Protein Kinase C-mediated Neuroprotective Action of (-)-epigallocatechin-3-gallate against $A{\beta}_{1-42}$-induced Apoptotic Cell Death in SH-SY5Y Neuroblastoma Cells

다국어 초록 (Multilingual Abstract)

The neurotoxicity of amyloid $\beta(A\beta)$ is associated with an increased production of reactive oxygen species and apoptosis, and it has been implicated in the development of Alzheimer's disease. While(-)-epigallocatechin-3-gallate(EGCG) suppresses $A\beta$-induced apoptosis, the mechanisms underlying this process have yet to be completely clarified. This study was designed to investigate whether EGCG plays a neuroprotective role by activating cell survival system such as protein kinase C(PKC), extracellular-signal-related kinase(ERK), c-Jun N-terminal kinase(JNK), and anti-apoptotic and pro-apoptotic genes in SH-SY5Y human neuroblastoma cells. One ${\mu}M\;A{\beta}_{1-42}$ decreased cell viability, which was correlated with increased DNA fragmentation evidenced by DAPI staining. Pre-treatment of SH-SY5Y neuroblastoma cells with EGCG($1{\mu}M$) significantly attenuated $A{\beta}_{1-42}$-induced cytotoxicity. Potential cell signaling candidates involved in this neuroprotective effects were further examined. EGCG restored the reduced PKC, ERK, and JNK activities caused by $A{\beta}_{1-42}$ toxicity. In addition, gene expression analysis revealed that EGCG prevented both the $A{\beta}_{1-42}$-induced expression of a pro-apoptotic gene mRNA, Bad and Bax, and the decrease of an anti-apoptotic gene mRNA, Bcl-2 and Bcl-xl. These results suggest that the neuroprotective mechanism of EGCG against $A{\beta}_{1-42}$-induced apoptotic cell death includes stimulation of PKC, ERK, and JNK, and modulation of cell survival and death genes.