Epigallocatechin gallate prevents oxidative-stress-induced death of mutant Cu/Zn-superoxide dismutase (G93A) motoneuron cells by alteration of cell survival and death signals

Seong Ho Koh, Hyugsung Kwon, Kyung Suk Kim, Juhan Kim, Myung Ho Kim, Hyun Jeung Yu, Manho Kim, Kwang Woo Lee, Byung Rok Do, Hai Kwan Jung, Ki Wha Yang, Stanley H. Appel, Seung H. Kim

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

This study was undertaken to evaluate the effect of the G93A mutation in the human Cu/Zn-superoxide dismutase gene (hSOD1) on the phosphatidylinositol-3- kinase (PI3K)/Akt and glycogen synthase kinase-3 (GSK-3) pathway in motoneuron, and to determine the role of epigallocatechin gallate (EGCG) on oxidative stress-injured motoneurons. The viability of G93A mutant cells was less than that of wild-type cells, and the activation of PI3K and the phosphorylation of Akt and GSK-3 in G93A mutant cells decreased compared with wild-type hSOD1 4.1 cells. In the experiment to evaluate the effect of oxidative stress and/or EGCG on these motoneurons, after exposure to 400 μM H 2O 2, the MTT assay revealed greatly reduced viability of G93A mutant cells compared with wild-type cells, and pre-treatment of these cells with EGCG before H 2O 2 exposure increased the viability of both cell lines. Western blot analysis showed that the G93A mutation and oxidative stress decreased survival signals including PI3K/Akt but increased death signals including GSK-3; however, pre-treatment with EGCG increased survival signals but decreased death signals. These results suggest that PI3K/Akt and GSK-3 activities are altered in G93A mutant cells and EGCG-induced activation of PI3K/Akt and inhibition of GSK-3 could be a new potential therapeutic strategy for ALS associated with oxidative injury.

Original languageEnglish (US)
Pages (from-to)213-225
Number of pages13
JournalToxicology
Volume202
Issue number3
DOIs
StatePublished - Oct 1 2004

Keywords

  • Epigallocatechin gallate
  • Motoneuron
  • Oxidative stress
  • Survival and death signals

ASJC Scopus subject areas

  • Toxicology

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