Sulfhydryl oxidation and activation of red cell k-cl cotransport in
the sad mouse, a transgenic model for sickle cell anemia.
Franceschi, Lucia De, Yves Beuzard, and Carlo Brugnara.
Department of Internal Medicine, University of Verona, 37134 Italy;
INSERM Unit 91, Hospital H. Mondor, Creteil, 94010 France,
Departments of Laboratory Medicine and Pathology, The Children's
Hospital, Harvard Medical School, Boston, MA 02115, USA.
APStracts 2:0187C, 1995.
The SAD mouse is characterized by the expression of human SAD Hb, a
super S hemoglobin with a higher tendency to polymerize than Hb S due
to the presence of two additional mutations, Antilles, 23Ile and D
Punjab, 121Glu. Monovalent cation transport was studied in
erythrocytes from SAD 1 (Hb SAD = 19%) and 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
chloride-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
to controls. K-Cl cotransport was stimulated by staurosporine in all
mouse strains, but the extent of stimulation was reduced in thal/SAD
1 mice. Treatment with dithiothreitol (DTT) reduced K-Cl cotransport
activity in SAD 1 and thal/SAD 1 mouse 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 which express transgenic human Hb SAD.
Received 18 January 1995; accepted in final form 2 May 1995.
APS Manuscript Number C36-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 9 May 1995.