The expression of SR calcium transport ATPase and the Na(+)/Ca(2+)Exchanger are antithetically regulated during mouse cardiac development and in Hypo/hyperthyroidism

J Mol Cell Cardiol. 2000 Mar;32(3):453-64. doi: 10.1006/jmcc.1999.1095.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium-Transporting ATPases / genetics*
  • Gene Expression Regulation, Developmental*
  • Heart / embryology
  • Heart / growth & development*
  • Hyperthyroidism / metabolism*
  • Hypothyroidism / metabolism*
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Mice
  • Muscle Fibers, Fast-Twitch / metabolism
  • Sarcoplasmic Reticulum / metabolism*
  • Sodium-Calcium Exchanger / genetics*
  • Thyroid Hormones / metabolism

Substances

  • Isoenzymes
  • Sodium-Calcium Exchanger
  • Thyroid Hormones
  • Calcium-Transporting ATPases