Activators of PPARgamma antagonize protection of cardiac myocytes by endothelin-1

Natsuhiko Ehara; Koji Hasegawa; Koh Ono; Teruhisa Kawamura; Eri Iwai-Kanai; Tatsuya Morimoto; Masaharu Akao; Souichi Adachi; Toru Kita

doi:10.1016/j.bbrc.2004.06.147

Activators of PPARgamma antagonize protection of cardiac myocytes by endothelin-1

Biochem Biophys Res Commun. 2004 Aug 20;321(2):345-9. doi: 10.1016/j.bbrc.2004.06.147.

Authors

Natsuhiko Ehara¹, Koji Hasegawa, Koh Ono, Teruhisa Kawamura, Eri Iwai-Kanai, Tatsuya Morimoto, Masaharu Akao, Souichi Adachi, Toru Kita

Affiliation

¹ Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, 54 Kawara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.

PMID: 15358182
DOI: 10.1016/j.bbrc.2004.06.147

Abstract

Endothelin-1 (ET-1) is a potent survival factor against myocardial cell apoptosis. This anti-apoptotic effect of ET-1 is mediated in part through calcineurin/NFATc-dependent induction of bcl-2 expression. Since it has been reported that peroxisome proliferator-activated receptor-gamma (PPARgamma) interacts with NFATc, we investigated the effects of PPARgamma ligands on anti-apoptotic effects of ET-1 in cardiac myocytes. In primary cardiac myocytes from neonatal rats, administration of PPARgamma activators (15-deoxy-delta12,14-prostaglandin J2 and troglitazone) attenuated the anti-apoptotic effects of ET-1. These activators abolished the ET-1-stimulated increase in bcl-2 expression and in binding of cardiac NFATc to the bcl-2 NFAT site. These findings demonstrate that activators of PPARgamma perturb the anti-apoptotic effects of ET-1 in cardiac myocytes and that this perturbation is, in part, based on functional transcriptional cross-talk between NFATc and PPARgamma.

MeSH terms

Animals
Apoptosis
Cardiotonic Agents / antagonists & inhibitors*
Cardiotonic Agents / pharmacology
Cells, Cultured
Chromans / pharmacology
DNA / genetics
DNA / metabolism
DNA-Binding Proteins / metabolism
Endothelin-1 / antagonists & inhibitors*
Endothelin-1 / pharmacology*
Myocytes, Cardiac / cytology
Myocytes, Cardiac / drug effects*
Myocytes, Cardiac / metabolism*
NFATC Transcription Factors
Nuclear Proteins*
Prostaglandin D2 / analogs & derivatives
Prostaglandin D2 / pharmacology
Protein Binding / drug effects
Proto-Oncogene Proteins c-bcl-2 / metabolism
Rats
Receptors, Cytoplasmic and Nuclear / agonists*
Receptors, Cytoplasmic and Nuclear / genetics
Receptors, Cytoplasmic and Nuclear / metabolism*
Thiazolidinediones / pharmacology
Transcription Factors / agonists*
Transcription Factors / genetics
Transcription Factors / metabolism*
Troglitazone

Substances

15-deoxy-delta(12,14)-prostaglandin J2
Cardiotonic Agents
Chromans
DNA-Binding Proteins
Endothelin-1
NFATC Transcription Factors
Nuclear Proteins
Proto-Oncogene Proteins c-bcl-2
Receptors, Cytoplasmic and Nuclear
Thiazolidinediones
Transcription Factors
DNA
Troglitazone
Prostaglandin D2