Current Challenges in the Development of Acellular Hemoglobin Oxygen Carriers by Protein Engineering.
Shock
; 52(1S Suppl 1): 28-40, 2019 10.
Article
en En
| MEDLINE
| ID: mdl-29112633
ABSTRACT
This article reviews the key biochemical mechanisms that govern O2 transport, NO scavenging, and oxidative degradation of acellular hemoglobin (Hb) and how these ideas have been used to try to develop strategies to engineer safer and more effective hemoglobin-based oxygen carriers (HBOCs). Significant toxicities due to acellular Hb have been observed after the administration of HBOCs or after the lysis of red cells, and include rapid clearance and kidney damage due to dissociation into dimers, haptoglobin binding, and macrophage activation; early O2 release leading to decreased tissue perfusion in capillary beds; interference with endothelial and smooth muscle signaling due to nitric oxide (NO) scavenging; autooxidization of heme iron followed by production of reactive oxygen species; and iron overload symptoms due to hemin loss, globin denaturation, iron accumulation, and further inflammation. Protein engineering can be used to mitigate some of these side effects, but requires an in-depth mechanistic understanding of the biochemical and biophysical features of Hb that regulate quaternary structure, O2 affinity, NO dioxygenation, and resistance to oxidation, hemin loss, and unfolding.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oxígeno
/
Hemoglobinas
/
Ingeniería de Proteínas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Shock
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
Año:
2019
Tipo del documento:
Article