PMID- 14615383
OWN - NLM
STAT- MEDLINE
DCOM- 20040415
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 103
IP  - 6
DP  - 2004 Mar 15
TI  - Expression of HbC and HbS, but not HbA, results in activation of K-Cl cotransport 
      activity in transgenic mouse red cells.
PG  - 2384-90
AB  - Elevation of K-Cl cotransport in patients with homozygous hemoglobin (Hb) S or 
      HbC increases red cell mean corpuscular hemoglobin concentration (MCHC) and 
      contributes significantly to pathology. Elucidation of the origin of elevated 
      K-Cl cotransport in red cells with mutant hemoglobins has been confounded by the 
      concomitant presence of reticulocytes with high K-Cl cotransport. In red cells of 
      control mice (C57BL), transgenic mice that express only human HbA, and transgenic 
      mice that express both mouse globins and human HbS, volume stimulation is weak 
      and insensitive to NO3- and dihydroindenyl-oxy-alkanoic acid (DIOA). DIOA and 
      NO3- are inhibitors in all other mammalian red cells. In contrast, in knock-out 
      mice expressing exclusively human hemoglobin HbC or HbS+ gamma, replacement of 
      isotonic Cl- media by hypotonic Cl- resulted in strong volume stimulation and 
      sensitivity to DIOA, okadaic acid, and NO3-. In summary, we find that HbC, under 
      all conditions, and HbS+ gamma, in the absence of mouse globins, have significant 
      quantitative and qualitative effects on K-Cl cotransport in mouse red cells and 
      activate mouse K-Cl. We conclude that human globins are able to stimulate the 
      activity and/or regulation of K-Cl cotransport in mouse red cells. These 
      observations support the contention that HbS and HbC stimulate K-Cl cotransport 
      in human red cells.
FAU - Romero, Jose R
AU  - Romero JR
AD  - Division of Endocrinology, Diabetes and Hypertension, Harvard Medical School, 
      Boston, MA, USA.
FAU - Suzuka, Sandra M
AU  - Suzuka SM
FAU - Nagel, Ronald L
AU  - Nagel RL
FAU - Fabry, Mary E
AU  - Fabry ME
LA  - eng
GR  - 1M01RR12248/RR/NCRR NIH HHS/United States
GR  - DK02817/DK/NIDDK NIH HHS/United States
GR  - P01HL55435/HL/NHLBI NIH HHS/United States
GR  - P60HL38655/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20031113
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (((dihydroindenyl)oxy)alkanoic acid)
RN  - 0 (Carboxylic Acids)
RN  - 0 (Chlorides)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hemoglobin, Sickle)
RN  - 0 (Hypotonic Solutions)
RN  - 0 (Indenes)
RN  - 0 (Nitrates)
RN  - 1W21G5Q4N2 (Okadaic Acid)
RN  - 9008-00-8 (Hemoglobin C)
RN  - 9034-51-9 (Hemoglobin A)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - Animals
MH  - Biological Transport/drug effects/physiology
MH  - Carboxylic Acids/pharmacology
MH  - Chlorides/*metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Erythrocytes/*metabolism
MH  - Hemoglobin A/genetics
MH  - Hemoglobin C/*genetics
MH  - Hemoglobin, Sickle/*genetics
MH  - Humans
MH  - Hypotonic Solutions/pharmacology
MH  - Indenes/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Nitrates/pharmacology
MH  - Okadaic Acid/pharmacology
MH  - Potassium/*metabolism
EDAT- 2003/11/15 05:00
MHDA- 2004/04/16 05:00
CRDT- 2003/11/15 05:00
PHST- 2003/11/15 05:00 [pubmed]
PHST- 2004/04/16 05:00 [medline]
PHST- 2003/11/15 05:00 [entrez]
AID - S0006-4971(20)50038-4 [pii]
AID - 10.1182/blood-2003-01-0237 [doi]
PST - ppublish
SO  - Blood. 2004 Mar 15;103(6):2384-90. doi: 10.1182/blood-2003-01-0237. Epub 2003 Nov 
      13.