Glucocorticoids increase sodium pump alpha(2)- and beta(1)-subunit abundance and mRNA in rat skeletal muscle.
Fourteen-day adrenal steroid treatment increases [(3)H]ouabain binding sites 22-48% in muscle biopsies from patients treated with adrenal steroids for chronic obstructive lung disease and in rats treated with dexamethasone (Dex). Ouabain binding measures plasma membrane sodium pumps (Na(+)-K(+)-ATPase) with isoform-dependent affinity. In this study we have established the specific pattern of Dex regulation of sodium pump isoform protein and mRNA levels in muscle. Rats were infused with Dex (0.1 mg/kg per day) or vehicle for 14 days. Abundance of sodium pump catalytic alpha(1)- and alpha(2)-subunits and glycoprotein beta(1)- and beta(2)-subunits was determined by immunoblot in soleus, extensor digitorum longus, whole gastrocnemius, and diaphragm and was normalized to the mean vehicle control value. Dex increased alpha(2) and beta(1) protein in all muscle types by 53-78% and ~50%, respectively. Dex increased alpha(1) protein only in diaphragm (65 +/- 7%). At the mRNA level in whole hindlimb muscle, Dex increased alpha(2) (6.4 +/- 0.5-fold) and beta(1) (1.54 +/- 0.15-fold) and decreased beta(2) (to 0.36 +/- 0.6 of control). In summary, alpha(2)beta(1) is the Dex-responsive pump in all skeletal muscles, and changes in alpha(2) and beta(1) mRNA levels can drive the 50% change in alpha(2)beta(1)-subunits, which can account for the reported increase in [(3)H]ouabain binding.
Thompson
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CB
Department of Physiology and Biophysics, University of Southern California School of Medicine, Los Angeles, California 90089, USA.
Dorup
I
I
Ahn
J
J
Leong
P K
PK
McDonough
A A
AA
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics* / Q000378:metabolism*
D005938:Glucocorticoids; D007527:Isoenzymes; D012333:RNA, Messenger; D003907:Dexamethasone; D000254:Sodium-Potassium-Exchanging ATPase