Effect of thyroid hormone on the distribution and activity of Na, K-ATPase in ventricular myocardium.
Employing detergent-free sucrose-density gradient fractionation method we isolated cholesterol-rich lighter membrane fractions containing approximately 10% of protein, approximately 30% of cholesterol in membranes of ventricular myocardium. Cholesterol-rich lighter membrane fractions contain >70% of Na, K-ATPase and caveolins 1 and 3 and <10% of beta-actin. Treatment of hypothyroid rats with T(3) increased the relative abundance of both alpha1 and beta1 Na, K-ATPase subunits in total membranes by 4- to 5-fold (with no change in caveolin-3), and resulted in 1.9-fold increase in enzyme activity. T(3)-induced Na, K-ATPase subunits were preferentially distributed to the lighter fractions (#s 4, 5 and 6); and increased abundance of alpha1 and beta1 were 34-70% and 43-68%, respectively. We conclude that the activity of Na, K-ATPase is not uniform in cardiac membranes, and while a significant amount of Na, K-ATPase is present in cardiac cholesterol-rich membrane fractions, the intrinsic activity is significantly less than the enzyme present in relatively cholesterol-poor membranes.
Kasturi
Sriram
S
Division of Clinical and Molecular Endocrinology, Department of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4951, USA.
Ismail-Beigi
Faramarz
F
D000199:Actins / Q000032:analysis; D000818:Animals; D051242:Caveolin 1 / Q000032:analysis; D051244:Caveolin 3 / Q000032:analysis; D002458:Cell Fractionation; D002784:Cholesterol / Q000032:analysis; D006352:Heart Ventricles / Q000201:enzymology; D006980:Hyperthyroidism / Q000139:chemically induced; D007037:Hypothyroidism / Q000139:chemically induced; D009206:Myocardium / Q000201:enzymology*; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis / Q000378:metabolism*; D013963:Thyroid Hormones / Q000494:pharmacology*; D013974:Thyroxine; D014018:Tissue Distribution; D014284:Triiodothyronine / Q000494:pharmacology; D014498:Uracil / Q000031:analogs & derivatives / Q000494:pharmacology
D000199:Actins; D051242:Caveolin 1; D051244:Caveolin 3; D013963:Thyroid Hormones; D014284:Triiodothyronine; C056698:6-n-propyluracil; D014498:Uracil; D002784:Cholesterol; D000254:Sodium-Potassium-Exchanging ATPase; D013974:Thyroxine