Protein Kinase C-mediated Neuroprotective Action of (－)-epigallocatechin-3-gallate against Aβ<SUB>1-42</SUB>-induced Apoptotic Cell Death in SH-SY5Y Neuroblastoma Cells

Protein Kinase C-mediated Neuroprotective Action of (－)-epigallocatechin-3-gallate against Aβ<SUB>1-42</SUB>-induced Apoptotic Cell Death in SH-SY5Y Neuroblastoma Cells

The neurotoxicity of amyloid β (Aβ) 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 Aβ-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 μM Aβ<SUB>1-42</SUB> decreased cell viability, which was correlated with increased DNA fragmentation evidenced by DAPI staining. Pre-treatment of SH-SY5Y neuroblastoma cells with EGCG (1μM) significantly attenuated Aβ1-42-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 Aβ<SUB>1-42 </SUB>toxicity. In addition, gene expression analysis revealed that EGCG prevented both the Aβ<SUB>1-42</SUB>-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 Aβ<SUB>1-42</SUB>-induced apoptotic cell death includes stimulation of PKC, ERK, and JNK, and modulation of cell survival and death genes.