Ca2+-induced PARP-1 activation and ANF expression are coupled events in cardiomyocytes
Abstract
The nuclear protein PARP-1 [poly(ADP-ribose) polymerase-1] is activated in cardiomyocytes exposed to hypoxia causing DNA breaks. Unlike this stress-induced PARP-1 activation, our results provide evidence for Ca2+-induced PARP-1 activation in contracting newborn cardiomyocytes treated with growth factors and hormones that increased their contraction rate, induced intracellular Ca2+ mobilization and its rhythmical and transient translocation into the nucleus. Furthermore, activated PARP-1 up-regulated the activity of phosphorylated ERK (extracellular-signal-regulated kinase) in the nucleus, promoting expression of the Elk1 target gene c-fos. Up-regulation of the transcription factor c-Fos/GATA-4 promoted ANF (atrial natriuretic factor) expression. Given that expression of ANF is known to be implicated in morphological changes, growth and development of cardiomyocytes, these results outline a PARP-1-dependent signal transduction mechanism that links contraction rate and Ca2+ mobilization with the expression of genes underlying morphological changes in cardiomyocytes.
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References 55 · Cited by 23
- Authors
- Geistrikh, I., Visochek, L., Klein, R., Miller, L., Mittelman, L., Shainberg, A., & Cohen-Armon, M.
- Affiliations
- Bar-Ilan University (IL)
- Tel Aviv University (IL)
- Neufeld Cardiac Research Institute, Sackler Faculty of Medicine, Tel-Aviv University, 69978 Tel-Aviv, Israel
- Corresponding author
- Geistrikh, Ilona
- Visochek, Leonid
- Klein, Rodika
- Miller, Liron
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2011-08-12
- Volume
- 438
- Issue
- 2
- Pages
- 337-347
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- OpenAlex
- W2334842588
- Cited by
- 23
- References
- 55
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 1 · 2012: 2
- FWCI
- 0.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical Journal (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Keywords
- PARP1, calcium signaling, cardiomyocytes, atrial natriuretic peptide, c-fos, GATA4, ERK1/2 phosphorylation, Elk-1, nuclear translocation, cardiomyocyte contraction, growth factors, signal transduction, gene expression regulation
- MeSH terms
- Poly (ADP-Ribose) Polymerase-1, Angiotensin II, Animals, Animals, Newborn, Calcium, Enzyme Activation, Gene Expression Regulation, Myocardial Contraction, Atrial Natriuretic Factor, Phosphorylation, Poly(ADP-ribose) Polymerases, Promoter Regions, Genetic, Protein Binding, Ribose, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Myocytes, Cardiac, Intracellular Space, Extracellular Signal-Regulated MAP Kinases, GATA4 Transcription Factor, Rats
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