The βLys66Tyr Variant of Human Hemoglobin as a Component of a Blood Substitute

Author(s):  
R. S. Silkstone ◽  
G. Silkstone ◽  
J. A. Baath ◽  
B. Rajagopal ◽  
P. Nicholls ◽  
...  
2006 ◽  
Vol 282 (7) ◽  
pp. 4894-4907 ◽  
Author(s):  
Yiping Jia ◽  
Paul W. Buehler ◽  
Robert A. Boykins ◽  
Richard M. Venable ◽  
Abdu I. Alayash

Hydrogen peroxide (H2O2) triggers a redox cycle between ferric and ferryl hemoglobin (Hb) leading to the formation of a transient protein radical and a covalent hemeprotein cross-link. Addition of H2O2 to highly purified human hemoglobin (HbA0) induced structural changes that primarily resided within β subunits followed by the internalization of the heme moiety within α subunits. These modifications were observed when an equal molar concentration of H2O2 was added to HbA0 yet became more abundant with greater concentrations of H2O2. Mass spectrometric and amino acid analysis revealed for the first time that βCys-93 and βCys-112 were oxidized extensively and irreversibly to cysteic acid when HbA0 was treated with H2O2. Oxidation of further amino acids in HbA0 exclusive to the β-globin chain included modification of βTrp-15 to oxyindolyl and kynureninyl products as well as βMet-55 to methionine sulfoxide. These findings may therefore explain the premature collapse of the β subunits as a result of the H2O2 attack. Analysis of a tryptic digest of the main reversed phase-high pressure liquid chromatography fraction revealed two α-peptide fragments (α128 - α139) and a heme moiety with the loss of iron, cross-linked between αSer-138 and the porphyrin ring. The novel oxidative pathway of HbA0 modification detailed here may explain the diverse oxidative, toxic, and potentially immunogenic effects associated with the release of hemoglobin from red blood cells during hemolytic diseases and/or when cell-free Hb is used as a blood substitute.


1988 ◽  
Vol 17 (2) ◽  
pp. 143-154 ◽  
Author(s):  
S.M. Christensen ◽  
F. Medina ◽  
R.W. Winslow ◽  
S.M. Snell ◽  
A. Zegna ◽  
...  

1991 ◽  
Vol 101 (5) ◽  
pp. 1345-1353 ◽  
Author(s):  
H.Fletcher Starkes ◽  
Anand Tewari ◽  
Kimon Flokas ◽  
Jon C. Kosek ◽  
Daniel Brown ◽  
...  

Author(s):  
J.S. Geoffroy ◽  
R.P. Becker

The pattern of BSA-Au uptake in vivo by endothelial cells of the venous sinuses (sinusoidal cells) of rat bone marrow has been described previously. BSA-Au conjugates are taken up exclusively in coated pits and vesicles, enter and pass through an “endosomal” compartment comprised of smooth-membraned tubules and vacuoles and cup-like bodies, and subsequently reside in multivesicular and dense bodies. The process is very rapid, with BSA-Au reaching secondary lysosmes one minute after presentation. (Figure 1)In further investigations of this process an isolated limb perfusion method using an artificial blood substitute, Oxypherol-ET (O-ET; Alpha Therapeutics, Los Angeles, CA) was developed. Under nembutal anesthesia, male Sprague-Dawley rats were laparotomized. The left common iliac artery and vein were ligated and the right iliac artery was cannulated via the aorta with a small vein catheter. Pump tubing, preprimed with oxygenated 0-ET at 37°C, was connected to the cannula.


2018 ◽  
Vol 2 (1) ◽  
pp. 20-25
Author(s):  
Hamid KARIMOV ◽  
◽  
Shavkat ALIYEV ◽  
Larisa SHEVCHENKO ◽  
Timur ALIMOV
Keyword(s):  

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