Effects of 5-hydroxymethyl-2-furfural on the volume and membrane permeability of red blood cells from patients with sickle cell disease

Anke Hannemann, Urszula M. Cytlak, David C. Rees, Sanjay Tewari, John S. Gibson

Research output: Contribution to journalArticlepeer-review

Abstract

The heterocyclic aldehyde 5-hydroxymethyl-2-furfural (5HMF) interacts allosterically with the abnormal formof haemoglobin (Hb), HbS, in red blood cells (RBCs) frompatients with sickle cell disease (SCD), thereby increasing oxygen affinity and decreasing HbS polymerization andRBCsickling during hypoxia.We hypothesized that should5HMFalso inhibit the main cation pathways implicated in the 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 interactingwith 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.

Original languageEnglish
Pages (from-to)4039-4049
Number of pages11
JournalJournal of Physiology
Volume592
Issue number18
DOIs
Publication statusPublished - 2014

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre

Fingerprint

Dive into the research topics of 'Effects of 5-hydroxymethyl-2-furfural on the volume and membrane permeability of red blood cells from patients with sickle cell disease'. Together they form a unique fingerprint.

Cite this