[Effect of cardiotrophin-1 on cardiac transcription factor GATA4 expression in rat cardiomyocytes].
OBJECTIVE
To investigate the effect of cardiotrophin-1 (CT-1) on the GATA4 expression and related signaling pathways (JAK-STAT3, ERK1/2 and PI3-K) in rat cardiomyocytes.


METHODS
Using semi-quantitative RT-PCR and EMSA, we measured the dose and time dependent effects of CT-1 on GATA4 mRNA and binding activity in cultured rat cardiomyocytes. Parthenolide (a STAT inhibitor), U-0126 (an ERK inhibitor) and LY-294002 (a PI3-K inhibitor) alone or in combination were added to the culture medium to assess the role of above signaling pathways in CT-1 mediated effects.


RESULTS
GATA4 mRNA expression significantly increased at 3 h post 0.1 nmol/L CT-1 exposure, peaked at 6 h and remained high till 24 h post exposure. The GATA4 binding activity began to increase at 10 min and peaked at 60 min and returned to baseline level 180 min. Six hours post CT-1 (0.01 nmol/L, 0.1 nmol/L, 1 nmol/L) exposure, the GATA4 mRNA expression increased in a dose-dependent manner. The GATA4 binding activity peaked with 0.1 nmol/L CT-1 and higher dose did not further increase the binding activity. U-0126 increased the GATA4 mRNA expression and enhanced the GATA4 binding activity and these effects could be partially attenuated with addition of Parthenolide. Parthenolide also prevented the increase of GATA4 mRNA and binding activity induced by CT-1. LY-294002 had no effects GATA4 mRNA and binding activity.


CONCLUSIONS
CT-1 increases the GATA4 mRNA expression and binding activity in rat cardiomyocytes via STAT3/ERK1/2 pathways and these effects are independent of PI3-K pathway.
Zhao
He-Nan
HN
Department of Pathophysiology of Dalian Medical University, Dalian 116027, China.
Wang
Yan
Y
Li
Shen
S
Jiang
Miao-Na
MN
Tang
Jian-He
JH
Jia
Yu-Jie
YJ
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D050991:GATA4 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D032383:Myocytes, Cardiac / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000494:pharmacology; D015398:Signal Transduction
D016207:Cytokines; D050991:GATA4 Transcription Factor; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C092073:cardiotrophin 1