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Am J Physiol Cell Physiol 269: C899-C906, 1995;
0363-6143/95 $5.00
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AJP - Cell Physiology, Vol 269, Issue 4 C899-C906, Copyright © 1995 by American Physiological Society

ARTICLES

Sulfhydryl oxidation and activation of red cell K(+)-Cl- cotransport in the transgenic SAD mouse

L. De Franceschi, Y. Beuzard and C. Brugnara
Department of Internal Medicine, University of Verona, Italy.

The SAD mouse is characterized by the expression of human SAD hemoglobin (Hb), a super S Hb with a higher tendency to polymerize than HbS due to the presence of two additional mutations, Antilles beta 23Ile and D Punjab beta 121Glu. Monovalent cation transport was studied in erythrocytes from SAD-1 (Hb SAD = 19%) and beta-thal/SAD-1 (Hb SAD = 26%) mice. Erythrocytes containing Hb SAD exhibited dehydration, increased maximal rate of Na(+)-K+ pump, unchanged Rb+ flux via the Gardos channel, and increased K(+)-Cl- cotransport. K(+)-Cl- cotransport was defined as Cl(-)-dependent (substitution with sulfamate or methanesulfonate) okadaic acid-sensitive K+ efflux. Volume regulatory decrease via K(+)-Cl- cotransport was also increased in swollen SAD erythrocytes compared with controls. K(+)-Cl- cotransport was stimulated by staurosporine in all mouse strains, but the extent of stimulation was reduced in beta-thal/SAD-1 mice. Treatment with dithiothreitol reduced K(+)-Cl- cotransport activity in SAD-1 and beta-thal/SAD-1 mice to levels similar to that of control strains, indicating that reversible sulfhydryl oxidation contributes to the activated state of K(+)-Cl- cotransport in mouse erythrocytes that express transgenic human Hb SAD.


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L. De Franceschi, C. Brugnara, P. Rouyer-Fessard, H. Jouault, and Y. Beuzard
Formation of Dense Erythrocytes in SAD Mice Exposed to Chronic Hypoxia: Evaluation of Different Therapeutic Regimens and of a Combination of Oral Clotrimazole and Magnesium Therapies
Blood, December 15, 1999; 94(12): 4307 - 4313.
[Abstract] [Full Text] [PDF]


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