Thyroid hormone specifically regulates skeletal muscle Na(+)-K(+)-ATPase alpha 2- and beta 2-isoforms.
The purpose of this study was to determine the pattern of thyroid hormone (triiodothyronine, T3) regulation of the Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) alpha- and beta-subunit expression in skeletal muscle, which expresses alpha 1-, alpha 2-, beta 1-, and beta 2-subunits, and compare it with that seen in kidney, which expresses only alpha 1 and beta 1. Three steady states were studied: hypothyroid, euthyroid, and hyperthyroid (hypothyroids injected daily with 1 microgram T3/g body wt for 2-16 days). Protein and mRNA abundance, determined by Western and Northern analysis, were normalized to a constant amount of homogenate protein and total RNA, respectively. In skeletal muscle, there was no change in alpha 1- or beta 1-mRNA or protein levels in the transition from hypothyroid to hyperthyroid. However, alpha 2 was highly regulated; mRNA reached a new steady-state level of fivefold over hypothyroid by 8 days of T3 treatment and protein abundance increased threefold. In addition, beta 2-mRNA and protein were detected in skeletal muscle and were also highly regulated by T3; beta 2-mRNA increased nearly fourfold over hypothyroid level, and beta 2-protein abundance increased over twofold. In kidney in the transition from hypothyroid to hyperthyroid, there were coordinate 1.6-fold increases in both alpha 1- and beta 1-mRNA abundance that predicted the observed changes in alpha 1- and beta 1-protein levels and Na(+)-K(+)-ATPase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Azuma
K K
KK
Department of Physiology and Biophysics, University of Southern California School of Medicine, Los Angeles 90033.
Hensley
C B
CB
Tang
M J
MJ
McDonough
A A
AA
D000818:Animals; D001921:Brain / Q000201:enzymology; D015151:Immunoblotting; D007527:Isoenzymes / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology; D008297:Male; D009132:Muscles / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014284:Triiodothyronine / Q000494:pharmacology / Q000502:physiology*
D007527:Isoenzymes; D012333:RNA, Messenger; D014284:Triiodothyronine; D000254:Sodium-Potassium-Exchanging ATPase