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 language | English (US) |
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Pages (from-to) | 213-225 |
Number of pages | 13 |
Journal | Toxicology |
Volume | 202 |
Issue number | 3 |
DOIs | |
State | Published - Oct 1 2004 |
Keywords
- Epigallocatechin gallate
- Motoneuron
- Oxidative stress
- Survival and death signals
ASJC Scopus subject areas
- Toxicology