title: Altered calcium regulation in isolated cardiomyocytes from Egr-1 knock-out mice.
abstract: Early growth response-1 one gene (Egr-1), one of the immediate early response genes, plays an important role in the adaptive response of the myocardium to hypertrophic stimuli. We aimed to investigate the effects of Egr-1 deletion on cardiac function. Egr-1 knock-out (Egr-1(-/-)) homozygous mice were employed to evaluate the electrophysiological and molecular properties of left ventricular cardiomyocytes (VCM) by using patch-clamp technique, intracellular calcium measurements, real-time PCR, and Western blot. Action potential was prolonged and diastolic potential was positive-shifted in VCMs isolated from Egr-1(-/-) mice, in comparison with those from their wild-type (WT) littermates. The calcium content of the sarcoplasmic reticulum was reduced and the decay time for steady-state calcium transient slowed down. Serca2, Ryr, L-type Ca(2+)-channel, and PLB mRNA expression were reduced in Egr-1(-/-) mice compared with the controls. Moreover, Serca2 protein was reduced, while the amount of Ncx1 protein was increased in Egr-1(-/-) hearts compared with those of the WT littermates. Furthermore, genes involved in heart development (GATA-4, TGF-β) and in Egr-1 regulation (Nab1, Nab2) were down regulated in Egr-1(-/-) mice. These results suggest that Egr-1 plays a pivotal role in regulating excitation-contraction coupling in cardiac myocytes.
authors.affiliation: a Department of Medico-surgical Sciences and Biotechnologies, "Sapienza" University of Rome, Corso della Repubblica 79, Latina, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Pacini
authors.forename: Silvia
authors.initials: S
authors.lastname: Suffredini
authors.forename: Donatella
authors.initials: D
authors.lastname: Ponti
authors.forename: Raffaele
authors.initials: R
authors.lastname: Coppini
authors.forename: Giacomo
authors.initials: G
authors.lastname: Frati
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ragona
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cerbai
authors.forename: Antonella
authors.initials: A
authors.lastname: Calogero
mesh_terms: D000200:Action Potentials / Q000235:genetics; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D051766:Early Growth Response Protein 1 / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D050991:GATA4 Transcription Factor; C499849:NCX1 protein, mouse; C490624:Nab1 protein, mouse; C099945:Nab2 protein, mouse; D009363:Neoplasm Proteins; D012097:Repressor Proteins; D019831:Sodium-Calcium Exchanger; D016212:Transforming Growth Factor beta; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506947:Atp2a2 protein, mouse; D002118:Calcium