PUBLICATION

Lithium promotes the production of reactive oxygen species via GSK-3β/TSC2/TOR signaling in the gill of zebrafish (Danio rerio)

Authors
Liu, D., Gao, L., Zhang, Z., Tao, S., Pang, Q., Li, A., Deng, H., Yu, H.
ID
ZDB-PUB-180102-7
Date
2017
Source
Chemosphere   195: 854-863 (Journal)
Registered Authors
Keywords
Danio rerio, Glycogen synthase kinase-3β, Lithium, Reactive oxygen species, Target of rapamycin, Tuberous sclerosis complex 2
MeSH Terms
  • Animals
  • Catalase/genetics
  • Catalase/metabolism
  • Gills/drug effects*
  • Gills/metabolism
  • Glutathione Peroxidase/genetics
  • Glutathione Peroxidase/metabolism
  • Glycogen Synthase Kinase 3 beta/genetics
  • Glycogen Synthase Kinase 3 beta/metabolism
  • Hydrogen Peroxide/metabolism
  • Intracellular Signaling Peptides and Proteins/genetics
  • Intracellular Signaling Peptides and Proteins/metabolism
  • Lithium/pharmacology*
  • Membrane Potential, Mitochondrial/drug effects
  • Reactive Oxygen Species/metabolism*
  • Signal Transduction/drug effects
  • Superoxide Dismutase/genetics
  • Superoxide Dismutase/metabolism
  • TOR Serine-Threonine Kinases/genetics
  • TOR Serine-Threonine Kinases/metabolism
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
29291576 Full text @ Chemosphere
Abstract
In this study, the mechanism that lithium (Li) promotes the production of reactive oxygen species (ROS) via the glycogen synthase kinase-3β (GSK-3β)/tuberous sclerosis complex 2 (TSC2)/target of rapamycin (TOR) signaling was investigated in the gill of zebrafish (Danio rerio). After the zebrafish were treated by 25 and 50 mg/L Li+, the mRNA expression of GSK-3β and TSC2 was inhibited, but the expression of TOR was induced in the gill of zebrafish. 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), glutathione peroxidase (GSH-PX), and peroxidase (POD) were decreased by 25 and 50 mg/L Li+ treatments. In the ZF4 cells, the mRNA expression of GSK-3β and TSC2 was inhibited, but TOR expression was induced by 1, 5, and 10 mmol/L Li+ treatments. To further confirm that lithium promoted ROS production via GSK-3β inhibition, GSK-3β RNA was interfered. It was found that the interference of GSK-3β RNA induced the TSC2/TOR signaling. The levels of H2O2, O2·-, and ·OH were increased, but the activities of CAT, GSH-PX, and POD were decreased by GSK-3β RNA interference. In addition, lithium decreased the mitochondrial membrane potential (MMP) with Rhodamine-123 assay, but increased the levels of ROS by 2',7'-dichlorofluorescein diacetate (DCFH-DA) assay. The present results indicated that lithium promoted the ROS production through the GSK-3β/TSC2/TOR signaling in the gill of zebrafish.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping