Regulation of GATA-4 and AP-1 in transgenic mice overexpressing cardiac calsequestrin

Y. J. Suzuki, T. Ikeda, S. S. Shi, K. Kitta, Y. M. Kobayashi, M. Morad, L. R. Jones, J. B. Blumberg

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Transgenic mouse hearts overexpressing the Ca2+-binding protein calsequestrin (CSQ) have an accompanying 10-fold increase in the sarcoplasmic reticulum (SR) Ca2+ load, however, exhibits slow and small Ca2+-induced Ca2+ release. Such slow kinetics of Ca2+ release may have activated excitation-transcription coupling as CSQ overexpressing hearts have induced levels of NFAT and GATA-4 activities and higher levels of c-fos mRNA and cFos protein compared to those of non-transgenic littermates. Adaptive responses, however, appear to downregulate transcriptional regulators controlling c-fos gene including serum response factor and Ca2+/cAMP response element-binding protein. CSQ-overexpressing hearts also had decreased levels of cJun protein, resulting in downregulated AP-1 activity. The mRNA levels of angiotensin II type(1a) receptor which requires AP-1 and GATA-4 for gene transcription was suppressed in CSQ overexpressing hearts. These results demonstrate that CSQ can regulate GATA-4- and AP-1-dependent transcriptional events, indicating the existence of SR-nuclear circuits of signal transduction in adult cardiac muscle.

Original languageEnglish (US)
Pages (from-to)401-407
Number of pages7
JournalCell Calcium
Volume25
Issue number6
DOIs
StatePublished - Jun 1999

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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