Geranylgeranylacetone enhances expression of thioredoxin and suppresses ethanol-induced cytotoxicity in cultured hepatocytes

Biochem Biophys Res Commun. 2000 Sep 7;275(3):825-30. doi: 10.1006/bbrc.2000.3392.


Geranylgeranylacetone (GGA) has been introduced into the clinical field as an anti-ulcer drug. In addition to protective effects on gastric mucosal cells, GGA also has anti-apoptotic effects against ischemia and reperfusion injury in hepatocytes and intestinal cells. However, the molecular mechanisms of the cytoprotective or anti-apoptotic effect of GGA are largely unknown. To explore the molecular mechanism of GGA action, we focused on thioredoxin (TRX), an endogenous-redox-acting molecule. We have demonstrated that GGA induces the messenger RNA and protein of TRX and affects the activation of transcription factors, AP-1 and NF-kappaB, and that GGA blunted ethanol-induced cytotoxicity of cultured hepatocytes. These results provide evidence suggesting that a possible novel molecular mechanism of GGA is to protect cells via the induction of TRX and the activation of transcription factors such as NF-kappaB and AP-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Ulcer Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line
  • Cells, Cultured
  • Diterpenes / pharmacology*
  • Ethanol / antagonists & inhibitors*
  • Ethanol / toxicity
  • Gene Expression Regulation / drug effects
  • Genes, Reporter
  • Humans
  • Liver / cytology
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • NF-kappa B / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tetradecanoylphorbol Acetate / pharmacology
  • Thioredoxins / genetics
  • Thioredoxins / metabolism*
  • Transcription Factor AP-1 / metabolism
  • Transfection
  • Tumor Necrosis Factor-alpha / pharmacology


  • Anti-Ulcer Agents
  • Diterpenes
  • NF-kappa B
  • RNA, Messenger
  • Transcription Factor AP-1
  • Tumor Necrosis Factor-alpha
  • Ethanol
  • Thioredoxins
  • Tetradecanoylphorbol Acetate
  • geranylgeranylacetone