TY - JOUR
T1 - NO and CO binding profiles of hemoglobin vesicles as artificial oxygen carriers
AU - Sakai, Hiromi
AU - Sato, Atsushi
AU - Sobolewski, Peter
AU - Takeoka, Shinji
AU - Frangos, John A.
AU - Kobayashi, Koichi
AU - Intaglietta, Marcos
AU - Tsuchida, Eishun
N1 - Funding Information:
The authors would like to thank Dr. Hirohisa Horinouchi (Keio University), Dr. Amy G. Tsai and Dr. Pedro Cabrales (University of California, San Diego), and Dr. Keitaro Sou (Waseda University) for valuable discussions. This work was supported in part by the grant for the Health Sciences Research including Drug Innovation from the Ministry of Health, Labour and Welfare, Japan, Grants in Aid for Scientific Research (B) from the Japan Society for the Promotion of Science (19300164), and USPHS Bioengineering Research Partnership grant R24-HL 64395, R01-HL62354 and P01-HL71064.
PY - 2008/10
Y1 - 2008/10
N2 - Hemoglobin vesicles (HbVs) are artificial oxygen carriers encapsulating purified and concentrated Hb solution in phospholipid vesicles (liposomes). We examined in-vitro reaction profiles of a formulation of HbV with NO and CO in anaerobic and aerobic conditions using stopped-flow spectrophotometry and a NO electrode. Reaction rate constants of NO to deoxygenated and oxygenated HbV were considerably smaller than those of cell-free Hb because of the intracellular NO-diffusion barrier. The reaction of CO with deoxygenated HbV was slightly slower than that of cell-free Hb solely because of the co-encapsulated allosteric effector, pyridoxal 5'-phosphate. The NO depletion in an aerobic condition in the presence of empty vesicles was monitored using a NO electrode, showing that the hydrophobic bilayer membrane of HbV, which might have higher gas solubility, does not markedly facilitate the O2 and NO reaction, and that the intracellular Hb is the major component of NO depletion. In conclusion, HbV shows retarded gas reactions, providing some useful information to explain the absence of vasoconstriction and hypertension when they are intravenously injected.
AB - Hemoglobin vesicles (HbVs) are artificial oxygen carriers encapsulating purified and concentrated Hb solution in phospholipid vesicles (liposomes). We examined in-vitro reaction profiles of a formulation of HbV with NO and CO in anaerobic and aerobic conditions using stopped-flow spectrophotometry and a NO electrode. Reaction rate constants of NO to deoxygenated and oxygenated HbV were considerably smaller than those of cell-free Hb because of the intracellular NO-diffusion barrier. The reaction of CO with deoxygenated HbV was slightly slower than that of cell-free Hb solely because of the co-encapsulated allosteric effector, pyridoxal 5'-phosphate. The NO depletion in an aerobic condition in the presence of empty vesicles was monitored using a NO electrode, showing that the hydrophobic bilayer membrane of HbV, which might have higher gas solubility, does not markedly facilitate the O2 and NO reaction, and that the intracellular Hb is the major component of NO depletion. In conclusion, HbV shows retarded gas reactions, providing some useful information to explain the absence of vasoconstriction and hypertension when they are intravenously injected.
KW - Artificial red cells
KW - Blood substitutes
KW - CO
KW - Liposome
KW - NO
KW - Vasoconstriction
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U2 - 10.1016/j.bbapap.2008.03.007
DO - 10.1016/j.bbapap.2008.03.007
M3 - Article
C2 - 18405675
AN - SCOPUS:52049120129
SN - 1570-9639
VL - 1784
SP - 1441
EP - 1447
JO - BBA - Protein Structure
JF - BBA - Protein Structure
IS - 10
ER -