[Inhibitory effects of rosiglitazone against endothelin-1-induced proliferation of rat cardiac myocytes: the role of PKC-c-fos pathway].

Abstract

OBJECTIVE:

To 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.

METHODS:

In 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.

RESULTS:

After 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.

CONCLUSION:

The inhibitory effect of RSG on ET-1- or PMA-induced myocyte hypertrophy is associated with PKC-c-fos pathway.

• Authors: Xiao-Xing Zhu, Xiao-Lin Niu, Ding-Zhang Chen, Xiao-Dong Zhou, Jian-Ming Pei, Miao-Zhang Zhu, Jun Guo, Xiao-Ling Zhu, Wen-Qing Wang
• Journal: Nan fang yi ke da xue xue bao = Journal of Southern Medical University (Nan Fang Yi Ke Da Xue Xue Bao) Vol. 28 Issue 6 Pg. 1056-60 (Jun 2008) ISSN: 1673-4254 [Print] China
• PMID: 18583263 (Publication Type: Journal Article)

Chemical References

• Endothelin-1
• Hypoglycemic Agents
• Proto-Oncogene Proteins c-fos
• Thiazolidinediones
• Rosiglitazone
• Protein Kinase C
• Tetradecanoylphorbol Acetate

Topics

• 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
• Rosiglitazone
• Signal Transduction (drug effects)
• Tetradecanoylphorbol Acetate (pharmacology)
• Thiazolidinediones (pharmacology)