Inhibitory effect of ginsenoside Rb1 on calcineurin signal pathway in cardiomyocyte hypertrophy induced by prostaglandin F2alpha.
OBJECTIVE
To examine the antihypertrophic effect of ginsenoside Rb1 (Rb1) induced by prostaglandin F2alpha(PGF2alpha) in vitro and to investigate the possible mechanisms involved in the calcineurin (CaN) signal transduction pathway.


METHODS
The cardiomyocyte hypertrophy induced by PGF2alpha and the antihypertrophic effect of Rb1 were evaluated in primary culture by measuring the cell diameter, protein content, and atrial natriuretic peptide (ANP) mRNA expression. ANP and CaN mRNA expressions, CaN and its downstream effectors NFAT3 and GATA4 protein expressions, and the intracellular free Ca2+ concentration ([Ca2+]i) were assayed by RT-PCR, Western blot, and fluorescent determination using Fura 2/AM, respectively.


RESULTS
PGF2alpha (100 nmol/L) significantly increased the cardiomyocyte diameter, protein content and [Ca2+]i, and promoted ANP, CaN mRNA, and CaN/NFAT3/GATA4 protein expressions, which were inhibited by either Rb1 in a concentration-dependent manner (50, 100, and 200 microg/mL) or L-arginine (1 mmol/L). NG-nitro-L-arginine-methyl ester, a nitric oxide synthase inhibitor, could abolish the effects of L-arginine, but failed to change the effects of Rb1 in the experiments above.


CONCLUSIONS
The present data implicate that Rb1 attenuates cardiac hypertrophy, the underlying mechanism may be involved in the inhibition of the Ca2+-CaN signal transduction pathway.
Jiang
Qing-song
QS
Department of Pharmacology, Chongqing Medical University, Chongqing, China.
Huang
Xie-nan
XN
Yang
Gui-zhong
GZ
Jiang
Xiao-yan
XY
Zhou
Qi-xin
QX
D000818:Animals; D019703:Calcineurin / Q000235:genetics; D065095:Calcineurin Inhibitors; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000188:drug therapy*; D002478:Cells, Cultured; D015237:Dinoprost / Q000494:pharmacology*; D050991:GATA4 Transcription Factor / Q000235:genetics; D036145:Ginsenosides / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology; D050778:NFATC Transcription Factors / Q000235:genetics; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
D065095:Calcineurin Inhibitors; D050991:GATA4 Transcription Factor; C084365:Gata4 protein, rat; D036145:Ginsenosides; D050778:NFATC Transcription Factors; C442759:ginsenoside Rb1; D015237:Dinoprost; D019703:Calcineurin; D002118:Calcium