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

First Author  Suzuki YJ Year  1999
Journal  Cell Calcium Volume  25
Issue  6 Pages  401-7
PubMed ID  10579051 Mgi Jnum  J:59873
Mgi Id  MGI:1352243 Doi  10.1054/ceca.1999.0037
Citation  Suzuki YJ, et al. (1999) Regulation of GATA-4 and AP-1 in transgenic mice overexpressing cardiac calsequestrin. Cell Calcium 25(6):401-7
abstractText  Transgenic mouse hearts overexpressing the Ca(2+)-binding protein calsequestrin (CSQ) have an accompanying 10-fold increase in the sarcoplasmic reticulum (SR) Ca2+ load, however, exhibits slow and small Ca(2+)-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 type1a 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.
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