Regular Article
Geranylgeranylacetone Enhances Expression of Thioredoxin and Suppresses Ethanol-Induced Cytotoxicity in Cultured Hepatocytes

https://doi.org/10.1006/bbrc.2000.3392Get rights and content

Abstract

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-κB, 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-κB and AP-1.

References (26)

  • T. Kurihara et al.

    Increase in hepatic tissue blood flow by teprenone

    J. Gastroenterol. Hepatol.

    (1996)
  • A. Holmgren

    Thioredoxin and glutaredoxin systems

    J. Biol. Chem.

    (1989)
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