Heme-based catalytic properties of human serum albumin

Ascenzi, Paolo; Masi, Alessandra di; Fanali, Gabriella; Fasano, Mauro

doi:10.1038/cddiscovery.2015.25

Cited by 66 publications

(57 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, some researchers had found that some variations in the V-shaped cavity of SAs from mammals, apes, reptiles, amphibians, and fish could be associated with the FA1 binding site for heme, bilirubin, fatty acids, and various exogenous compounds. 9 , 10 In contrast, PR has been shown to bind to Sudlow’s site II, which is located at some distance from the FA1 site (IB) and in the different subdomain (IIIA) of SA. 5 , 8 On the other hand, the pharmacokinetics and pharmacodynamics (PK/PD) analysis of PR was conducted mainly in animals, including mice, rats, dogs, and so forth, which might impose big difficulties when comparing these data with those of clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Novel Approach for Characterizing Propofol Binding Affinities to Serum Albumins from Different Species

Shityakov

Fischer

et al. 2020

ACS Omega

View full text Add to dashboard Cite

The interaction between the main carrier (serum albumin, SA) of endogenous and exogenous compounds in the bloodstream of different species (human, bovine, canine, rat, rabbit, and sheep) and a general anesthetic agent (propofol, PR) was investigated using an experimental technique (high-performance liquid chromatography) and computational methods (molecular docking, molecular dynamics, sequence, and phylogenetic analyses). The obtained results revealed the differences in the PR binding affinity to various homologous forms of this protein with reliable statistics ( R 2 = 0.9 and p -value < 0.005), correlating with the evolutionary relationships among SAs from different species. Additionally, the protein conformational changes (root-mean-square deviation ≈ 1.0 Å) and amino acid conservation of binding sites in protein domains were detected, contributing to the SA–PR binding modes. Overall, the outcomes from this study might provide a novel methodology to assess protein–ligand interactions and to gain some interesting insights into drug pharmacokinetics and pharmacodynamics to explain its variations among different species.

show abstract

Section: Introductionmentioning

confidence: 99%

Novel Approach for Characterizing Propofol Binding Affinities to Serum Albumins from Different Species

Shityakov

Fischer

et al. 2020

ACS Omega

View full text Add to dashboard Cite

show abstract

“…Each study week, two of the eight animals were randomized as described above, desensitized, and then administered either intravenous human Hp (2‐1 and 2‐2) plasma fraction concentrates (800 mg/kg total dose, in two divided 100 mg/kg bolus doses at 4 and 7 h after bacterial challenge, followed immediately by a 600‐mg/kg continuous infusion over 48 h) or administered an equivalent volume of phosphate‐buffered saline as previously described . Albumin was not used as the control solution in the second set of experiments to avoid binding heme, which is expected to increase after hemolysis . This study was stopped early due to the toxicity seen with Hp therapy.…”

Section: Methodsmentioning

confidence: 99%

Haptoglobin therapy has differential effects depending on severity of canine septic shock and cell‐free hemoglobin level

et al. 2019

View full text Add to dashboard Cite

BACKGROUND: During sepsis, higher plasma cell-free hemoglobin (CFH) levels portend worse outcomes. In sepsis models, plasma proteins that bind CFH improve survival. In our canine antibiotic-treated Staphylococcus aureus pneumonia model, with and without red blood cell (RBC) exchange transfusion, commercial human haptoglobin (Hp) concentrates bound and compartmentalized CFH intravascularly, increased CFH clearance, and lowered iron levels, improving shock, lung injury, and survival. We now investigate in our model how very high CFH levels and treatment time affect Hp's beneficial effects.ABBREVIATIONS: CFH = cell-free hemoglobin; Hp = haptoglobin; LIS = lung injury score; NTBI = non-transferrin-bound iron.From the

show abstract

“…Hemozoin, an insoluble crystalline of free heme, is essential to survive in hematophagous organisms, such as malaria parasites. In Vertebrates, free heme is specifically scavenged by extracellular heme-binding protein hemopexin, and alpha-1-microglobulin, or, by serum albumin [64]. Besides, HOs also protect cells from heme toxicity by catabolizing heme into iron, biliverdin, and CO.…”

Section: Heme-induced Toxicitymentioning

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

View full text Add to dashboard Cite

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.

show abstract

Heme-based catalytic properties of human serum albumin

Cited by 66 publications

References 92 publications

Novel Approach for Characterizing Propofol Binding Affinities to Serum Albumins from Different Species

Novel Approach for Characterizing Propofol Binding Affinities to Serum Albumins from Different Species

Haptoglobin therapy has differential effects depending on severity of canine septic shock and cell‐free hemoglobin level

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

Contact Info

Product

Resources

About