title: 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 Ca(2+)-induced PARP-1 activation in contracting newborn cardiomyocytes treated with growth factors and hormones that increased their contraction rate, induced intracellular Ca(2+) 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 Ca(2+) mobilization with the expression of genes underlying morphological changes in cardiomyocytes.
authors.affiliation: Neufeld Cardiac Research Institute, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
authors.forename: Ilona
authors.initials: I
authors.lastname: Geistrikh
authors.forename: Leonid
authors.initials: L
authors.lastname: Visochek
authors.forename: Rodika
authors.initials: R
authors.lastname: Klein
authors.forename: Liron
authors.initials: L
authors.lastname: Miller
authors.forename: Leonid
authors.initials: L
authors.lastname: Mittelman
authors.forename: Asher
authors.initials: A
authors.lastname: Shainberg
authors.forename: Malka
authors.initials: M
authors.lastname: Cohen-Armon
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D050991:GATA4 Transcription Factor / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology*; D010766:Phosphorylation / Q000187:drug effects; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012266:Ribose / Q000378:metabolism
chemical_list: D050991:GATA4 Transcription Factor; C084365:Gata4 protein, rat; D016760:Proto-Oncogene Proteins c-fos; D000804:Angiotensin II; D012266:Ribose; D009320:Atrial Natriuretic Factor; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium