title: 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: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors: Jakob
authors: J
authors: Voelkl
authors: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors: Ioana
authors: I
authors: Alesutan
authors: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors: Tatsiana
authors: T
authors: Pakladok
authors: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors: Robert
authors: R
authors: Viereck
authors: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors: Martina
authors: M
authors: Feger
authors: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors: Sobuj
authors: S
authors: Mia
authors: Department of Cardiology and Cardiovascular Medicine, University of Tübingen, Tübingen, Germany.
authors: Tanja
authors: T
authors: Schönberger
authors: Center for Biochemistry, Institute of Biochemistry I, University of Cologne, Köln, Germany.
authors: Angelika A
authors: AA
authors: Noegel
authors: Department of Cardiology and Cardiovascular Medicine, University of Tübingen, Tübingen, Germany.
authors: Meinrad
authors: M
authors: Gawaz
authors: Department of Physiology, University of Tübingen, Tübingen, Germany. Electronic address: florian.lang@uni-tuebingen.de.
authors: Florian
authors: F
authors: Lang
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D017310:Annexin A7 / Q000235:genetics / Q000378:metabolism*; D001011:Aorta / Q000473:pathology; D015153:Blotting, Western; D002135:Calcium-Binding Proteins; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003251:Constriction, Pathologic; D015870:Gene Expression / Q000187:drug effects; D006984:Hypertrophy; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism*; D034622:RNA Interference; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D000099242:Atrial Natriuretic Factor Receptor B
chemical_list: D000318:Adrenergic beta-Agonists; D017310:Annexin A7; D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007545:Isoproterenol; D009124:Muscle Proteins; D050778:NFATC Transcription Factors; D017461:Receptors, Atrial Natriuretic Factor; D000099242:Atrial Natriuretic Factor Receptor B; C511512:DSCR1 protein, mouse
keywords: Annexin A7; HL-1 cardiomyocytes; NFAT; Pressure overload