TY - JOUR
T1 - Prostaglandin E2 induces hypertrophic changes and suppresses α-skeletal actin gene expression in rat cardiomyocytes
AU - Miyatake, Satoru
AU - Manabe-Kawaguchi, Haruko
AU - Watanabe, Kikuko
AU - Hori, Shingo
AU - Aikawa, Naoki
AU - Fukuda, Keiichi
PY - 2007/11
Y1 - 2007/11
N2 - 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 [H]-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 α-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 α-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 α-skeletal actin gene expression in part via EP4.
AB - 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 [H]-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 α-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 α-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 α-skeletal actin gene expression in part via EP4.
KW - Cardiac hypertrophy
KW - Prostaglandin E
KW - α-skeletal actin
UR - http://www.scopus.com/inward/record.url?scp=36348999736&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=36348999736&partnerID=8YFLogxK
U2 - 10.1097/FJC.0b013e318145ae2e
DO - 10.1097/FJC.0b013e318145ae2e
M3 - Article
C2 - 18030065
AN - SCOPUS:36348999736
VL - 50
SP - 548
EP - 554
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
SN - 0160-2446
IS - 5
ER -