Modulation of serca2 expression by thyroid hormone and
norepinephrine in cardiocytes. the role of contractility..
Muller, Alice, Marian J. Zuidwijk, Warner S. Simonides, and Cornelis
Van Hardeveld.
Laboratory for Physiology, Institute for Cardiovascular Research
(ICaR-VU), Vrije Universiteit, Van der Boechorststraat 7, 1081 BT
Amsterdam, The Netherlands
APStracts 3:0474H, 1996.
Decreased expression of the sarcoplasmic reticulum Ca2&-ATPase
(SERCA2), a major determinant of Ca2&-homeostasis, contributes to
the abnormal intracellular Ca2&-handling in the failing heart. We
investigated the contractility-dependency of the effects of
norepinephrine (NE) and thyroid hormone (T3) on SERCA2 expression in
cultured neonatal heart cells under serum-free conditions. NE and T3
are associated with pathological and physiological forms of
hypertrophy, respectively, whereas both hormones increase
contractility. In contracting cultures, T3 increased SERCA2 protein
and mRNA levels by 35% and 110%, respectively. The same stimulatory
effects of T3 on SERCA2 expression were found in contraction-arrested
cells. In contracting cultures, NE induced a decrease of SERCA2
protein and mRNA levels by 40% and 60%, respectively. In contrast,
SERCA2 protein and mRNA levels were not decreased by NE in
contraction-arrested cells, indicating that contractility is a
prerequisite for the negative influence of NE on SERCA2 expression.
Electrical stimulation at a fixed frequency in the presence and
absence of NE demonstrated that the NE-induced increase in
contraction-frequency is unlikely to account for the decreased SERCA2
expression induced by NE. The results suggest that the effect of
contractility on SERCA2 expression depends on the signal transduction
pathways that are activated by NE and T3.
Received 21 October 1996; accepted in final form 13 February
1996.
APS Manuscript Number H145-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996