Relation of Cardiotrophin-1 (CT-1) and cardiac transcription factor GATA4 expression in rat's cardiac myocytes hypertrophy and apoptosis.

Abstract

The aim of this study was to evaluate the role of GATA4 in hypertrophy and survival functions of CT-1 in the heart, and to apply chemical inhibitor strategies to assess a possible interaction of signaling pathways involved in these processes. Expression of GATA4 was determined at the mRNA expression (polymerase chain reaction, PCR) and protein binding activity (electrophoretic mobility shift assays, EMSAs) levels. Myocardial apoptosis was detected using the in-situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. Parthenolide (an inhibitor to STAT3) and U0126 (an MEK inhibitor to block ERK1/2) were used to assess a possible interaction of signaling pathways involved in the processes. The results showed that CT-1 had a significant role in the expression of GATA4 mRNA and binding activity of cardiomyocytes. The stronger expression of GATA4 mRNA stimulated by CT-1 was essentially mediated by STAT3, and was negatively regulated by ERK1/2. The intercross relationship between STAT3 and ERK1/2 might assist CT-1 in cardiac hypertrophy. At the same time, CT-1 had its effect on anti-apoptosis and survival of cardiac myocytes. During this process, GATA4 expression showed a negative relationship with myocardial apoptosis. Obviously, STAT3 cannot affect the anti-apoptotic process of CT-1, but obstruction of ERK signaling pathway can inhibit the CT-1 anti-apoptotic effect significantly. Our data suggest that CT-1 can affect the expression of GATA4 mRNA and the binding activity of cardiac myocytes. GATA4 plays an important role in the hypertrophic effect of CT-1, in which STAT3 plays a primary role. The regulation of CT-1 on the anti-apoptotic process is mediated partly by GATA4, and can be inhibited by obstructing the ERK signaling pathway.

• Authors: Zhao He-nan, Wang Yan, Jiang Miao-na, Zhang Cai-hua, Li Shen, Jia Yu-jie
• Journal: Pathology, research and practice (Pathol Res Pract) Vol. 205 Issue 9 Pg. 615-25 ( 2009) ISSN: 1618-0631 [Electronic] Germany
• PMID: 19327894 (Publication Type: Journal Article)

Chemical References

• Cytokines
• GATA4 Transcription Factor
• Gata4 protein, rat
• RNA, Messenger
• STAT3 Transcription Factor
• Stat3 protein, rat
• cardiotrophin 1
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3

Topics

• Animals
• Apoptosis (physiology)
• Cardiomegaly (metabolism, pathology)
• Cells, Cultured
• Cytokines (metabolism)
• Electrophoretic Mobility Shift Assay
• GATA4 Transcription Factor (metabolism)
• Immunohistochemistry
• In Situ Nick-End Labeling
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Myocytes, Cardiac (metabolism, pathology)
• RNA, Messenger (analysis)
• Rats
• Rats, Sprague-Dawley
• Reverse Transcriptase Polymerase Chain Reaction
• STAT3 Transcription Factor (metabolism)
• Signal Transduction (physiology)