PMID- 24508265 OWN - NLM STAT- MEDLINE DCOM- 20140502 LR - 20140303 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 445 IP - 1 DP - 2014 Feb 28 TI - Green tea catechins potentiate the neuritogenic action of brain-derived neurotrophic factor: role of 67-kDa laminin receptor and hydrogen peroxide. PG - 218-24 LID - S0006-291X(14)00209-5 [pii] LID - 10.1016/j.bbrc.2014.01.166 [doi] AB - 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 mug/ml) of unfractionated green tea polyphenols (GTPP) and low concentrations (<0.5 muM) 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 muM) or more effectively through a steady-state generation (1 muM), 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. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Gundimeda, Usha AU - Gundimeda U AD - Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. FAU - McNeill, Thomas H AU - McNeill TH AD - Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. FAU - Fan, Tiffany K AU - Fan TK AD - Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. FAU - Deng, Ronald AU - Deng R AD - Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. FAU - Rayudu, David AU - Rayudu D AD - Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. FAU - Chen, Zachary AU - Chen Z AD - Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. FAU - Cadenas, Enrique AU - Cadenas E AD - Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA. FAU - Gopalakrishna, Rayudu AU - Gopalakrishna R AD - Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. Electronic address: rgopalak@usc.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140204 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Antioxidants) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Oxidants) RN - 0 (Polyphenols) RN - 0 (Receptors, Laminin) RN - 0 (Tea) RN - 8R1V1STN48 (Catechin) RN - BBX060AN9V (Hydrogen Peroxide) RN - BQM438CTEL (epigallocatechin gallate) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Antioxidants/pharmacology MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Catechin/analogs & derivatives/*pharmacology MH - Dose-Response Relationship, Drug MH - Drug Synergism MH - Hydrogen Peroxide/metabolism/pharmacology MH - Molecular Weight MH - Neurites/*drug effects/physiology MH - Oxidants/metabolism/pharmacology MH - PC12 Cells MH - Polyphenols/pharmacology MH - Rats MH - Receptor, trkB/genetics/metabolism MH - Receptors, Laminin/chemistry/metabolism/physiology MH - Tea/*chemistry OTO - NOTNLM OT - 67-kDa laminin receptor OT - Brain-derived neurotrophic factor OT - Epigallocatechin-3-gallate OT - Green tea polyphenol OT - Hydrogen peroxide OT - Neuritogenesis EDAT- 2014/02/11 06:00 MHDA- 2014/05/03 06:00 CRDT- 2014/02/11 06:00 PHST- 2014/01/20 00:00 [received] PHST- 2014/01/28 00:00 [accepted] PHST- 2014/02/11 06:00 [entrez] PHST- 2014/02/11 06:00 [pubmed] PHST- 2014/05/03 06:00 [medline] AID - S0006-291X(14)00209-5 [pii] AID - 10.1016/j.bbrc.2014.01.166 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2014 Feb 28;445(1):218-24. doi: 10.1016/j.bbrc.2014.01.166. Epub 2014 Feb 4.