title: Polyphenols from green tea prevent antineuritogenic action of Nogo-A via 67-kDa laminin receptor and hydrogen peroxide.
abstract: Axonal regeneration after injury to the CNS is hampered by myelin-derived inhibitors, such as Nogo-A. Natural products, such as green tea, which are neuroprotective and safe for long-term therapy, would complement ongoing various pharmacological approaches. In this study, using nerve growth factor-differentiated neuronal-like Neuroscreen-1 cells, we show that extremely low concentrations of unfractionated green tea polyphenol mixture (GTPP) and its active ingredient, epigallocatechin-3-gallate (EGCG), prevent both the neurite outgrowth-inhibiting activity and growth cone-collapsing activity of Nogo-66 (C-terminal domain of Nogo-A). Furthermore, a synergistic interaction was observed among GTPP constituents. This preventive effect was dependent on 67-kDa laminin receptor (67LR) to which EGCG binds with high affinity. The antioxidants N-acetylcysteine and cell-permeable catalase abolished this preventive effect of GTPP and EGCG, suggesting the involvement of sublethal levels of H2 O2 in this process. Accordingly, exogenous sublethal concentrations of H2 O2 , added as a bolus dose (5 μM) or more effectively through a steady-state generation (1-2 μM), mimicked GTPP in counteracting the action of Nogo-66. Exogenous H2 O2 mediated this action by bypassing the requirement of 67LR. Taken together, these results show for the first time that GTPP and EGCG, acting through 67LR and elevating intracellular sublethal levels of H2 O2 , inhibit the antineuritogenic action of Nogo-A. Currently, several agents are being evaluated for overcoming axonal growth inhibitors to promote functional recovery after stroke and spinal cord injury. Epigallocatechin-3-gallate (EGCG), present in green tea polyphenol mixture (GTPP), prevents antineuritogenic activity of Nogo-A, a myelin-derived axonal growth inhibitor. The preventive action of EGCG involves the cell-surface-associated 67-kDa laminin receptor and H2 O2 . GTPP may complement ongoing efforts to treat neuronal injuries.>
authors.affiliation: Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
authors.forename: Usha
authors.initials: U
authors.lastname: Gundimeda
authors.forename: Thomas H
authors.initials: TH
authors.lastname: McNeill
authors.forename: Barsegh A
authors.initials: BA
authors.lastname: Barseghian
authors.forename: William S
authors.initials: WS
authors.lastname: Tzeng
authors.forename: David V
authors.initials: DV
authors.lastname: Rayudu
authors.forename: Enrique
authors.initials: E
authors.lastname: Cadenas
authors.forename: Rayudu
authors.initials: R
authors.lastname: Gopalakrishna
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D020439:Growth Cones / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D051379:Mice; D009185:Myelin Proteins / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects*; D000070798:Nogo Proteins; D016877:Oxidants / Q000494:pharmacology*; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology*; D011554:Pseudopodia / Q000187:drug effects; D017474:Receptors, Laminin / Q000187:drug effects*; D013662:Tea / Q000737:chemistry*
chemical_list: D009185:Myelin Proteins; D000070798:Nogo Proteins; D016877:Oxidants; D059808:Polyphenols; D017474:Receptors, Laminin; C000603201:Rtn4 protein, mouse; D013662:Tea; D006861:Hydrogen Peroxide
keywords: 67-kDa laminin receptor; Nogo-A; epigallocatechin-3-gallate; green tea polyphenols; hydrogen peroxide; neurite outgrowth