Inhibitory effects of rosiglitazone against endothelin-1-induced proliferation of rat cardiac myocytes: the role of PKC-c-fos pathway.
- Author:
Xiao-Xing ZHU
1
;
Xiao-Lin NIU
;
Ding-Zhang CHEN
;
Xiao-Dong ZHOU
;
Jian-Ming PEI
;
Miao-Zhang ZHU
;
Jun GUO
;
Xiao-Ling ZHU
;
Wen-Qing WANG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Animals, Newborn; Blotting, Western; Cell Enlargement; drug effects; Cells, Cultured; Dose-Response Relationship, Drug; Endothelin-1; pharmacology; Hypoglycemic Agents; pharmacology; Myocytes, Cardiac; cytology; drug effects; metabolism; Protein Kinase C; metabolism; Proto-Oncogene Proteins c-fos; biosynthesis; Rats; Rats, Sprague-Dawley; Signal Transduction; drug effects; Tetradecanoylphorbol Acetate; pharmacology; Thiazolidinediones; pharmacology
- From: Journal of Southern Medical University 2008;28(6):1056-1060
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the mechanism of rosiglitazone (RSG, the activator of peroxisome proliferators activated receptor lambda) for inhibiting endothelin-1 (ET-1)-induced neonatal rat cardiac myocyte hypertrophy and the role of protein kinase C (PKC) and c-fos.
METHODSIn vitro cultured neonatal rat cardiac myocytes were treated with ET-1, phorbol ester (PMA, the PKC activator), ET-1+RSG, ET-1+chelerythrine (che, the PKC inhibitor), PMA+RSG, or without treatment (control), respectively. The effects of RSG on the protein content, (3)H-leucine incorporation, PKC activity and C-fos protein expression were observed in the cardiac myocytes stimulated with ET-1 or PMA.
RESULTSAfter two days of culture, the intracellular protein content in ET-1 group and PMA group were increased by 15% (339-/+15 microg/ml) and 13% (329-/+14 microg/ml) as compared with the control cells (290-/+13 microg/ml), respectively (P<0.01). Compared with the ET-1 group, cells treated with ET-1+10(-8) mol/L RSG, ET-1+10(-7) mol/L RSG, and ET-1+che showed decreased intracellular protein content by 10% (303-/+14 microg/ml, P<0.05), 12% (292-/+11 microg/ml, P<0.05), and 13% (291-/+12 microg/ml, P<0.01), respectively. The intracellular protein content in PMA+10(-7) mol/LRSG group was decreased by 10% (P<0.05) in comparison with the PMA group. RSG inhibited protein synthesis enhancement and increased (3)H-leucine incorporation induced by ET-1 and PMA, and antagonized the effects of ET-1 and PMA in promoting PKC activity and c-fos protein expression in the myocytes.
CONCLUSIONThe inhibitory effect of RSG on ET-1- or PMA-induced myocyte hypertrophy is associated with PKC-c-fos pathway.
