Fiber-specific regulation of Ca(2+)-ATPase isoform expression by thyroid hormone in rat skeletal muscle.
We studied the effect of thyroid hormone (3,5,3'-triiodo-L-thyronine, T3) on the expression of sarcoplasmic reticulum (SR) fast- and slow-type Ca(2+)-ATPase isoforms, SERCA1 and SERCA2a, respectively, and total SR Ca(2+)-ATPase activity in rat skeletal muscle. Cross sections and homogenates of soleus and extensor digitorum longus muscles from hypo-, eu-, and hyperthyroid rats were examined, and expression of Ca(2+)-ATPase isoforms in individual fibers was compared with expression of fast (MHC II) and slow (MHC I) myosin heavy chain isoforms. In both muscles, T3 induced a coordinated and full conversion to a fast-twitch phenotype in one-half of the fibers that were slow twitch in the absence of T3. The conversion was partial in the other one-half of the fibers, giving rise to a mixed phenotype. The stimulation by T3 of total SERCA expression in all fibers was reflected by increased SR Ca(2+)-ATPase activity. The time course of the T3-induced changes of SERCA isoform expression was examined 1-14 days after the start of daily T3 treatment of euthyroid rats. SERCA1 expression was stimulated by T3 at a pretranslational level in all fibers. SERCA2a mRNA expression was transiently stimulated and disappeared in a subset of fibers. In these fibers SR Ca(2+)-ATPase activity was high because of high SERCA1 protein levels. These data suggest that the ultimate downregulation of SERCA2a expression, which is always associated with high SR Ca(2+)-ATPase activities, occurs at a pretranslational level.
van der Linden
C G
CG
Laboratory for Physiology, Institute for Cardiovascular Research, Vrije Universiteit, Amsterdam, The Netherlands.
Simonides
W S
WS
Muller
A
A
van der Laarse
W J
WJ
Vermeulen
J L
JL
Zuidwijk
M J
MJ
Moorman
A F
AF
van Hardeveld
C
C
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000096:biosynthesis*; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000201:enzymology*; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000648:ultrastructure; D018995:Myosin Heavy Chains / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013963:Thyroid Hormones / Q000494:pharmacology*
D007527:Isoenzymes; D013963:Thyroid Hormones; D018995:Myosin Heavy Chains; D000252:Calcium-Transporting ATPases