Recombinant Octameric Hemoglobins as Resuscitation Fluids in a Murine Model of Traumatic Brain Injury Plus Hemorrhagic Shock

Wu, Xianren; Ho, Nancy T.; Shen, Tong-Jian; Vagni, Vincent; Shellington, David; Janesko‐Feldman, Keri; Tam, Tsuey Chyi S.; Tam, Ming F.; Kochanek, Patrick M.; Ho, Chien; Simplăceanu, Virgil

doi:10.1007/978-3-642-40717-8_13

Cited by 2 publications

(5 citation statements)

References 56 publications

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“…However, the ␣L29F mutant has high, whereas the ␣L29W mutant has low O 2 binding affinity (15). We have found that the high O 2 affinity ␣L29F mutant has the lowest numerical brain tissue oxygen concentration and unexpectedly a better neuronal survival (34). Interestingly, Eaton et al (63) have reported that Hb with higher O 2 affinity gave better protection to animals placed at greatly reduced environmental oxygen pressures.…”

Section: Discussionmentioning

confidence: 75%

“…Combination of these mutations produced octameric macromolecules with unique properties that were utilized as resuscitation solutions in mice suffering traumatic brain injury combined with hemorrhagic shock. We observed that the high oxygen affinity rHb (␣N78C/L29F) conferred a neuroprotective effect in the selectively vulnerable region of the hippocampus (34).…”

Section: Hemoglobin (Hb)mentioning

confidence: 82%

“…We have recently employed recombinant octameric hemoglobins carrying ␣B10Leu to phenylalanine or tryptophan replacements as resuscitation solutions in mice after experimental traumatic brain injury plus hemorrhagic shock (34). Both mutants have reduced rates of NO-induced oxidation.…”

Section: Discussionmentioning

confidence: 99%

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Autoxidation and Oxygen Binding Properties of Recombinant Hemoglobins with Substitutions at the αVal-62 or βVal-67 Position of the Distal Heme Pocket

Tam

Rice

Maillett

et al. 2013

Journal of Biological Chemistry

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Background: Tertiary structure of the ligand binding pocket influences oxygen binding and autoxidation of hemoglobin. Results: E11 mutants have increased autoxidation rate. ␤E11Phe increases, whereas ␤E11Ile decreases the oxygen binding affinity of hemoglobin. Conclusion: Bulky residues at ␤E11 affect ligand binding and cause noticeable tertiary structural changes at the heme pockets. Significance: Hemoglobin distal heme pocket mutations alter oxygen binding properties without changing the quaternary structure.

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Section: Discussionmentioning

confidence: 75%

Section: Hemoglobin (Hb)mentioning

confidence: 82%

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Autoxidation and Oxygen Binding Properties of Recombinant Hemoglobins with Substitutions at the αVal-62 or βVal-67 Position of the Distal Heme Pocket

Tam

Rice

Maillett

et al. 2013

Journal of Biological Chemistry

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“…The mutation aN78C has been also associated with the aL29F or with aL29W mutation leading to an increase or decrease in oxygen affinity, respectively [38]. The group of Ho has shown that the administration of an octameric Hb (rHb aN78C, rHb aN78C/L29F or rHb aN78C/L29W) as resuscitation solution in mice after traumatic brain injury combined with hemorrhagic shock allows restoration of systemic hemodynamics (normalization of mean arterial blood pressure) and normalization of markers of global tissue metabolism, which are much better than lactated Ranger's solution [38]. The rHb aN78C/L29F with high oxygen affinity confers acute neuroprotection assessed at 24 h after injury [38].…”

Section: Discussionmentioning

confidence: 99%

“…The group of Ho has shown that the administration of an octameric Hb (rHb aN78C, rHb aN78C/L29F or rHb aN78C/L29W) as resuscitation solution in mice after traumatic brain injury combined with hemorrhagic shock allows restoration of systemic hemodynamics (normalization of mean arterial blood pressure) and normalization of markers of global tissue metabolism, which are much better than lactated Ranger's solution [38]. The rHb aN78C/L29F with high oxygen affinity confers acute neuroprotection assessed at 24 h after injury [38].…”

Section: Discussionmentioning

confidence: 99%

Interaction of recombinant octameric hemoglobin with endothelial cells

Gaucher¹,

Domingues-Hamdi²,

Prin-Mathieu³

et al. 2014

Comptes Rendus. Biologies

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Hemoglobin-based oxygen carriers (HBOCs) may generate oxidative stress, vasoconstriction and inflammation. To reduce these undesirable vasoactive properties, we increased hemoglobin (Hb) molecular size by genetic engineering with octameric Hb, recombinant (r) HbbG83C. We investigate the potential side effects of rHbbG83C on endothelial cells. The rHbbG83C has no impact on cell viability, and induces a huge repression of endothelial nitric oxide synthase gene transcription, a marker of vasomotion. No induction of Intermolecular-Adhesion Molecule 1 and E-selectin (inflammatory markers) transcription was seen. In the presence of rHbbG83C, the transcription of heme oxygenase-1 (oxidative stress marker) is weakly increased compared to the two other HBOCs (references) or Voluven (control). This genetically engineered octameric Hb, based on a human Hb bG83C mutant, leads to little impact at the level of endothelial cell inflammatory response and thus appears as an interesting molecule for HBOC development.ß 2014 Published by Elsevier Masson SAS on behalf of Acade ´mie des sciences. R E ´S U M E Ĺestransporteurs d'oxyge `ne a `base d'he ´moglobine (HBOCs) peuvent induire stress oxydant, vasoconstriction et inflammation. Afin de re ´duire ces proprie ´te ´s vasoactives inde ´sirables, nous avons augmente ´, par ge ´nie ge ´ne ´tique, la taille mole ´culaire de l'he ´moglobine (Hb) produisant une Hb octame ´rique recombinante (r), la rHbbG83C. La rHbbG83C n'a pas d'impact sur la viabilite ´des cellules endothe ´liales et induit une re ´pression tre `s importante de la transcription du ge `ne de la NO synthase (marqueur de Abbreviations: HBOCs, hemoglobin-based oxygen carriers; Dex-BTC-Hb, human Hb conjugated to dextran benzene tetracarboxylate macromolecules; eNOS, endothelial nitric oxide synthase; ICAM-1, intermolecular-adhesion molecule 1; HUVEC, human umbilical vein endothelial cells; PS, phosphatidylserine; PI, propidium iodide; HO, heme oxygenase.

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Recombinant Octameric Hemoglobins as Resuscitation Fluids in a Murine Model of Traumatic Brain Injury Plus Hemorrhagic Shock

Cited by 2 publications

References 56 publications

Autoxidation and Oxygen Binding Properties of Recombinant Hemoglobins with Substitutions at the αVal-62 or βVal-67 Position of the Distal Heme Pocket

Autoxidation and Oxygen Binding Properties of Recombinant Hemoglobins with Substitutions at the αVal-62 or βVal-67 Position of the Distal Heme Pocket

Interaction of recombinant octameric hemoglobin with endothelial cells

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