Pro‐Survival Protein Kinase Cδ Signaling Cascades are Mediated by (−)‐Epigallocatechin Gallate (EGCG) Polyphenols

Abstract

We have previously demonstrated that the pro‐survival isoform of Protein Kinase C Delta VIII (PKCδVIII), forms complexes with ERK1/2 and Cyclin D1 and contributes to pro‐survival signaling cascades. Ultimately, neuronal death contributes to the Alzheimer’s Disease phenotype. Retinoic acid stimulation has proven to be effective in altering PKCδ signaling mechanisms involved in neuronal degeneration. (−)‐Epigallocatechin‐3‐gallate (EGCG), a polyphenol found naturally in green tea, serves as a potential treatment for neurodegenerative diseases. Properties of EGCG may control the expression of antioxidant enzymatic activity via PKCδ signaling. A synthetic, yet more stable and bioavailable, form of EGCG can be synthesized via peracetate protection (AcEGCG). The mediation of natural and synthetic EGCG on PKCδVIII signaling pathways has not yet been elucidated. This study sought to characterize the neuronal protection introduced by treating retinoic acid stimulated NT2 cells with EGCG and AcECGC. Retinoic acid stimulation induces alternative splicing of PKC, which leads to expression of the pro‐survival, PKCδVIII, isoform. A dosed response relationship between EGCG/AcEGCG (0–100 μM) treatment and activation of PKCδVIII signaling were considered. ERK1/2 and Cyclin D1 expression and complex formation with PKCδVIII were described. Studying the effectiveness EGCG polyphenols promotion of pro‐survival mechanisms in neurons may contribute to the development of neuroprotective therapeutic agents that could prevent neurodegenerative diseases such as Alzheimer’s Disease.