Inhibitiory effect of trilinolein on endothelin-1-induced c-fos gene expression in cultured neonatal rat cardiomyocytes

Trilinolein, isolated from the traditional Chinese
herb Sanchi (Panax notoginseng), has been shown to have
myocardial protective effects via its antioxidant ability.
However, the cellular and molecular mechanisms of the
protective effect of trilinolein in the heart remain to be
elucidated. Oxidative mechanisms have been implicated in
neonatal cardiomyocyte hypertrophy. We previously reported
that ET-1 induces ROS generation via the ETA
receptor and ROS modulates c-fos gene expression. We
have therefore examined whether trilinolein attenuates
ROS production and ET-1-induced c-fos gene expression in
cardiomyocytes. Cultured neonatal rat cardiomyocytes
were stimulated with ET-1 (10 nM), and c-fos gene expression
was examined. Trilinolein (1 and 10 μM)
inhibited ET-1-induced c-fos gene expression in cardiomyocytes.
We also examined the effects of trilinolein on
ET-1- increased NADPH oxidase activity and superoxide
formation. Trilinolein inhibited ET-1-increased NADPH
oxidase activity and superoxide formation in a concentration-
dependent manner. This increase in superoxide
production by ET-1 was significantly inhibited by trilinolein,
diphenyleneiodonium, or N-acetylcysteine. Trilinolein
also decreased ET-1- or H2O2-induced extracellular signalregulated
kinase (ERK) phosphorylation, c-Jun NH2-
terminal kinase (JNK) phosphorylation, and activator
protein-1 activation. These data indicate that trilinolein
inhibits ET-1-induced ERK phosphorylation, JNK phosphorylation,
and c-fos gene expression via attenuating
superoxide production in cardiomyocytes.
Keywords Trilinolein . Endothelin-1 . Cardiomyocyte
hypertrophy . Superoxide . Signal transduction .
Gene expression