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

Abstract

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.

• Authors: L De Franceschi, Y Beuzard, C Brugnara
• Journal: The American journal of physiology (Am J Physiol) Vol. 269 Issue 4 Pt 1 Pg. C899-906 (Oct 1995) ISSN: 0002-9513 [Print] United States
• PMID: 7485459 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Carrier Proteins
• Cations
• Hemoglobin, Sickle
• Sulfhydryl Compounds
• Symporters
• hemoglobin SAD
• potassium-chloride symporters
• Bumetanide
• Ouabain
• Potassium
• Dithiothreitol

Topics

• Animals
• Bumetanide (pharmacology)
• Carrier Proteins (blood)
• Cations (blood)
• Dithiothreitol (pharmacology)
• Drug Resistance
• Erythrocytes (cytology, metabolism)
• Hemoglobin, Sickle (genetics)
• Humans
• Mice
• Mice, Transgenic
• Ouabain (pharmacology)
• Oxidation-Reduction
• Potassium (blood)
• Sulfhydryl Compounds (metabolism)
• Symporters