Regulation of myocardial Ca2+-ATPase and phospholamban mRNA expression in response to pressure overload and thyroid hormone.
The sarcoplasmic reticulum (SR) and the contractile protein myosin play an important role in myocardial performance. Both of these systems exhibit plasticity--i.e., quantitative and/or qualitative reorganization during development and in response to stress. Recent studies indicate that SR Ca2+ uptake function is altered in adaptive cardiac hypertrophy and failure. The molecular basis (genetic and phenotypic) for these changes is not understood. In an effort to determine the underlying causes of these changes, we characterized the rabbit cardiac Ca2+-ATPase phenotype by molecular cloning and ribonuclease A mapping analysis. Our results show that the heart muscle expresses only the slow-twitch SR Ca2+-ATPase isoform. Second, we quantitated the steady-state mRNA levels of two major SR Ca2+ regulatory proteins, the Ca2+-ATPase and phospholamban, to see whether changes in mRNA content might provide insight into the basis for functional modification in the SR of hypertrophied hearts. In response to pressure overload hypertrophy, the relative level of the slow-twitch/cardiac SR Ca2+-ATPase mRNA was decreased to 34% of control at 1 week. The relative Ca2+-ATPase mRNA level increased to 167% of control after 3 days of treatment with thyroid hormone. In contrast, in hypothyroid animals, the relative Ca2+-ATPase mRNA level decreased to 51% of control at 2 weeks. The relative level of phospholamban mRNA was decreased to 36% in 1-week pressure overload. Hyperthyroidism induced a decrease to 61% in the phospholamban mRNA level after 3 days of treatment, while hypothyroidism had virtually no effect on phospholamban mRNA levels. These data indicate that the expression of SR Ca2+-ATPase and phospholamban mRNA may not be coordinately regulated during myocardial adaptation to different physiological conditions.
Nagai
R
R
Department of Physiology and Biophysics, University of Vermont College of Medicine, Burlington 05405.
Zarain-Herzberg
A
A
Brandl
C J
CJ
Fujii
J
J
Tada
M
M
MacLennan
D H
DH
Alpert
N R
NR
Periasamy
M
M
D000818:Animals; D001794:Blood Pressure; D002135:Calcium-Binding Proteins / Q000235:genetics*; D000252:Calcium-Transporting ATPases / Q000235:genetics*; D006332:Cardiomegaly / Q000235:genetics*; D005786:Gene Expression Regulation; D006321:Heart / Q000502:physiology*; D007037:Hypothyroidism / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D013974:Thyroxine / Q000494:pharmacology*; D000099211:Phospholamban
D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D012333:RNA, Messenger; D013974:Thyroxine; D000099211:Phospholamban