L-Theanine Effectively Protects Against Copper-Facilitated Dopamine Oxidation: Implication for Relieving Dopamine Overflow-Associated Neurotoxicities.

Non-physiological disorders release dopamine into extracellular brain fluid to induce neurodegenerative brain diseases. The harmful mechanism of dopamine overflow is attributed to the dopamine-mediated production of hydroxyl radicals, suggesting that transition metal copper which is high in the brain is involved in promoting dopamine oxidation. MPP+ , an intermediate formed from the conversion of MPTP, is one of the most potent dopamine-releasing agents. It has been reported that L-theanine could improve motor dysfunction in MPTP-treated mice, suggesting that L-theanine may restrain copper-mediated oxidation of released dopamine. The present study examined the influences of L-theanine on extracellular dopamine-mediated cytotoxicity in the absence and presence of copper in SH-SY5Y cells. L-theanine significantly but only moderately suppressed cytotoxicity caused by dopamine alone. Surprisingly, dopamine together with copper rapidly and dramatically caused apoptotic responses by massively disrupting redox homeostasis. Nonetheless, L-theanine exhibited an extraordinary protective effect against these devastating events by chelating copper. The above great contrast in terms of copper could be recapitulated in a cell-free system. Though L-theanine reduced dopamine autoxidation as detected by HPLC, the capacity was not impressive, since a molar ratio of 10,000 (L-theanine to dopamine) was required for fully suppressing dopamine decrease. However, HPLC measurement showed that L-theanine was highly efficient in suppressing copper-mediated dopamine oxidation because only a molar ratio of 10 was required for fully suppressing dopamine decrease. Since copper plays a crucial role in promoting extracellular dopamine oxidation, our results suggest that L-theanine by chelating copper is an attractive food-based protective agent against dopamine overflow.