The expression of SR calcium transport ATPase and the Na(+)/Ca(2+)Exchanger are antithetically regulated during mouse cardiac development and in Hypo/hyperthyroidism.
The mouse has been used extensively for generating transgenic animal models to study cardiovascular disease. Recently, a number of transgenic mouse models have been created to investigate the importance of sarcoplasmic reticulum (SR) Ca(2+)transport proteins in cardiac pathophysiology. However, the expression and regulation of cardiac SR Ca(2+)ATPase and other Ca(2+)transport proteins have not been studied in detail in the mouse. In this study, we used multiplex RNase mapping analysis to determine SERCA2, phospholamban (PLB), and Na(+)/Ca(2+)-exchanger (NCX-1) gene expression throughout mouse heart development and in hypo/hyperthyroid animals. Our results demonstrate that the expression of SERCA2 and PLB mRNA increase eight-fold from fetal to adult stages, indicating that SR function increases with heart development. In contrast, the expression of the Na(+)/Ca(2+)-exchanger gene is two-fold higher in fetal heart compared to adult. Our study also makes the important observation that in hypothyroidic hearts the NCX-1 mRNA and protein levels were upregulated, whereas the SERCA2 mRNA/protein levels were downregulated. In hyperthyroidic hearts, however, an opposite response was identified. These findings are important and point out that the expression of NCX-1 is regulated antithetically to that of SERCA2 during heart development and in response to alterations in thyroid hormone levels.
Reed
T D
TD
Laboratory of Molecular Cardiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0524, USA.
Babu
G J
GJ
Ji
Y
Y
Zilberman
A
A
Ver Heyen
M
M
Wuytack
F
F
Periasamy
M
M
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology / Q000254:growth & development*; D006980:Hyperthyroidism / Q000378:metabolism*; D007037:Hypothyroidism / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000235:genetics*; D013963:Thyroid Hormones / Q000378:metabolism
D007527:Isoenzymes; D019831:Sodium-Calcium Exchanger; D013963:Thyroid Hormones; D000252:Calcium-Transporting ATPases