Regulation of Ncx1 gene expression in the normal and hypertrophic heart

Donald R. Menick, Ludivine Renaud, Avery Buchholz, Joachim G. Müller, Hongming Zhou, Christiana S. Kappler, Steven W. Kubalak, Simon J. Conway, Lin Xu

Research output: Chapter in Book/Report/Conference proceedingConference contribution

24 Scopus citations

Abstract

The Na+/Ca2+ exchanger (NCX1) is crucial in the regulation of [Ca2+]i in the cardiac myocyte. The exchanger is upregulated in cardiac hypertrophy, ischemia, and failure. This upregulation can have an effect on Ca2+ transients and possibly contribute to diastolic dysfunction and an increased risk of arrhythmias. Studies from both in vivo and in vitro model systems have provided an initial skeleton of the potential signaling pathways that regulate the exchanger during development, growth, and hypertrophy. The Ncx1 gene is upregulated in response to α-adrenergic stimulation. We have shown that this is via p38α activation of transcription factors binding to the Ncx1 promotor at the -80 CArG element. Interestingly, most of the elements, including the CArG element, which we have demonstrated to be important for regulation of Ncx1 expression are in the proximal 184 bp of the promotor. Using a transgenic mouse, we have shown that the proximal 184 bp is sufficient for expression of reporter genes in adult cardiomyocytes and for the correct spatiotemporal pattern of Ncx1 expression in development but not for upregulation in response to pressure overload.

Original languageEnglish (US)
Title of host publicationSodium-Calcium Exchange and the Plasma Membrane Ca2+ATPase in Ce;; Funcyion
Subtitle of host publicationFifth International Conference
PublisherBlackwell Publishing Inc.
Pages195-203
Number of pages9
ISBN (Print)1573316490, 9781573316491
DOIs
StatePublished - Mar 2007

Publication series

NameAnnals of the New York Academy of Sciences
Volume1099
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Cardiac hypertrophy
  • Na/Ca exchanger
  • NCX1
  • Regulation of gene expression
  • Signal transduction
  • Transgenic mice

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Menick, D. R., Renaud, L., Buchholz, A., Müller, J. G., Zhou, H., Kappler, C. S., Kubalak, S. W., Conway, S. J., & Xu, L. (2007). Regulation of Ncx1 gene expression in the normal and hypertrophic heart. In Sodium-Calcium Exchange and the Plasma Membrane Ca2+ATPase in Ce;; Funcyion: Fifth International Conference (pp. 195-203). (Annals of the New York Academy of Sciences; Vol. 1099). Blackwell Publishing Inc.. https://doi.org/10.1196/annals.1387.058