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Biochem Biophys Res Commun. 2014 Feb 28;445(1):244-9. doi: 10.1016/j.bbrc.2014.01.186. Epub 2014 Feb 6.

Annexin A7 deficiency potentiates cardiac NFAT activity promoting hypertrophic signaling.

Author information

1
Department of Physiology, University of Tübingen, Tübingen, Germany.
2
Department of Cardiology and Cardiovascular Medicine, University of Tübingen, Tübingen, Germany.
3
Center for Biochemistry, Institute of Biochemistry I, University of Cologne, Köln, Germany.
4
Department of Physiology, University of Tübingen, Tübingen, Germany. Electronic address: florian.lang@uni-tuebingen.de.

Abstract

Annexin A7 (Anxa7) is a cytoskeletal protein interacting with Ca(2+) signaling which in turn is a crucial factor for cardiac remodeling following cardiac injury. The present study explored whether Anxa7 participates in the regulation of cardiac stress signaling. To this end, mice lacking functional Anxa7 (anxa7(-/-)) and wild-type mice (anxa7(+/+)) were investigated following pressure overload by transverse aortic constriction (TAC). In addition, HL-1 cardiomyocytes were silenced with Anxa7 siRNA and treated with isoproterenol. Transcript levels were determined by quantitative RT-PCR, transcriptional activity by luciferase reporter assay and protein abundance by Western blotting and confocal microscopy. As a result, TAC treatment increased the mRNA and protein levels of Anxa7 in wild-type mice. Moreover, TAC increased heart weight to body weight ratio and the cardiac mRNA levels of αSka, Nppb, Col1a1, Col3a1 and Rcan1, effects more pronounced in anxa7(-/-) mice than in anxa7(+/+) mice. Silencing of Anxa7 in HL-1 cardiomyocytes significantly increased nuclear localization of Nfatc1. Furthermore, Anxa7 silencing increased NFAT-dependent transcriptional activity as well as αSka, Nppb, and Rcan1 mRNA levels both, under control conditions and following β-adrenergic stimulation by isoproterenol. These observations point to an important role of annexin A7 in the regulation of cardiac NFAT activity and hypertrophic response following cardiac stress conditions.

KEYWORDS:

Annexin A7; HL-1 cardiomyocytes; NFAT; Pressure overload

PMID:
24508799
DOI:
10.1016/j.bbrc.2014.01.186
[Indexed for MEDLINE]
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