title: Effects of o-vanillin on K⁺ transport of red blood cells from patients with sickle cell disease.
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 Ca(2+)-activated K(+) channel (or Gardos channel) were inhibited with IC50 of about 0.3 and 1 mM, respectively, with activities almost completely abolished by 5 mM. Similar effects were observed in RBCs treated with the thiol reacting reagent N-ethylmaleimide or with the Ca(2+) ionophore A23187, to circumvent any action via HbS polymerisation. The deoxygenation-induced cation conductance (sometimes termed P(sickle)) 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.
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, CB3 0ES, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Hannemann
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, CB3 0ES, United Kingdom.
authors.forename: U M C
authors.initials: UM
authors.lastname: Cytlak
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, CB3 0ES, United Kingdom.
authors.forename: O T
authors.initials: OT
authors.lastname: Gbotosho
authors.affiliation: Department of Paediatric Haematology, King's College London School of Medicine, King's College Hospital NHS Foundation Trust, Denmark Hill, London, SE5 9RS, United Kingdom.
authors.forename: D C
authors.initials: DC
authors.lastname: Rees
authors.affiliation: Department of Paediatric Haematology, King's College London School of Medicine, King's College Hospital NHS Foundation Trust, Denmark Hill, London, SE5 9RS, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Tewari
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, CB3 0ES, United Kingdom. Electronic address: jsg1001@cam.ac.uk.
authors.forename: J S
authors.initials: JS
authors.lastname: Gibson
mesh_terms: D000755:Anemia, Sickle Cell / Q000235:genetics / Q000378:metabolism*; D001547:Benzaldehydes / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D006451:Hemoglobin, Sickle / Q000235:genetics; D006720:Homozygote; D006801:Humans; D011188:Potassium / Q000378:metabolism*; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D027981:Symporters / Q000378:metabolism; D000096922:K Cl- Cotransporters
chemical_list: D001547:Benzaldehydes; D000001:Calcimycin; D006451:Hemoglobin, Sickle; D011188:Potassium; D028021:Sodium-Potassium-Chloride Symporters; D027981:Symporters; D000096922:K Cl- Cotransporters; C060843:2-vanillin
keywords: Aromatic aldehydes; Potassium permeability; Red blood cells; Sickle; o-Vanillin