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Comparison of the o...
Comparison of the oxidative reactivity of recombinant fetal and adult human hemoglobin : implications for the design of hemoglobin-based oxygen carriers
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- Simons, Michelle (författare)
- University of Essex
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- Gretton, Svetlana (författare)
- University of Essex
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- Silkstone, Gary G.A. (författare)
- University of Essex
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- Rajagopal, Badri S. (författare)
- University of Essex
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- Allen-Baume, Victoria (författare)
- University of Essex
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- Syrett, Natalie (författare)
- University of Essex
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- Shaik, Thoufieq (författare)
- University of Essex
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- Leiva-Eriksson, Nelida (författare)
- Lund University,Lunds universitet,Tillämpad biokemi,Centrum för tillämpade biovetenskaper,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Pure and Applied Biochemistry,Center for Applied Life Sciences,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
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- Ronda, Luca (författare)
- University of Parma
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- Mozzarelli, Andrea (författare)
- University of Parma,CNR Institute of Biophysics (IBF)
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- Strader, Michael B. (författare)
- United States Food and Drug Administration
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- Alayash, Abdu I. (författare)
- United States Food and Drug Administration
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- Reeder, Brandon J. (författare)
- University of Essex
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- Cooper, Chris E. (författare)
- University of Essex
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(creator_code:org_t)
- 2018
- 2018
- Engelska.
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Ingår i: Bioscience Reports. - 0144-8463. ; 38:4
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Hemoglobin (Hb)-based oxygen carriers (HBOCs) have been engineered to replace or augment the oxygen carrying capacity of erythrocytes. However, clinical results have generally been disappointing, in part due to the intrinsic oxidative toxicity of Hb. The most common HBOC starting material is adult human or bovine Hb. However, it has been suggested that fetal Hb may offer advantages due to decreased oxidative reactivity. Large-scale manufacturing of HBOC will likely and 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) Hb. 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 rHbA or rHbF as the basis for an effective HBOC.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
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Simons, Michelle
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Gretton, Svetlan ...
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Silkstone, Gary ...
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Rajagopal, Badri ...
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Allen-Baume, Vic ...
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Syrett, Natalie
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visa fler...
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Shaik, Thoufieq
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Leiva-Eriksson, ...
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Ronda, Luca
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Mozzarelli, Andr ...
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Strader, Michael ...
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Alayash, Abdu I.
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Reeder, Brandon ...
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Cooper, Chris E.
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