Genomics & Informatics

Korea Genome Organization (한국유전체학회)
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High-concentration Epigallocatechin Gallate Treatment Causes Endoplasmic Reticulum Stress-mediated Cell Death in HepG2 Cells

  • Ahn, Joon-Ik (Molecular Pharmacology Division, Pharmacological Research Department, National Institute of Toxicological Research) ;
  • Jeong, Kyoung-Ji (Molecular Pharmacology Division, Pharmacological Research Department, National Institute of Toxicological Research) ;
  • Ko, Moon-Jeong (Molecular Pharmacology Division, Pharmacological Research Department, National Institute of Toxicological Research) ;
  • Shin, Hee-Jung (Molecular Pharmacology Division, Pharmacological Research Department, National Institute of Toxicological Research) ;
  • Chung, Hye-Joo (Molecular Pharmacology Division, Pharmacological Research Department, National Institute of Toxicological Research) ;
  • Jeong, Ho-Sang (Molecular Pharmacology Division, Pharmacological Research Department, National Institute of Toxicological Research)
  • Published : 2009.06.30
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Abstract

Epigallocatechin gallate (EGCG), a well-known antioxidant molecule, has been reported to cause hepatotoxicity when used in excess. However, the mechanism underlying EGCG-induced hepatotoxicity is still unclear. To better understand the mode of action of EGCG-induced hepatotoxicity, we examined the effect of EGCG on human hepatic gene expression in HepG2 cells using microarrays. Analyses of microarray data revealed more than 1300 differentially expressed genes with a variety of biological processes. Upregulated genes showed a primary involvement with protein-related biological processes, such as protein synthesis, protein modification, and protein trafficking, while downregulated genes demonstrated a strong association with lipid transport. Genes involved in cellular stress responses were highly upregulated by EGCG treatment, in particular genes involved in endoplasmic reticulum (ER) stress, such as GADD153, GADD34, and ATF3. In addition, changes in genes responsible for cholesterol synthesis and lipid transport were also observed, which explains the high accumulation of EGCG-induced lipids. We also identified other regulatory genes that might aid in clarifying the molecular mechanism underlying EGCG-induced hepatotoxicity.

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References

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