Cytoprotective Effect of Epigallocatechin gallate (EGCG) in Oxidative-stressed PC12 Cells Following H2O2 Exposure-Effect of EGCG on

Background: Neurodegenerative diseases (ND) are associated with oxidative stress, and antioxidants including epi-gallocatechin gallate (EGCG) have been tried as potential therapeutic regimens of an experimental model of ND. We performed this study to determine the neuroprotective role of EGCG on up stream and down stream signals in oxida-tive-stress-injured PC12 cells by exposing them to H2O2. Methods: Following 100 μM H2O2 exposure, the viability of PC12 cells (not pretreated vs EGCG or z-VAD-fmk pretreated) was evaluated by using a MTT assay. Immunoreactivity (IR) of cytochrome c, caspase-3, poly (ADP-ribose) polymerase (PARP), PI3K/Akt and GSK-3 was examined by using a Western blot. Results: EGCG or z-VAD-fmk pretreated PC12 cells showed increased viability. Dose-dependent inhi-bition of caspase-3 activation and PARP cleavage was demonstrated by the pretreatment of both agents. However, the inhibition of cytochrome c release was only detected in EGCG pretreated cells. On the pathway through PI3K/Akt and GSK-3, however, the result of a western blot in EGCG pretreated cells showed decreased IR of Akt and GSK-3 and increased IR of p85a PI3K, phosphorylated Akt and GSK-3, and contrasted with that in z-VAD-fmk pretreated cells showing no changes. Conclusions: These data show that EGCG affects apoptotic pathways through upstream signals including PI3K/Akt and GSK-3 pathways as well as downstream signals including cytochrome c and caspase-3 path