The inhibition of GSK-3β promotes the production of reactive oxygen species via β-catenin/C/EBPα signaling in the spleen of zebrafish (Danio rerio)

Fish Shellfish Immunol. 2018 May:76:110-120. doi: 10.1016/j.fsi.2018.02.040. Epub 2018 Mar 2.

Abstract

In this study, the mechanism that the inhibition of glycogen synthase kinase-3β (GSK-3β) promotes the production of reactive oxygen species (ROS) via β-catenin/CCAAT/enhancer binding protein α (C/EBPα) signaling was investigated in the spleen of zebrafish (Danio rerio). The results demonstrated that the inhibition of GSK-3β induced the mRNA expression of β-catenin and C/EBPα by lithium (Li) treatments or GSK-3β RNA interference. The levels of hydrogen peroxide (H2O2), superoxide anion (O2.-), and hydroxy radical (·OH) as well as the activity of superoxide dismutase (SOD) were increased, while the activities of catalase (CAT) and glutathione peroxidase (GSH-PX) were decreased in the spleen and ZF4 cells of zebrafish by Li+ treatments. In addition, GSK-3β RNA interference increased ROS levels and decreased the activities of CAT and GSH-PX in the spleen. The fluorescence intensity of ROS was increased but the mitochondrial membrane potential (MMP) was decreased by Li+ treatments in ZF4 cells labeled with 2',7'-dichlorofluorescein diacetate (DCFH-DA) and Rhodamine-123, respectively. The results of present study indicated that the inhibition of GSK-3β promoted the ROS production via β-catenin/C/EBPα signaling in the spleen of zebrafish, and the balance between ROS and antioxidants could be destroyed by the GSK-3β/β-catenin/C/EBPα signaling. The results may be a valuable contribution to understanding the modulatory mechanism of GSK-3β/β-catenin/C/EBPα signaling on the antioxidant system in fish species.

Keywords: CCAAT/Enhancer binding protein α; Danio rerio; Glycogen synthase kinase-3β; Reactive oxygen species; β-catenin.

MeSH terms

  • Animals
  • CCAAT-Enhancer-Binding Protein-alpha / genetics
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism
  • Fish Proteins / antagonists & inhibitors*
  • Fish Proteins / genetics
  • Fish Proteins / metabolism
  • Glycogen Synthase Kinase 3 beta / antagonists & inhibitors*
  • Lithium / adverse effects
  • Random Allocation
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction*
  • Spleen / immunology*
  • Zebrafish / genetics*
  • Zebrafish / immunology*
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • CCAAT-Enhancer-Binding Protein-alpha
  • Fish Proteins
  • Reactive Oxygen Species
  • beta Catenin
  • Lithium
  • Glycogen Synthase Kinase 3 beta