Modulation of erythrocyte potassium chloride cotransport, potassium content, and density by dietary magnesium intake in transgenic SAD mouse.
Prevention of erythrocyte dehydration is a potential therapeutic strategy for sickle cell disease. Increasing erythrocyte magnesium (Mg) could inhibit sickle cell dehydration by increasing chloride (CI) and water content and by inhibiting potassium chloride (K-CI) cotransport. In transgenic SAD 1 and (control) C57BL/6 normal mice, we investigated the effect of 2 weeks of diet with either low Mg (6 +/- 2 mg/kg body weight/d) or high Mg (1,000 +/- 20 mg/kg body weight/ d), in comparison with a diet of standard Mg (400 +/- 20 mg/ kg body weight/d). The high-Mg diet increased SAD 1 erythrocyte Mg and K contents and reduced K-CI cotransport activity, mean corpuscular hemoglobin concentration (MCHC), cell density, and reticulocyte count. SAD 1 mice treated with low-Mg diet showed a significant reduction in erythrocyte Mg and K contents and increases in K-CI cotransport, MCHC, cell density, and reticulocyte counts. In SAD 1 mice, hematocrit (Hct) and hemoglobin (Hb) decreased significantly with low Mg diet and increased significantly with high-Mg diet. The C57BL/6 controls showed significant changes only in erythrocyte Mg and K content, and K-CI cotransport activities, similar to those observed in SAD 1 mice. Thus, in the SAD 1 mouse, changes in dietary Mg modulate K-CI cotransport, modify erythrocyte dehydration, and ultimately affect Hb levels.
De Franceschi
L
L
Department of Internal Medicine, University of Verona, Italy.
Beuzard
Y
Y
Jouault
H
H
Brugnara
C
C
D000755:Anemia, Sickle Cell / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002352:Carrier Proteins / Q000097:blood*; D002712:Chlorides / Q000097:blood*; D004032:Diet; D004195:Disease Models, Animal; D004913:Erythrocytes, Abnormal / Q000737:chemistry / Q000187:drug effects*; D005260:Female; D006400:Hematocrit; D006451:Hemoglobin, Sickle / Q000737:chemistry / Q000235:genetics; D006454:Hemoglobins / Q000032:analysis; D008274:Magnesium / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D008275:Magnesium Deficiency / Q000097:blood / Q000150:complications; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009996:Osmotic Fragility / Q000187:drug effects; D011188:Potassium / Q000097:blood*; D017701:Reticulocyte Count / Q000187:drug effects; D027981:Symporters; D000096922:K Cl- Cotransporters
D002352:Carrier Proteins; D002712:Chlorides; D006451:Hemoglobin, Sickle; D006454:Hemoglobins; D008274:Magnesium; D011188:Potassium; D027981:Symporters; D000096922:K Cl- Cotransporters