TY - JOUR
T1 - Effects of 5-hydroxymethyl-2-furfural on the volume and membrane permeability of red blood cells from patients with sickle cell disease
AU - Hannemann, Anke
AU - Cytlak, Urszula M.
AU - Rees, David C.
AU - Tewari, Sanjay
AU - Gibson, John S.
N1 - Publisher Copyright:
© 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84907877340&partnerID=8YFLogxK
U2 - 10.1113/jphysiol.2014.277681
DO - 10.1113/jphysiol.2014.277681
M3 - Article
C2 - 25015917
AN - SCOPUS:84907877340
SN - 0022-3751
VL - 592
SP - 4039
EP - 4049
JO - Journal of Physiology
JF - Journal of Physiology
IS - 18
ER -