Interaction of recombinant octameric hemoglobin with endothelial cells.
Fiche publication
Date publication
février 2015
Journal
Comptes rendus biologies
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MENU Patrick
Tous les auteurs :
Gaucher C, Domingues-Hamdi É, Prin-Mathieu C, Menu P, Baudin-Creuza V
Lien Pubmed
Résumé
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) HbβG83C. We investigate the potential side effects of rHbβG83C on endothelial cells. The rHbβG83C 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 rHbβG83C, 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 βG83C mutant, leads to little impact at the level of endothelial cell inflammatory response and thus appears as an interesting molecule for HBOC development.
Mots clés
Biomarkers, Blood Substitutes, pharmacology, Cell Survival, drug effects, Dextrans, pharmacology, Down-Regulation, drug effects, Drug Evaluation, Preclinical, E-Selectin, biosynthesis, Gene Expression Regulation, drug effects, Heme Oxygenase-1, biosynthesis, Hemoglobins, analysis, Human Umbilical Vein Endothelial Cells, drug effects, Humans, Hydroxyethyl Starch Derivatives, pharmacology, Inflammation, chemically induced, Intercellular Adhesion Molecule-1, biosynthesis, Methemoglobin, analysis, Models, Molecular, Nitric Oxide Synthase Type III, biosynthesis, Oxidative Stress, drug effects, Plasma Substitutes, pharmacology, Protein Conformation, Real-Time Polymerase Chain Reaction, Vasoconstriction, drug effects
Référence
C. R. Biol.. 2015 Feb;338(2):95-102