title: Prostaglandin E2 induces hypertrophic changes and suppresses alpha-skeletal actin gene expression in rat cardiomyocytes.
abstract: Prostaglandin E2 (PGE2) is a potent lipid mediator in a diverse range of biological processes. This study examined the hypertrophic effect of PGE2 in primary cultured rat neonatal cardiomyocytes. PGE2 increased total protein synthesis in a dose-dependent manner, as measured by [3H]-phenylalanine uptake. PGE2 increased the cell size and surface area and induced the reorganization of myofilaments. Phosphorylation of the p42/44 and p38 mitogen-activated protein kinases (MAPK) was also induced by PGE2, and U0126 [a mitogen-activated extracellular signal regulated kinase kinase (MEK) 1/2 inhibitor] significantly inhibited the PGE2-induced protein synthesis. Expression of the hypertrophic marker genes, atrial natriuretic peptide and brain natriuretic peptide, was increased by PGE2, but expression of the alpha-skeletal actin gene was significantly attenuated. Transcripts for all 4 PGE2 receptor subtypes (EP1, EP2, EP3, and EP4) were detected in the cardiomyocytes. AE3-208 (an EP4-selective antagonist) significantly inhibited the alpha-skeletal actin gene suppression induced by PGE2, whereas SC51322 (an EP1-selective antagonist) did not. In conclusion, PGE2 induced hypertrophic changes in cardiomyocytes and attenuated alpha-skeletal actin gene expression in part via EP4.
authors.affiliation: Department of Regenerative Medicine and Advanced Cardiac Therapeutics, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Miyatake
authors.forename: Haruko
authors.initials: H
authors.lastname: Manabe-Kawaguchi
authors.forename: Kikuko
authors.initials: K
authors.lastname: Watanabe
authors.forename: Shingo
authors.initials: S
authors.lastname: Hori
authors.forename: Naoki
authors.initials: N
authors.lastname: Aikawa
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D000199:Actins / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000235:genetics; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D049108:Cell Enlargement / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D009570:Nitriles / Q000494:pharmacology; D010654:Phenylbutyrates / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors / Q000235:genetics; D058309:Receptors, Prostaglandin E, EP4 Subtype; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C487890:4-(4-cyano-2-(2-(4-fluoronaphthalen-1-yl)propionylamino)phenyl)butyric acid; D000199:Actins; D002070:Butadienes; D007093:Imidazoles; D009281:Naphthalenes; D009570:Nitriles; D010654:Phenylbutyrates; D011448:Prostaglandin Antagonists; D047428:Protein Kinase Inhibitors; C545652:Ptger4 protein, rat; D011725:Pyridines; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; C113580:U 0126; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D015232:Dinoprostone; C093642:SB 203580