Annexin A7 deficiency potentiates cardiac NFAT activity promoting hypertrophic signaling.

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.

• Authors: Jakob Voelkl, Ioana Alesutan, Tatsiana Pakladok, Robert Viereck, Martina Feger, Sobuj Mia, Tanja Schönberger, Angelika A Noegel, Meinrad Gawaz, Florian Lang
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 445 Issue 1 Pg. 244-9 (Feb 28 2014) ISSN: 1090-2104 [Electronic] United States
• PMID: 24508799 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Adrenergic beta-Agonists
• Annexin A7
• Calcium-Binding Proteins
• DSCR1 protein, mouse
• Intracellular Signaling Peptides and Proteins
• Muscle Proteins
• NFATC Transcription Factors
• Receptors, Atrial Natriuretic Factor
• atrial natriuretic factor receptor B
• Isoproterenol

Topics

• Adrenergic beta-Agonists (pharmacology)
• Animals
• Annexin A7 (genetics, metabolism)
• Aorta (pathology)
• Blotting, Western
• Calcium-Binding Proteins
• Cell Line
• Cell Nucleus (metabolism)
• Constriction, Pathologic
• Gene Expression (drug effects)
• Hypertrophy
• Intracellular Signaling Peptides and Proteins (genetics, metabolism)
• Isoproterenol (pharmacology)
• Male
• Mice
• Mice, 129 Strain
• Mice, Knockout
• Microscopy, Confocal
• Muscle Proteins (genetics, metabolism)
• Myocardium (metabolism, pathology)
• Myocytes, Cardiac (cytology, drug effects, metabolism)
• NFATC Transcription Factors (metabolism)
• RNA Interference
• Receptors, Atrial Natriuretic Factor (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction