Effects of 5-hydroxymethyl-2-furfural on the volume and membrane permeability of red blood cells from patients with sickle cell disease
The Journal of Physiology
Wiley on behalf of the Physiological Society
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Hannemann, A., Cytlak, U. M., Rees, D. C., Tewari, S., & Gibson, J. (2014). Effects of 5-hydroxymethyl-2-furfural on the volume and membrane permeability of red blood cells from patients with sickle cell disease. The Journal of Physiology, 592 4039-4049. https://doi.org/10.1113/jphysiol.2014.277681
The heterocyclic aldehyde 5-hydroxymethyl-2-furfural (5HMF) interacts allosterically with HbS in red blood cells (RBCs) from patients with sickle cell disease (SCD), thereby increasing oxygen affinity and decreasing HbS polymerisation and RBC sickling during hypoxia. We hypothesise that should 5HMF also inhibit the main cation pathways implicated in dehydration of RBCs from SCD patients - the deoxygenation-induced cation pathway (Psickle), the Ca2+-activated K+ channel (the Gardos channel) and the K+-Cl- cotransporter (KCC) - it would have a synergistic effect in protection against sickling, directly through interacting with HbS, and indirectly through maintaining hydration and reducing [HbS]. This study was therefore designed to investigate the effects of 5HMF on RBC volume and K+ permeability in vitro. 5HMF markedly reduced the deoxygenation-induced dehydration of RBCs whether in response to maintained deoxygenation or to cyclical deoxygenation / re-oxygenation. 5HMF was found to inhibit Psickle, an effect which correlated with its effects on sickling. Deoxygenation-induced activation of the Gardos channel and exposure of phosphatidylserine were also inhibited, probably indirectly via reduced entry of Ca2+ through the Psickle pathway. Effects of 5HMF on KCC were more modest with a slight inhibition in N¬-ethylmaleimide (NEM, 1 mM) -treated RBCs and stimulation in RBCs untreated with NEM. These findings support the hypothesis that 5HMF may also be beneficial through effects on RBC ion and water homeostasis.
Sickle, red blood cells, heterocyclic aldehydes, 5-hydroxymethyl-2-furfural, volume - potassium permeability
We thank Action Medical Research and the MRC for financial support. UMC receives a BBSRC studentship.
External DOI: https://doi.org/10.1113/jphysiol.2014.277681
This record's URL: https://www.repository.cam.ac.uk/handle/1810/247869