Key result
Hydrogen peroxide induced a 6.03-fold upregulation of Egr-1 mRNA in H9c2 cells, an effect that was ablated by inhibiting ERK and JNK signaling pathways.
In H9c2 cardiomyoblasts, hydrogen peroxide induces Egr-1 expression and nuclear accumulation via ERK and JNK signaling pathways.
One of the most significant insults that jeopardize cardiomyocyte homeostasis is a surge of reactive oxygen species (ROS) in the failing myocardium. Early growth response factor-1 (Egr-1) has been found to act as a transcriptional regulator in multiple biological processes known to exert deleterious effects on cardiomyocytes. We thus investigated the signaling pathways involved in its regulation by H2O2. Egr-1 mRNA levels were found to be maximally induced after 2 h in H2O2-treated H9c2 cells. Egr-1 respective response at the protein level, was found to be maximally induced after 2 h of treatment with 200 microM H2O2, remaining elevated for 6 h, and declining thereafter. H2O2-induced upregulation of Egr-1 mRNA and protein levels was ablated in the presence of agents inhibiting ERKs pathway (PD98059) and JNKs (SP600125, AS601245). Immunofluorescent experiments revealed H2O2-induced Egr-1 nuclear sequestration to be also ERK- and JNK-dependent. Overall, our results show for the first time the fundamental role of ERKs and JNKs in regulating Egr-1 response to H2O2 treatment in cardiac cells at multiple levels: mRNA, protein and subcellular distribution. Nevertheless, further studies are required to elucidate the specific physiological role of Egr-1 regarding the modulation of gene expression and determination of cell fate.
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Aggeli et al. (2010) studied Oxidative stress in cardiomyocytes (in vitro). Hydrogen peroxide (H2O2) vs. Untreated cells was evaluated on Egr-1 mRNA expression levels at 2 hours (6.03-fold induction, p=<0.001). Hydrogen peroxide induced a 6.03-fold upregulation of Egr-1 mRNA in H9c2 cells, an effect that was ablated by inhibiting ERK and JNK signaling pathways.
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