Green tea polyphenol (–)‐epigallocatechin‐3‐gallate induces neurorescue of long‐term serum‐deprived PC12 cells and promotes neurite outgrowth

• Published in: Journal of neurochemistry 2005-06, Vol.93 (5), p.1157-1167
• Main Authors: Reznichenko, L., Amit, T., Youdim, M. B. H., Mandel, S.
• Format: Article
• Language: English
• Subjects: (–)‐epigallocatechin‐3‐gallate; Amino acids; Animals; Biological and medical sciences; Biological Transport - drug effects; Catechin - analogs & derivatives; Catechin - pharmacology; Cell Death - drug effects; Cell Differentiation - drug effects; Cell Membrane - enzymology; Central nervous system; Culture Media, Serum-Free - pharmacology; differentiation; Electrophysiology; Enzyme Activation - drug effects; Flavonoids - pharmacology; Fundamental and applied biological sciences. Psychology; Inhibitor drugs; Isolated neuron and nerve. Neuroglia; Neurites - drug effects; Neurites - physiology; neurodegenerative diseases; Neurons; Neuroprotective Agents - pharmacology; neurorescue; PC12 Cells - drug effects; PC12 Cells - enzymology; PC12 Cells - pathology; PC12 Cells - physiology; Phenols - pharmacology; polyphenol; Polyphenols; protein kinase C; Protein Kinase C - metabolism; Protein Kinase C - physiology; Protein Kinase C-alpha; Proteins; Rats; Tea; Vertebrates: nervous system and sense organs
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2005.03085.x

Our previous studies have shown that the green tea polyphenol (–)‐epigallocatechin‐3‐gallate (EGCG) prevents neuronal cell death caused by several neurotoxins. The present study sought to determine the neuroprotective effect of EGCG when it is administered after the induction of cell damage (‘neurorescue’). In an attempt to imitate a progressive mode of death, PC12 cells were initially subjected to serum‐starvation conditions for a period of 1 or 3 days before administration of EGCG (0.1–10 µm) for up to 3 days. In spite of the high percentage of cell death, single or repetitive administration of EGCG (1 µm) significantly attenuated cell death. The neurorescue effect of EGCG was abolished by pre‐treatment with the protein kinase C inhibitor GF109203X (2.5 µm), suggesting the involvement of the protein kinase C pathway in neurorescue by the drug. This is consistent with the rapid (15 min) translocation of the protein kinase C alpha isoform to the cell membrane in response to EGCG. The correlative neurite outgrowth activity of EGCG on PC12 cells may also contribute to its neurorescue effect. The present findings suggest that EGCG may have a positive impact on aging and neurodegenerative diseases to retard or perhaps even reverse the accelerated rate of neuronal degeneration.