ERKs and JNKs mediate hydrogen peroxide-induced Egr-1 expression and nuclear accumulation in H9c2 cells
Language English Country Czech Republic Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
19681663
DOI
10.33549/physiolres.931806
PII: 931806
Knihovny.cz E-resources
- MeSH
- Active Transport, Cell Nucleus MeSH
- Cell Nucleus drug effects enzymology MeSH
- Cell Line MeSH
- Time Factors MeSH
- Extracellular Signal-Regulated MAP Kinases antagonists & inhibitors metabolism MeSH
- Fluorescent Antibody Technique MeSH
- Protein Kinase Inhibitors pharmacology MeSH
- JNK Mitogen-Activated Protein Kinases antagonists & inhibitors metabolism MeSH
- Myocytes, Cardiac drug effects enzymology MeSH
- Rats MeSH
- RNA, Messenger metabolism MeSH
- Hydrogen Peroxide pharmacology MeSH
- Early Growth Response Protein 1 genetics metabolism MeSH
- Up-Regulation MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Egr1 protein, rat MeSH Browser
- Extracellular Signal-Regulated MAP Kinases MeSH
- Protein Kinase Inhibitors MeSH
- JNK Mitogen-Activated Protein Kinases MeSH
- RNA, Messenger MeSH
- Hydrogen Peroxide MeSH
- Early Growth Response Protein 1 MeSH
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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