Effects of o-vanillin on K+ transport of red blood cells from patients with sickle cell disease

A. Hannemann, U. M.C. Cytlak, O. T. Gbotosho, D. C. Rees, S. Tewari, J. S. Gibson

Research output: Contribution to journalArticlepeer-review

Abstract

Aromatic aldehydes like o-vanillin were designed to reduce the complications of sickle cell disease (SCD) by interaction with HbS, to reduce polymerisation and RBC sickling. Present results show that o-vanillin also directly affects RBC membrane permeability. Both the K+-Cl- cotransporter (KCC) and the Ca2+-activated K+ channel (or Gardos channel) were inhibited with IC50 of about 0.3 and 1mM, respectively, with activities almost completely abolished by 5mM. Similar effects were observed in RBCs treated with the thiol reacting reagent N-ethylmaleimide or with the Ca2+ ionophore A23187, to circumvent any action via HbS polymerisation. The deoxygenation-induced cation conductance (sometimes termed Psickle) was partially inhibited, whilst deoxygenation-induced exposure of phosphatidylserine was completely abrogated. Na+/K+ pump activity was also reduced. Notwithstanding, o-vanillin stimulated K+ efflux through an unidentified pathway and resulted in reduction in cell volume (as measured by wet weight-dry weight). These actions are relevant to understanding how aromatic aldehydes may affect RBC membrane permeability per se as well as HbS polymerisation and thereby inform design of compounds most efficacious in ameliorating the complications of SCD.

Original languageEnglish
Pages (from-to)21-26
Number of pages6
JournalBlood Cells, Molecules, and Diseases
Volume53
Issue number1-2
DOIs
Publication statusPublished - Jun 2014

Keywords

  • Aromatic aldehydes
  • O-Vanillin
  • Potassium permeability
  • Red blood cells
  • Sickle

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