J Korean Neurol Assoc > Volume 21(4); 2003 > Article

Journal of the Korean Neurological Association 2003;21(4): 392-400.

"PC12 세포의 산화성 손상에 대한 Epigallocatechin gallate (EGCG)의 세포보호효과 - EGCG가 Phosphoinositide 3-kinase/Akt 및 Glycogen synthase kinase-3경로에 미치는 효과"

고성호 , "김승현§ 권혁성* 송치원* 김주환* 김주한§ 정@부§ 김명호§ 공@구‡ 유현정† 정해관*"

"식품의약품안전청 국립독성연구원 일반독성부 신경독성과학교실*, 분당제생병원 신경과학교실† 한양대학교 의과대학 병리학교실‡, 신경과학교실§"

"Cytoprotective Effect of Epigallocatechin gallate (EGCG) in Oxidative-stressed PC12 Cells Following H2O2 Exposure-Effect of EGCG on Phosphoinositide 3-kinase/Akt and Glycogen Synthase Kinase-3 Pathway"

Seong-Ho Koh

"Department of General Toxicology, National Institute of Toxicological Research, KFDA* Department of Neurology, Pundang Jaesaeng Hospital† Department of Pathology‡ and Neurology§, College of Medicine, Hanyang University"

Abstract

"Background: Neurodegenerative diseases (ND) are associated with oxidative stress, and antioxidants including epigallocatechin 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 oxidative- 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 G나-3 was examined by using a Western blot.
Results: EGCG or z-VAD-fmk pretreated PC12 cells showed increased viability. Dose-dependent inhibition 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 G나-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 pathways. Therefore, these results suggest that EGCG mediated activation of PI3K/Akt and inhibition GSK-3 could be a new protective mechanism on the pathogenesis of ND. Key Words: Apoptosis, Neurodegenerative disease, Antioxidants, Glycogen synthase kinase 3, PI3K, Akt"