scholarly journals Subunit assembly of hemoglobin: an important determinant of hematologic phenotype

Blood ◽  
1987 ◽  
Vol 69 (1) ◽  
pp. 1-6 ◽  
Author(s):  
HF Bunn
Keyword(s):  
Electrostatic Interactions ◽  
Hemoglobin Concentration ◽  
Cytoskeletal Proteins ◽  
Membrane Receptors ◽  
Target Cells ◽  
Red Cell Membrane ◽  
Alpha Beta ◽  
The Difference ◽  
Polypeptide Chains ◽  
Positively Charged

Hemoglobin's physiologic properties depend on the orderly assembly of its subunits in erythropoietic cells. The biosynthesis of alpha- and beta-globin polypeptide chains is normally balanced. Heme rapidly binds to the globin subunit, either during translation or shortly thereafter. The formation of the alpha beta-dimer is facilitated by electrostatic attraction of a positively charged alpha-subunit to a negatively charged beta-subunit. The alpha beta-dimer dissociates extremely slowly. The difference between the rate of dissociation of alpha beta- and alpha gamma-dimers with increasing pH explains the well-known alkaline resistance of Hb F. Two dimers combine to form the functioning alpha 2 beta 2-tetramer. This model of hemoglobin assembly explains the different levels of positively charged and negatively charged mutant hemoglobins that are encountered in heterozygotes and the effect of alpha-thalassemia and heme deficiency states in modifying the level of the variant hemoglobin as well as Hb A2. Electrostatic interactions also affect the binding of hemoglobin to the cytoplasmic surface of the red cell membrane and may underlie the formation of target cells. Enhanced binding of positively charged variants such as S and C trigger a normally dormant pathway for potassium and water loss. Thus, the positive charge on beta c is responsible for the two major contributors to the pathogenesis of Hb SC disease: increased proportion of Hb S and increased intracellular hemoglobin concentration. It is likely that electrostatic interactions play an important role in the assembly of a number of other multisubunit macromolecules, including membrane receptors, cytoskeletal proteins, and DNA binding proteins.

scholarly journals Subunit assembly of hemoglobin: an important determinant of hematologic phenotype

Blood ◽  
1987 ◽  
Vol 69 (1) ◽  
pp. 1-6 ◽  
Author(s):  
HF Bunn
Keyword(s):  
Electrostatic Interactions ◽  
Hemoglobin Concentration ◽  
Cytoskeletal Proteins ◽  
Membrane Receptors ◽  
Target Cells ◽  
Red Cell Membrane ◽  
Alpha Beta ◽  
The Difference ◽  
Polypeptide Chains ◽  
Positively Charged

Abstract Hemoglobin's physiologic properties depend on the orderly assembly of its subunits in erythropoietic cells. The biosynthesis of alpha- and beta-globin polypeptide chains is normally balanced. Heme rapidly binds to the globin subunit, either during translation or shortly thereafter. The formation of the alpha beta-dimer is facilitated by electrostatic attraction of a positively charged alpha-subunit to a negatively charged beta-subunit. The alpha beta-dimer dissociates extremely slowly. The difference between the rate of dissociation of alpha beta- and alpha gamma-dimers with increasing pH explains the well-known alkaline resistance of Hb F. Two dimers combine to form the functioning alpha 2 beta 2-tetramer. This model of hemoglobin assembly explains the different levels of positively charged and negatively charged mutant hemoglobins that are encountered in heterozygotes and the effect of alpha-thalassemia and heme deficiency states in modifying the level of the variant hemoglobin as well as Hb A2. Electrostatic interactions also affect the binding of hemoglobin to the cytoplasmic surface of the red cell membrane and may underlie the formation of target cells. Enhanced binding of positively charged variants such as S and C trigger a normally dormant pathway for potassium and water loss. Thus, the positive charge on beta c is responsible for the two major contributors to the pathogenesis of Hb SC disease: increased proportion of Hb S and increased intracellular hemoglobin concentration. It is likely that electrostatic interactions play an important role in the assembly of a number of other multisubunit macromolecules, including membrane receptors, cytoskeletal proteins, and DNA binding proteins.

Characteristics of the Interaction between Thrombin Exosite1 and the Sequence 269-297 of Platelet Glycoprotein Ibα

1998 ◽  
Vol 80 (08) ◽  
pp. 310-315 ◽  
Author(s):  
Marie-Christine Bouton ◽  
Christophe Thurieau ◽  
Marie-Claude Guillin ◽  
Martine Jandrot-Perrus
Keyword(s):  
Platelet Activation ◽  
Electrostatic Interactions ◽  
Platelet Glycoprotein ◽  
Thrombin Receptor ◽  
Central Position ◽  
Amidolytic Activity ◽  
N Terminus ◽  
Hydrolysis Of ◽  
Chemical Cross Linking ◽  
Positively Charged

SummaryThe interaction between GPIb and thrombin promotes platelet activation elicited via the hydrolysis of the thrombin receptor and involves structures located on the segment 238-290 within the N-terminal domain of GPIbα and the positively charged exosite 1 on thrombin. We have investigated the ability of peptides derived from the 269-287 sequence of GPIbα to interact with thrombin. Three peptides were synthesized, including Ibα 269-287 and two scrambled peptides R1 and R2 which are comparable to Ibα 269-287 with regards to their content and distribution of anionic residues. However, R2 differs from both Ibα 269-287 and R1 by the shifting of one proline from a central position to the N-terminus. By chemical cross-linking, we observed the formation of a complex between 125I-Ibα 269-287 and α-thrombin that was inhibited by hirudin, the C-terminal peptide of hirudin, sodium pyrophosphate but not by heparin. The complex did not form when γ-thrombin was substituted for α-thrombin. Ibα 269-287 produced only slight changes in thrombin amidolytic activity and inhibited thrombin binding to fibrin. R1 and R2 also formed complexes with α-thrombin, modified slightly its catalytic activity and inhibited its binding to fibrin. Peptides Ibα 269-287 and R1 inhibited platelet aggregation and secretion induced by low thrombin concentrations whereas R2 was without effect. Our results indicate that Ibα 269-287 interacts with thrombin exosite 1 via mainly electrostatic interactions, which explains why the scrambled peptides also interact with exosite 1. Nevertheless, the lack of effect of R2 on thrombin-induced platelet activation suggests that proline 280 is important for thrombin interaction with GPIb.

scholarly journals Hemoglobin Oxidation in Stored Blood Accelerates Hemolysis and Oxidative Injury to Red Blood Cells

2020 ◽  
Vol 12 (04) ◽  
pp. 244-249
Author(s):  
Ibrahim Mustafa ◽  
Tameem Ali Qaid Hadwan
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Morphological Changes ◽  
Hemoglobin Concentration ◽  
Red Cell Membrane ◽  
Rbc Membrane ◽  
Hemoglobin Oxidation ◽  
Rbc Indices ◽  
Methemoglobin Formation ◽  
Stored Blood

Abstract Introduction Maintaining blood supply is a challenge in blood banks. Red blood cells (RBCs) stored at 4°C experience issues of biochemical changes due to metabolism of cells, leading to changes collectively referred to as “storage lesions.” Oxidation of the red cell membrane, leading to lysis, contributes to these storage lesions. Methods Blood bags with CPD-SAGM stored at 4°C for 28 days were withdrawn aseptically on days 1, 14, and 28. Hematology analyzer was used to investigate RBC indices. Hemoglobin oxidation was studied through spectrophotometric scan of spectral change. RBC lysis was studied with the help of Drabkin's assay, and morphological changes were observed by light and scan electron microscopy. Results RBCs show progressive changes in morphology echinocytes and spherocytes on day 28. There was 0.85% RBC lysis, an approximately 20% decrease in percentage oxyhemoglobin, and a 14% increase in methemoglobin formation, which shows hemoglobin oxidation on day 28. Conclusions Oxidative damage to RBC, with an increase in storage time was observed in the present study. The observed morphological changes to RBC during the course of increased time shows that there is progressive damage to RBC membrane and a decrease in hemoglobin concentration; percentage RBC lysis is probably due to free hemoglobin and iron.

scholarly journals THU0236 EFFICACY AND SAFETY OF NON-MITOGENIC ANTICD3 ANTIBODY ADMINISTRATION IN THE TREATMENT OF LUPUS-PRONE MICE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 345.1-345
Author(s):  
M. Morita ◽  
S. Masuyama ◽  
M. Mizui ◽  
Y. Isaka
Keyword(s):  
T Cells ◽  
Antibody Titer ◽  
Cell Function ◽  
Cell Subpopulation ◽  
Target Cells ◽  
Therapeutic Effects ◽  
Autoantibody Production ◽  
Rate Of Increase ◽  
Dsdna Antibody ◽  
The Difference

Background:Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by the production of autoantibody and systemic tissue damages including glomerulonephritis. Immune responses mediated by autoreactive T-cells, as well as by autoantibody, is involved in the development and progression of end-organ damages1. Biologic agents which manipulate T-cell function such as CTLA4-Ig and anti-CD40L have been revisited and tried to treat human SLE, however, both of them failed to demonstrate efficacy.A mouse specific anti-CD3ε mAb, clone 145-2C11 (2C11) is known to be immunosuppressive by down-modulation of TCR and depletion of T-cells2. Administration of Fc-deleted 145-2C11 F(ab’)2to lupus-prone mice was reported to reduce lymphadenopathy and prolong survival, but had no significant effect on anti-DNA antibody titer3. The mechanisms by which 2C11 ameliorates lupus are still unclear.In this study, we used non-mitogenic Fc-modified silent 145-2c11 (2C11S), which disables interaction between target cells and Fc receptor-bearing cells, abolishes antibody directed cytotoxicity, and has longer half-life than F(ab’)2. 2C11S is expected to exert its effect in safe and stable as compared with functional parent-2C11 (2C11P) antibody.Objectives:The purpose of our study is to clarify the difference between 2C11S and 2C11P and to examine their therapeutic effects against murine lupus-prone (NZB/W F1) mice.Methods:20 μg of 2C11P (absolute antibody), 2C11S (absolute antibody), or isotype control immunoglobulin G1 κ (IC)(BioLegend) were administered intraperitoneally to C57BL6 mice. The difference of their action on T-cells were evaluated in a time series from peripheral blood. Plasma cytokine levels were measured within 24 hours after antibody administration.In NZB/W F1 mice from weeks 10 or 20, 2C11P, 2C11S, and IC were administered (100 μg / week, 4 times, intraperitoneally). Plasma anti-dsDNA antibody titer, spleen and kidney blood cell subpopulation, and histology of renal tissue were evaluated before and/or after treatment.Results:Duration of reduced TCR expression in 2C11S group was approximately twice as long as that in 2C11P group, and the levels of plasma TNF-α was not increased in 2C11S group while significant increase was observed in 2C11P group (IC; mean 48.3 ± SD 16.7 pg/ml, 2C11S; 57.9 ± 6.12, 2C11P; 168 ± 50.6, IC VS 2C11S; p>0.99, IC VS 2C11P; p=0.03, ANOVA).In NZB/W F1 mice, the number of follicular helper T (Tfh) cells in spleen significantly decreased in 2C11S group (IC; median 9.0*104[interquartile range 8.5*104], 2C11S; 1.8*104[1.0*104], 2C11P; 1.0*105[9.4*104], IC VS 2C11S; p=0.03, IC VS 2C11P; p>0.99, Kruskal-Wallis). The number of germinal center B (GCB) cells in spleen also decreased in 2C11S group (IC; 1.2*105[1.7*105], 2C11S; 9.0*103[2.3*104], 2C11P; 8.0*104[2.3*105], IC VS 2C11S; p=0.03, IC VS 2C11P; p>0.99). The number of infiltrating CD4+T-cells in kidney significantly reduced in 2C11S group (IC; 3.4*103[1.0*104], 2C11S; 6.4*102[8.8*102], 2C11P; 1.2*103[4.4*103], IC VS 2C11S; p=0.048, IC VS 2C11P; p=0.23). In addition, the rate of increase in anti-dsDNA IgG titers significantly decreased in 2C11S group (IC; 2.3 [1.3], 2C11S; 0.9 [1.0], 2C11P; 1.3 [1.4], IC VS 2C11S; p=0.03, IC VS 2C11P; p=0.24). Finally, glomerular hypercellularity was markedly alleviated only in 2C11S group (IC; 4.4*10 [8.4], 2C11S; 3.8*10 [1.1], 2C11P; 3.9*10 [8.2], IC VS 2C11S; p=0.02, IC VS 2C11P; p=0.57).Conclusion:2C11S did not induce cytokine release with maintaining longer effect on TCR down-modulation. 2C11S reduced autoantibody production by suppressing GCB differentiation, possibly through down-regulation of Tfh cell number. Consequently, 2C11S ameliorated lupus nephritis. On the other hand, 2C11P did not show therapeutic effect.References:[1]George C Tsokos. et al. Nat. Rev. Rheum (2016) 12: 716-730.[2]Kuhn C. et al. Immunotherapy (2016) 8: 889-906.[3]Henrickson M. et al. Arthritis Rheum (1994) 37: 587-589.Disclosure of Interests: :None declared

scholarly journals The C-terminal peptide of CCL21 drastically augments CCL21 activity through the dendritic cell lymph node homing receptor CCR7 by interaction with the receptor N-terminus

2021 ◽  
Author(s):  
Astrid Sissel Jørgensen ◽  
Emma Probst Brandum ◽  
Jeppe Malthe Mikkelsen ◽  
Klaudia A. Orfin ◽  
Ditte Rahbæk Boilesen ◽  
...  
Keyword(s):  
Lymph Node ◽  
Electrostatic Interactions ◽  
Immune Cell ◽  
Direct Interaction ◽  
Receptor Interaction ◽  
Binding Model ◽  
Lymph Node Homing ◽  
Gating Mechanism ◽  
N Terminus ◽  
Positively Charged

AbstractThe endogenous chemokines CCL19 and CCL21 signal via their common receptor CCR7. CCL21 is the main lymph node homing chemokine, but a weak chemo-attractant compared to CCL19. Here we show that the 41-amino acid positively charged peptide, released through C-terminal cleavage of CCL21, C21TP, boosts the immune cell recruiting activity of CCL21 by up to 25-fold and the signaling activity via CCR7 by ~ 100-fold. Such boosting is unprecedented. Despite the presence of multiple basic glycosaminoglycan (GAG) binding motifs, C21TP boosting of CCL21 signaling does not involve interference with GAG mediated cell-surface retention. Instead, boosting is directly dependent on O-glycosylations in the CCR7 N-terminus. As dictated by the two-step binding model, the initial chemokine binding involves interaction of the chemokine fold with the receptor N-terminus, followed by insertion of the chemokine N-terminus deep into the receptor binding pocket. Our data suggest that apart from a role in initial chemokine binding, the receptor N-terminus also partakes in a gating mechanism, which could give rise to a reduced ligand activity, presumably through affecting the ligand positioning. Based on experiments that support a direct interaction of C21TP with the glycosylated CCR7 N-terminus, we propose that electrostatic interactions between the positively charged peptide and sialylated O-glycans in CCR7 N-terminus may create a more accessible version of the receptor and thus guide chemokine docking to generate a more favorable chemokine-receptor interaction, giving rise to the peptide boosting effect.

scholarly journals Influence of Network Multimedia Nutritional Supplements on Basketball Exercise Fatigue Based on Embedded Microprocessor

2022 ◽  
Vol 2022 ◽  
pp. 1-13
Author(s):  
Qiao Chen ◽  
Shihong Liu
Keyword(s):  
Hemoglobin Concentration ◽  
Nutritional Supplements ◽  
Weight Lifting ◽  
The Body ◽  
Control Group ◽  
Energy Materials ◽  
Long Distance ◽  
Basketball Players ◽  
The Difference ◽  
Experimental Group

Sports can cause the consumption of energy materials in the body. The rational use of nutritional supplements can maintain the homeostasis of the organism, which plays a very important role in improving the competitive performance of sports athletes. The purpose of this study is to explore the effect of nutritional supplements on basketball sports fatigue. The method of this study is as follows: first of all, 15 basketball players in our city were selected as the experimental objects, and they were randomly divided into the experimental group and the control group. The members of the experimental group took nutrients. After the training, 6 days a week, 3 hours in the morning and 3 hours in the afternoon, and the rest was adjusted on Sunday. Before training, four weeks and eight weeks of training, the blood routine indexes and body functions of athletes were tested. The results showed that the number of red blood cells, hemoglobin concentration, and average hemoglobin concentration of ligustilide supplement of the athletes were at the level of 0.05 after 4 weeks and 8 weeks, and the difference was significant ( P < 0.05 ). The nutritional supplements were used in sprint (3.4 s less), long-distance running (12.8 s less), and weight lifting (6.2 kg more) to a certain extent. Nutritional supplements are used as an auxiliary means of diet to supplement the amino acids, trace elements, vitamins, minerals, etc. required by the human body. The conclusion is that nutrition supplement can effectively improve the indexes of athletes’ body in about four weeks, but the effect is not obvious after a long time. This study provides a certain method for the research of nutritional supplements in the field of sports.

scholarly journals Upper Critical Solution Temperature (UCST) Behavior of Coacervate of Cationic Protamine and Multivalent Anions

Polymers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 691 ◽  
Author(s):  
Hyungbin Kim ◽  
Byoung-jin Jeon ◽  
Sangsik Kim ◽  
YongSeok Jho ◽  
Dong Soo Hwang
Keyword(s):  
Electrostatic Interactions ◽  
Solution Temperature ◽  
Complex Coacervation ◽  
Critical Factors ◽  
Critical Solution Temperature ◽  
Temperature Changes ◽  
Upper Critical Solution Temperature ◽  
Large Asymmetry ◽  
Positively Charged ◽  
Liquid Liquid Phase Separation

Complex coacervation is an emerging liquid/liquid phase separation (LLPS) phenomenon that behaves as a membrane-less organelle in living cells. Yet while one of the critical factors for complex coacervation is temperature, little analysis and research has been devoted to the temperature effect on complex coacervation. Here, we performed a complex coacervation of cationic protamine and multivalent anions (citrate and tripolyphosphate (TPP)). Both mixtures (i.e., protamine/citrate and protamine/TPP) underwent coacervation in an aqueous solution, while a mixture of protamine and sodium chloride did not. Interestingly, the complex coacervation of protamine and multivalent anions showed upper critical solution temperature (UCST) behavior, and the coacervation of protamine and multivalent anions was reversible with solution temperature changes. The large asymmetry in molecular weight between positively charged protamine (~4 kDa) and the multivalent anions (<0.4 kDa) and strong electrostatic interactions between positively charged guanidine residues in protamine and multivalent anions were likely to contribute to UCST behavior in this coacervation system.

scholarly journals COVID 19: An Epidemiological and Host Genetics Appraisal

2020 ◽  
Vol 11 (3) ◽  
pp. 71-76 ◽  
Author(s):  
Arup Ratan Bandyopadhyay ◽  
Diptendu Chatterjee ◽  
Kusum Ghosh ◽  
Pranabesh Sarkar
Keyword(s):  
Indian Population ◽  
Severe Pneumonia ◽  
Target Cells ◽  
Health Issues ◽  
Prognosis Factors ◽  
Tissue Concentrations ◽  
The World ◽  
Recent Outbreak ◽  
The Difference ◽  
Viral Receptors

Coronaviruses (CoVs) is a single single-strand RNA genome approximately 26 - 32 kb in size. Out of the seven coronaviruses, three HCoVs (Human CoVs) have been discovered that causes severe pneumonia such as Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) and recently recognized SARS-CoV-2, which possesses varying degrees of lethality worldwide and happened to be bioterrorism in terms of the recent outbreak through human-to-human transmission from China to all over the world. Epidemiological and Clinical study on SARS-COV-2 have recently been reported world-wide but lack of data on prognosis factors including effective medicine or vaccine are yet to be clinically approved to prevent this infectious disease. Human pathogenic coronaviruses SARS-CoV-2 bind to their target cells through ACE2, which is expressed by epithelial cells of the lung, intestine, kidney, and blood vessels. The difference in distribution, maturation, and functioning of viral receptors could be considered as a possible reason for the genetic heterogeneity of ACE2, and age and sex related difference in the incidence of the disease such as, the positive correlation with ACE2 expression and age including the severity of the infection of SARS-CoV-2. Since the ACE2 location in X chromosome, therefore, the males presumable might have more morbidity and mortality by SARS-CoV-2 than females due to sex-based immunological differences like greater observable circulating level of ACE2 in males or else it may be due to the patterns of life style variables such as prevalence of smoking among the males. Additionally, the Angiotensin-Converting Enzyme 1 (ACE1) is characterized by a genetic insertion/deletion (I/D) polymorphism in intron 16, which is associated with alterations in circulating and tissue concentrations of ACE, where the study reported as D allele is associated with a reduced expression of ACE2. Nevertheless, studies from different states of Indian population on ACE I/D gene polymorphism shows higher frequency of I allele which might explain the lower prevalence of SARS-CoV-2 in Indian population and consequently be subject matter of research of SARS-CoV-2 on epidemiological and public health issues.

Limitations in predicting oxyhemoglobin saturation of dog blood from PO2

1980 ◽  
Vol 239 (5) ◽  
pp. H703-H705
Author(s):  
D. Saito ◽  
R. A. Olsson
Keyword(s):  
Error Estimates ◽  
Hemoglobin Concentration ◽  
Absolute Difference ◽  
Oxyhemoglobin Saturation ◽  
Blood Samples ◽  
Dog Blood ◽  
The Difference

This study compared oxyhemoglobin saturation (SO2) and O2 content (CO2) estimated from O2 tension (PO2) by the Rossing-Cain nomogram (J. Appl. Physiol. 21: 195-201, 1966) with SO2 and CO2 estimated by a galvanometric O2 analyzer in blood samples from eight dogs. The nomogram consistently and significantly overestimated SO2 over the range of 20-60%. The greatest absolute difference, which averaged 10% saturation, was between 40 and 59% saturation. Between 30 and 39% saturation, the difference averaged 30% of SO2 estimated galvanometrically. CO2, calculated as the product of SO2, hemoglobin concentration (cyanmethemoglobin method), and hemoglobin O2 capacity, was significantly overestimated by the nomogram by as much as 1.2 ml/dl between 2 and 9.9 ml/dl. Between 14 and 21.9 ml/dl, the nomogram underestimated CO2 by as much as 1.2 ml/dl. We conclude that because coronary venous SO2 and CO2 values normally lie in the range of greatest error, estimates of these values based on PO2 are particularly unsuited for studies of myocardial O2 usage.

scholarly journals Antisickling effect of tellurite: a potent membrane-acting agent in vitro

Blood ◽  
1984 ◽  
Vol 64 (1) ◽  
pp. 305-307 ◽  
Author(s):  
T Asakura ◽  
Y Shibutani ◽  
MP Reilly ◽  
RH DeMeio
Keyword(s):  
Hemoglobin Concentration ◽  
Inhibitory Effect ◽  
Red Cells ◽  
Cell Swelling ◽  
Red Cell ◽  
Red Cell Membrane ◽  
Potassium Tellurite ◽  
New Type ◽  
Acting Agent

Abstract Potassium tellurite (K2TeO3) was found to be a potent antisickling agent that inhibited red cell sickling at concentrations less than 10 mumol/L. The inhibitory effect depended on the incubation time, with the effect increasing with longer incubation periods. Because tellurite causes swelling of red cells, and because the antisickling effect of tellurite correlated with the degree of red cell swelling, the antisickling effect of tellurite is assumed to be due to the decreased mean cell hemoglobin concentration. Swelling of red cells by tellurite was accelerated by the addition of reduced glutathione. Tellurite appears to be a new type of antisickling agent that interacts with the red cell membrane.

Sign in / Sign up

Export Citation Format

Share Document