Sulfhydryl oxidation and activation of red cell K(+)-Cl- cotransport in the transgenic SAD mouse.
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.
D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002352:Carrier Proteins / Q000097:blood*; D002412:Cations / Q000097:blood; D004229:Dithiothreitol / Q000494:pharmacology; D004351:Drug Resistance; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism*; D006451:Hemoglobin, Sickle / Q000235:genetics*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010042:Ouabain / Q000494:pharmacology; D010084:Oxidation-Reduction; D011188:Potassium / Q000097:blood; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D027981:Symporters; D000096922:K Cl- Cotransporters
D002034:Bumetanide; D002352:Carrier Proteins; D002412:Cations; D004229:Dithiothreitol; D006451:Hemoglobin, Sickle; D010042:Ouabain; D011188:Potassium; D013438:Sulfhydryl Compounds; D027981:Symporters; D000096922:K Cl- Cotransporters; C070168:hemoglobin SAD