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Transgenic overexpression of the Ca2+-binding protein S100A1 in the heart leads to increased in vivo myocardial contractile performance.

Publication ,  Journal Article
Most, P; Remppis, A; Pleger, ST; Löffler, E; Ehlermann, P; Bernotat, J; Kleuss, C; Heierhorst, J; Ruiz, P; Witt, H; Karczewski, P; Mao, L ...
Published in: J Biol Chem
September 5, 2003

S100A1, a Ca2+-sensing protein of the EF-hand family, is most highly expressed in myocardial tissue, and cardiac S100A1 overexpression in vitro has been shown to enhance myocyte contractile properties. To study the physiological consequences of S100A1 in vivo, transgenic mice were developed with cardiac-restricted overexpression of S100A1. Characterization of two independent transgenic mouse lines with approximately 4-fold overexpression of S100A1 in the myocardium revealed a marked augmentation of in vivo basal cardiac function that remained elevated after beta-adrenergic receptor stimulation. Contractile function and Ca2+ handling properties were increased in ventricular cardiomyocytes isolated from S100A1 transgenic mice. Enhanced cellular Ca2+ cycling by S100A1 was associated both with increased sarcoplasmic reticulum Ca2+ content and enhanced sarcoplasmic reticulum Ca2+-induced Ca2+ release, and S100A1 was shown to associate with the cardiac ryanodine receptor. No alterations in beta-adrenergic signal transduction or major cardiac Ca2+-cycling proteins occurred, and there were no signs of hypertrophy with chronic cardiac S100A1 overexpression. Our findings suggest that S100A1 plays an important in vivo role in the regulation of cardiac function perhaps through interacting with the ryanodine receptor. Because S100A1 protein expression is down-regulated in heart failure, increasing S100A1 expression in the heart may represent a novel means to augment contractility.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

September 5, 2003

Volume

278

Issue

36

Start / End Page

33809 / 33817

Location

United States

Related Subject Headings

  • Time Factors
  • Signal Transduction
  • Sarcoplasmic Reticulum
  • S100 Proteins
  • Ryanodine Receptor Calcium Release Channel
  • Receptors, Adrenergic, beta
  • Protein Binding
  • Precipitin Tests
  • Myocardium
  • Myocardial Contraction
 

Citation

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Most, P., Remppis, A., Pleger, S. T., Löffler, E., Ehlermann, P., Bernotat, J., … Koch, W. J. (2003). Transgenic overexpression of the Ca2+-binding protein S100A1 in the heart leads to increased in vivo myocardial contractile performance. J Biol Chem, 278(36), 33809–33817. https://doi.org/10.1074/jbc.M301788200
Most, Patrick, Andrew Remppis, Sven T. Pleger, Eva Löffler, Philipp Ehlermann, Juliane Bernotat, Christiane Kleuss, et al. “Transgenic overexpression of the Ca2+-binding protein S100A1 in the heart leads to increased in vivo myocardial contractile performance.J Biol Chem 278, no. 36 (September 5, 2003): 33809–17. https://doi.org/10.1074/jbc.M301788200.
Most P, Remppis A, Pleger ST, Löffler E, Ehlermann P, Bernotat J, et al. Transgenic overexpression of the Ca2+-binding protein S100A1 in the heart leads to increased in vivo myocardial contractile performance. J Biol Chem. 2003 Sep 5;278(36):33809–17.
Most, Patrick, et al. “Transgenic overexpression of the Ca2+-binding protein S100A1 in the heart leads to increased in vivo myocardial contractile performance.J Biol Chem, vol. 278, no. 36, Sept. 2003, pp. 33809–17. Pubmed, doi:10.1074/jbc.M301788200.
Most P, Remppis A, Pleger ST, Löffler E, Ehlermann P, Bernotat J, Kleuss C, Heierhorst J, Ruiz P, Witt H, Karczewski P, Mao L, Rockman HA, Duncan SJ, Katus HA, Koch WJ. Transgenic overexpression of the Ca2+-binding protein S100A1 in the heart leads to increased in vivo myocardial contractile performance. J Biol Chem. 2003 Sep 5;278(36):33809–33817.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

September 5, 2003

Volume

278

Issue

36

Start / End Page

33809 / 33817

Location

United States

Related Subject Headings

  • Time Factors
  • Signal Transduction
  • Sarcoplasmic Reticulum
  • S100 Proteins
  • Ryanodine Receptor Calcium Release Channel
  • Receptors, Adrenergic, beta
  • Protein Binding
  • Precipitin Tests
  • Myocardium
  • Myocardial Contraction