PUBLICATION
Erk-Creb pathway suppresses glutathione-S-transferase pi expression under basal and oxidative stress conditions in zebrafish embryos
- Authors
- Hrubik, J., Glisic, B., Fa, S., Pogrmic-Majkic, K., Andric, N.
- ID
- ZDB-PUB-151024-7
- Date
- 2016
- Source
- Toxicology letters 240(1): 81-92 (Journal)
- Registered Authors
- Keywords
- Akt, Erk, gstp1-2, oxidative stress, zebrafish embryos
- MeSH Terms
-
- Androstadienes/pharmacology
- Animals
- Butadienes/pharmacology
- Cyclic AMP Response Element-Binding Protein/genetics*
- Cyclic AMP Response Element-Binding Protein/metabolism
- Enzyme Inhibitors/pharmacology
- Extracellular Signal-Regulated MAP Kinases/genetics*
- Extracellular Signal-Regulated MAP Kinases/metabolism
- Gene Expression Regulation, Enzymologic*
- Glutathione S-Transferase pi/antagonists & inhibitors
- Glutathione S-Transferase pi/genetics*
- Glutathione S-Transferase pi/metabolism
- Hydroquinones/pharmacology
- Nitriles/pharmacology
- Oxidative Stress/drug effects*
- Phosphorylation
- Promoter Regions, Genetic
- Protein Kinase Inhibitors/pharmacology
- Proto-Oncogene Proteins c-akt/genetics
- Proto-Oncogene Proteins c-akt/metabolism
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Transcriptional Activation
- Zebrafish/embryology*
- Zebrafish/genetics
- PubMed
- 26494252 Full text @ Toxicol. Lett.
- CTD
- 26494252
Citation
Hrubik, J., Glisic, B., Fa, S., Pogrmic-Majkic, K., Andric, N. (2016) Erk-Creb pathway suppresses glutathione-S-transferase pi expression under basal and oxidative stress conditions in zebrafish embryos. Toxicology letters. 240(1):81-92.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping