Open AccessERKs and JNKs Mediate Hydrogen Peroxide-Induced Egr-1 Expression and Nuclear Accumulation in H9c2 Cells
Author(s) -
Ioanna Katerina Aggeli,
Isidoros Beis,
Catherine Gaitanaki
Publication year - 2010
Publication title -
physiological research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.647
H-Index - 70
eISSN - 1802-9973
pISSN - 0862-8408
DOI - 10.33549/physiolres.931806
Subject(s) - downregulation and upregulation , microbiology and biotechnology , reactive oxygen species , regulator , chemistry , hydrogen peroxide , mapk/erk pathway , messenger rna , homeostasis , signal transduction , gene expression , biology , biochemistry , gene
One of the most significant insults that jeopardize cardiomyocytehomeostasis is a surge of reactive oxygen species (ROS) in thefailing myocardium. Early growth response factor-1 (Egr-1) hasbeen found to act as a transcriptional regulator in multiplebiological processes known to exert deleterious effects oncardiomyocytes. We thus investigated the signaling pathwaysinvolved in its regulation by H2O2. Egr-1 mRNA levels were foundto be maximally induced after 2 h in H2O2-treated H9c2 cells.Egr-1 respective response at the protein level, was found to bemaximally induced after 2 h of treatment with 200 μM H2O2,remaining elevated for 6 h, and declining thereafter. H2O2-induced upregulation of Egr-1 mRNA and protein levels wasablated in the presence of agents inhibiting ERKs pathway(PD98059) and JNKs (SP600125, AS601245). Immunofluorescentexperiments revealed H2O2-induced Egr-1 nuclear sequestrationto be also ERK- and JNK-dependent. Overall, our results show forthe first time the fundamental role of ERKs and JNKs inregulating Egr-1 response to H2O2 treatment in cardiac cells atmultiple levels: mRNA, protein and subcellular distribution.Nevertheless, further studies are required to elucidate thespecific physiological role of Egr-1 regarding the modulation ofgene expression and determination of cell fate.