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Comparison of the oxidative reactivity of recombinant fetal and adult human hemoglobin: implications for the design of hemoglobin-based oxygen carriers.

Simons, Michelle and Gretton, Svetlana and Silkstone, Gary Ga and Rajagopal, Badri S and Allen-Baume, Victoria and Syrett, Natalie and Shaik, Thoufieq and Eriksson, Nelida and Ronda, Luca and Mozzarelli, Andrea and Strader, Michael B and Alayash, Abdu I and Reeder, Brandon J and Cooper, Chris E (2018) 'Comparison of the oxidative reactivity of recombinant fetal and adult human hemoglobin: implications for the design of hemoglobin-based oxygen carriers.' Bioscience Reports, 38 (4). ISSN 0144-8463

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Abstract

Hemoglobin based oxygen carriers (HBOCs) have been engineered to replace or augment the oxygen carrying capacity of erythrocytes. However, clinical results have generally been disappointing due, in part due to the intrinsic oxidative toxicity of hemoglobin. The most common HBOC starting material is adult human or bovine hemoglobin. However, it has been suggested that fetal hemoglobin may offer advantages due to decreased oxidative reactivity. Large scale manufacturing of a HBOC will likely ultimately require recombinant sources of human proteins. We therefore directly compared the functional properties and oxidative reactivity of recombinant fetal (rHbF) and recombinant adult (rHbA) hemoglobin. rHbA and rHbF produced similar yields of purified functional protein. No differences were seen in the two proteins in: autoxidation rate; the rate of hydrogen peroxide reaction; NO scavenging dioxygenase activity; and the NO producing nitrite reductase activity. The rHbF protein was: less damaged by low levels of hydrogen peroxide; less damaging when added to human umbilical vein endothelial cells (HUVEC) in the ferric form; and had a slower rate of intrinsic heme loss. The rHbA protein was: more readily reducible by plasma antioxidants such as ascorbate in both the reactive ferryl and ferric states; less readily damaged by lipid peroxides; and less damaging to phosphatidylcholine liposomes. In conclusion in terms of oxidative reactivity there are advantages and disadvantages to the use of recombinant adult or fetal Hb as the basis for an effective HBOC.

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science and Health > Biological Sciences, School of
Depositing User: Elements
Date Deposited: 09 Jul 2018 14:23
Last Modified: 09 Aug 2018 14:34
URI: http://repository.essex.ac.uk/id/eprint/22599

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