ERKs and JNKs Mediate Hydrogen Peroxide-Induced Egr-1 Expression and Nuclear Accumulation in H9c2 Cells

作者：Aggeli I K S; Beis I; Gaitanaki C^*

来源：Physiological Research, 2010, 59(3): 443-454.

DOI：10.33549/physiolres.931806

• Early growth response factor-1 (Egr-1)
• ERKs
• JNKs
• H(2)O(2)
• Signaling

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 H(2)O(2). Egr-1 mRNA levels were found to be maximally induced after 2 h in H(2)O(2)-treated H9c2 cells. Egr-1 respective response at the protein level, was found to be maximally induced after 2 h of treatment with 200 mu M H(2)O(2), remaining elevated for 6 h, and declining thereafter. H(2)O(2)-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 H(2)O(2)-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 H(2)O(2) 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.

• 出版日期2010