Erk-Creb pathway suppresses glutathione-S-transferase pi expression under basal and oxidative stress conditions in zebrafish embryos.
Transcriptional activation of phase II enzymes including glutathione-S-transferase pi class (Gst Pi) is important for redox regulation and defense from xenobiotics. The role of extracellular signal-regulated kinase (Erk) and protein kinase B (Akt) in regulation of Gst Pi expression has been described using adult mammalian cells. Whether these signaling pathways contribute to Gst Pi expression during embryogenesis is unknown. Using zebrafish embryo model, we provide novel evidence that Erk signaling acts as a specific suppressor of gstp1-2 mRNA during early embryogenesis. Addition of Erk inhibitor U0126 enhanced gstp1-2 mRNA expression during transition from blastula to the segmentation stage and from pharyngula until the hatching stage. Basal Erk activity did not affect gstp1-2 expression in tert-butylhydroquinone-exposed embryos. Addition of phorbol 12-myristate 13-acetate increased Erk activity leading to suppression of gstp1-2 mRNA. Activation of cAMP/Creb pathway by forskolin prevented gstp1-2 expression, whereas U0126 suppressed Creb phosphorylation, thus setting up Creb as a proximal transmitter of Erk inhibitory effect. Collectively, these findings suggest that Erk-Creb pathway exerts suppressive effect on gstp1-2 mRNA in a narrow developmental window. This study also provides a novel link between Erk and gstp1-2 expression, setting apart a possible differential regulation of gstp1-2 in adult and embryonic cells.
Laboratory for Ecotoxicology, Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia.
Jelena
J
Hrubik
Laboratory for Ecotoxicology, Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia.
Branka
B
Glisic
Laboratory for Ecotoxicology, Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia.
Svetlana
S
Fa
Laboratory for Ecotoxicology, Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia.
Kristina
K
Pogrmic-Majkic
Laboratory for Ecotoxicology, Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia. Electronic address: nebojsa.andric@dbe.uns.ac.rs.
Nebojsa
N
Andric
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D051549:Glutathione S-Transferase pi / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006873:Hydroquinones / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D000077191:Wortmannin; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics
D000730:Androstadienes; D002070:Butadienes; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D006873:Hydroquinones; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; C113580:U 0126; C018855:2-tert-butylhydroquinone; D051549:Glutathione S-Transferase pi; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D000077191:Wortmannin
Akt; Erk; Oxidative stress; Zebrafish embryos; gstp1–2