Activation of peroxisome proliferator-activated receptor gamma inhibits endothelin-1-induced cardiac hypertrophy via the calcineurin/NFAT signaling pathway.
Peroxisome proliferator-activated receptor gamma (PPAR-gamma) has been described as a negative regulator of cardiac hypertrophy. A better understanding of PPAR-gamma and cardiac hypertrophy may facilitate the development of novel therapeutic strategies to treat heart diseases related to cardiac hypertrophy by mimicking the naturally preferred mechanisms. In the present study, we investigated the interaction between PPAR-gamma and calcineurin/nuclear factor of activated T-cells (NFAT) in endothelin-1 (ET-1)-induced hypertrophy of neonatal rat cardiac myocytes. The results suggest that the treatment of cultured cardiac myocytes with a PPAR-gamma ligand, rosiglitazone, inhibited the ET-1-induced increase in protein synthesis, surface area, calcineurin enzymatic activity, and protein expression. Both the application of rosiglitazone and overexpression of the PPAR-gamma inhibited the nuclear translocation of NFATc4. Moreover, co-immunoprecipitation studies showed that rosiglitazone enhanced the association between PPAR-gamma and calcineurin/NFAT. These results suggest that ET-1-induced cardiac hypertrophy is inhibited by activation of PPAR-gamma, which is at least partly due to cross-talk between PPAR-gamma and calcineurin/NFAT.
Bao
Yingxia
Y
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, 74 Zhongshan II Road, Guangzhou, 510080, People's Republic of China.
Li
Ruifang
R
Jiang
Jianmin
J
Cai
Birong
B
Gao
Jie
J
Le
Kang
K
Zhang
Fangyan
F
Chen
Shaorui
S
Liu
Peiqing
P
D000818:Animals; D000831:Animals, Newborn; D019703:Calcineurin / Q000378:metabolism*; D006332:Cardiomegaly / Q000201:enzymology* / Q000473:pathology; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D019332:Endothelin-1 / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D050778:NFATC Transcription Factors / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects; D013499:Surface Properties; D045162:Thiazolidinediones / Q000494:pharmacology
D019332:Endothelin-1; D050778:NFATC Transcription Factors; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D016572:Cyclosporine; D019703:Calcineurin