Fiber-specific regulation by thyroid hormone of sarcoplasmic
reticulum ca2+-atpase isoform expression in rat skeletal muscle.
Linden, C. Gerard Van Der, Warner S. Simonides, Alice Muller, Willem
J. Van Der Laarse, Jacqueline L. Vermeulen, Marian J. Zuidwijk,
Antoon F. Moorman, Cornelis Van Hardeveld.
Department of Anatomy and Embryology, University of Amsterdam,
Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The
Netherlands
APStracts 3:0219C, 1996.
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 Ca2+-ATPase isoforms, SERCA1 and SERCA2a, respectively, and
total SR Ca2+-ATPase activity in rat skeletal muscle. Cross-sections
and homogenates of soleus (SOL) and extensor digitorum longus (EDL)
muscles from hypo-, eu-, and hyperthyroid rats were examined and
expression of Ca2+-ATPase isoforms in individual fibers was compared
with that 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 phenotype in half of the fibers that were slow
in the absence of T3. The conversion was partial in the other half,
giving rise to a mixed phenotype. The stimulation by T3 of total
SERCA expression in all fibers was reflected by increased SR Ca2+
-ATPase activity. The time course of the T3-induced changes of SERCA
isoform expression was examined between day 1 and 14 following the
start of daily T3 treatment of euthyroid rats. SERCA1 expression was
stimulated by T3 at a pre-translational level in all fibers. SERCA2a
mRNA expression was transiently stimulated and disappeared in a
subset of fibers. In these fibers SR Ca2+-ATPase activity was high
due to high SERCA1 protein levels. These data suggest that the
ultimate down regulation of SERCA2a expression, which is always
associated with high SR Ca2+-ATPase activities, occurs at a pre
-translational level.
Received 21 February 1996; accepted in final form 25 June 1996.
APS Manuscript Number C94-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996