Format

Send to

Choose Destination
See comment in PubMed Commons below
Blood Cells Mol Dis. 2014 Jun-Aug;53(1-2):21-6. doi: 10.1016/j.bcmd.2014.02.004. Epub 2014 Mar 1.

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

Author information

  • 1Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, CB3 0ES, United Kingdom.
  • 2Department of Paediatric Haematology, King's College London School of Medicine, King's College Hospital NHS Foundation Trust, Denmark Hill, London, SE5 9RS, United Kingdom.
  • 3Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, CB3 0ES, United Kingdom. Electronic address: jsg1001@cam.ac.uk.

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.

Copyright © 2014. Published by Elsevier Inc.

KEYWORDS:

Aromatic aldehydes; Potassium permeability; Red blood cells; Sickle; o-Vanillin

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk