of ligand dissociation from ferrous nitrosylated human haptoglobin:hemoglobin complexes. A comparison with O2 and CO dissociation

Therapeutic Potential of Carbon Monoxide (CO) and Hydrogen Sulfide (H2S) in Hemolytic and Hemorrhagic Vascular Disorders—Interaction between the Heme Oxygenase and H2S-Producing Systems

Epidemiological investigation and proteomic profiling of typical TCM syndrome in HIV/AIDS immunological nonresponders

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