PMID- 15242872
OWN - NLM
STAT- MEDLINE
DCOM- 20041214
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 104
IP  - 9
DP  - 2004 Nov 1
TI  - KCl cotransport mediates abnormal sulfhydryl-dependent volume regulation in 
      sickle reticulocytes.
PG  - 2954-60
AB  - KCl cotransport (KCC) activation by cell swelling and pH was compared in sickle 
      (SS) and normal (AA) red blood cells (RBCs). KCC fluxes had the same relationship 
      to mean corpuscular hemoglobin concentration (MCHC) in SS and AA RBCs when 
      normalized to the maximal volume-stimulated (VS(max)) flux (MCHC < 270 g/L [27 
      g/dL]). Acid-stimulated (pH 6.9) KCC flux in SS RBCs was 60% to 70% of VS(max) 
      KCC versus 20% in AA RBCs. Density gradients were used to track changes in 
      reticulocyte MCHC during KCC-mediated regulatory volume decrease (RVD). Swelling 
      to MCHC of 260 g/L (26 g/dL) produced Cl-dependent RVD that resulted in higher 
      MCHC in SS than AA reticulocytes. In acid pH, RVD was also greater in SS than AA 
      reticulocytes. Sulfhydryl reduction by dithiothreitol (DTT) lowered VS(max) KCC 
      flux in AA and SS RBCs by one third but did not alter swelling-induced RVD. DTT 
      lowered acid-activated KCC in SS RBCs by 50% and diminished acid-induced RVD in 
      SS reticulocytes. Thus, swelling activation of KCC is normal in SS RBCs but 
      KCC-mediated RVD produces higher MCHC in SS than AA reticulocytes. Acid 
      activation of KCC is exaggerated in SS RBCs and causes dehydration in SS 
      reticulocytes. KCC response to acid stimulation was mitigated by DTT, suggesting 
      that it arises from sulfhydryl oxidation.
FAU - Joiner, Clinton H
AU  - Joiner CH
AD  - Cincinnati Comprehensive Sickle Cell Center, Children's Hospital Medical Center, 
      3333 Burnet Ave, Cincinnati, OH 45229-3039, USA. clint.joiner@cchmc.org
FAU - Rettig, R Kirk
AU  - Rettig RK
FAU - Jiang, Maorong
AU  - Jiang M
FAU - Franco, Robert S
AU  - Franco RS
LA  - eng
GR  - U54 HL70871/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040708
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Sulfhydryl Compounds)
RN  - 0 (Symporters)
RN  - 660YQ98I10 (Potassium Chloride)
RN  - T8ID5YZU6Y (Dithiothreitol)
SB  - IM
MH  - Anemia, Sickle Cell/*pathology
MH  - Biological Transport
MH  - *Cell Size/drug effects
MH  - Cells, Cultured
MH  - Dithiothreitol/pharmacology
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Kinetics
MH  - Oxidation-Reduction
MH  - Potassium Chloride/*metabolism
MH  - Reticulocytes/drug effects/*pathology
MH  - Sulfhydryl Compounds/*physiology
MH  - Symporters/*metabolism
EDAT- 2004/07/10 05:00
MHDA- 2004/12/16 09:00
CRDT- 2004/07/10 05:00
PHST- 2004/07/10 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/07/10 05:00 [entrez]
AID - S0006-4971(20)55972-7 [pii]
AID - 10.1182/blood-2004-01-0112 [doi]
PST - ppublish
SO  - Blood. 2004 Nov 1;104(9):2954-60. doi: 10.1182/blood-2004-01-0112. Epub 2004 Jul 
      8.