title: Green tea catechins potentiate the neuritogenic action of brain-derived neurotrophic factor: role of 67-kDa laminin receptor and hydrogen peroxide.
abstract: Delivery of optimal amounts of brain-derived neurotrophic factor (BDNF) to regions of the brain affected by neurodegenerative diseases is a daunting task. Using natural products with neuroprotective properties, such as green tea polyphenols, would be a highly useful complementary approach for inexpensive long-term treatment of these diseases. In this study, we used PC12(TrkB) cells which ectopically express TrkB, a high affinity receptor for BDNF. They differentiate and induce neurite outgrowth in response to BDNF. Using this model, we show for the first time that treatment with extremely low concentrations (<0.1 μg/ml) of unfractionated green tea polyphenols (GTPP) and low concentrations (<0.5 μM) of their active ingredient, epigallocatechin-3-gallate (EGCG), potentiated the neuritogenic ability of a low concentration (2 ng/ml) of BDNF. A synergistic interaction was observed between GTPP constituents, where epigallocatechin and epicatechin, both individually lacking this activity, promoted the action of EGCG. GTPP-induced potentiation of BDNF action required the cell-surface associated 67 kDa laminin receptor (67LR) to which EGCG binds with high affinity. A cell-permeable catalase abolished GTPP/EGCG-induced potentiation of BDNF action, suggesting the possible involvement of H2O2 in the potentiation. Consistently, exogenous sublethal concentrations of H2O2, added as a bolus dose (5 μM) or more effectively through a steady-state generation (1 μM), potentiated BDNF action. Collectively, these results suggest that EGCG, dependent on 67 LR and H2O2, potentiates the neuritogenic action of BDNF. Intriguingly, this effect requires only submicromolar concentrations of EGCG. This is significant as extremely low concentrations of polyphenols are believed to reach the brain after drinking green tea.
authors: Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors: Usha
authors: U
authors: Gundimeda
authors: Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors: Thomas H
authors: TH
authors: McNeill
authors: Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors: Tiffany K
authors: TK
authors: Fan
authors: Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors: Ronald
authors: R
authors: Deng
authors: Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors: David
authors: D
authors: Rayudu
authors: Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors: Zachary
authors: Z
authors: Chen
authors: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA.
authors: Enrique
authors: E
authors: Cadenas
authors: Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: rgopalak@usc.edu.
authors: Rayudu
authors: R
authors: Gopalakrishna
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D008970:Molecular Weight; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D016877:Oxidants / Q000378:metabolism / Q000494:pharmacology; D016716:PC12 Cells; D059808:Polyphenols / Q000494:pharmacology; D051381:Rats; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D017474:Receptors, Laminin / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D013662:Tea / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D019208:Brain-Derived Neurotrophic Factor; D016877:Oxidants; D059808:Polyphenols; D017474:Receptors, Laminin; D013662:Tea; D002392:Catechin; D006861:Hydrogen Peroxide; C045651:epigallocatechin gallate; D020813:Receptor, trkB
keywords: 67-kDa laminin receptor; Brain-derived neurotrophic factor; Epigallocatechin-3-gallate; Green tea polyphenol; Hydrogen peroxide; Neuritogenesis