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, Larry Jones, J. B. Blumberg

Research output: Contribution to journalArticle

13 Citations (Scopus)

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

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Calsequestrin
Transcription Factor AP-1
Transgenic Mice
Sarcoplasmic Reticulum
Down-Regulation
Serum Response Factor
fos Genes
Cyclic AMP Response Element-Binding Protein
Messenger RNA
Angiotensin Type 1 Receptor
Signal Transduction
Myocardium
Carrier Proteins
Proteins
Genes

ASJC Scopus subject areas

  • Cell Biology
  • Endocrinology

Cite this

Suzuki, Y. J., Ikeda, T., Shi, S. S., Kitta, K., Kobayashi, Y. M., Morad, M., ... Blumberg, J. B. (1999). Regulation of GATA-4 and AP-1 in transgenic mice overexpressing cardiac calsequestrin. Cell Calcium, 25(6), 401-407. https://doi.org/10.1054/ceca.1999.0037

Regulation of GATA-4 and AP-1 in transgenic mice overexpressing cardiac calsequestrin. / Suzuki, Y. J.; Ikeda, T.; Shi, S. S.; Kitta, K.; Kobayashi, Y. M.; Morad, M.; Jones, Larry; Blumberg, J. B.

In: Cell Calcium, Vol. 25, No. 6, 06.1999, p. 401-407.

Research output: Contribution to journalArticle

Suzuki, YJ, Ikeda, T, Shi, SS, Kitta, K, Kobayashi, YM, Morad, M, Jones, L & Blumberg, JB 1999, 'Regulation of GATA-4 and AP-1 in transgenic mice overexpressing cardiac calsequestrin', Cell Calcium, vol. 25, no. 6, pp. 401-407. https://doi.org/10.1054/ceca.1999.0037
Suzuki YJ, Ikeda T, Shi SS, Kitta K, Kobayashi YM, Morad M et al. Regulation of GATA-4 and AP-1 in transgenic mice overexpressing cardiac calsequestrin. Cell Calcium. 1999 Jun;25(6):401-407. https://doi.org/10.1054/ceca.1999.0037
Suzuki, Y. J. ; Ikeda, T. ; Shi, S. S. ; Kitta, K. ; Kobayashi, Y. M. ; Morad, M. ; Jones, Larry ; Blumberg, J. B. / Regulation of GATA-4 and AP-1 in transgenic mice overexpressing cardiac calsequestrin. In: Cell Calcium. 1999 ; Vol. 25, No. 6. pp. 401-407.
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