title: Attenuation of 6-hydroxydopamine (6-OHDA)-induced nuclear factor-kappaB (NF-kappaB) activation and cell death by tea extracts in neuronal cultures.
abstract: Antioxidant and anti-inflammatory therapy approaches have been in the focus of attention in the treatment of neurodegenerative Parkinson's and Alzheimer's diseases where oxidative stress has been implicated. Tea extracts have been previously reported to possess radical scavenger, iron chelating and anti-inflammatory properties in a variety of tissues. The purpose of this study was to investigate potential neuroprotective effects of tea extracts and possible signal pathway involved in a neuronal cell model of Parkinson's disease. We demonstrated highly potent antioxidant-radical scavenging activities of green tea (GT) and black tea (BT) extracts on brain mitochondrial membrane fraction, against iron (2.5 microM)-induced lipid peroxidation. Both extracts (0.6-3 microM total polyphenols) were shown to attenuate the neurotoxic action of 6-hydroxydopamine (6-OHDA)-induced neuronal death. 6-OHDA (350 and 50 microM) activated the iron dependent inflammatory redox sensitive nuclear factor-kappaB (NF-kappaB) in rat pheochromocytoma (PC12) and human neuroblastoma (NB) SH-SY5Y cells, respectively. Immunofluorescence and electromobility shift assays showed increased nuclear translocation and binding activity of NF-kappaB after exposure to 6-OHDA in NB SH-SY5Y cells, with a concomitant disappearance from the cytoplasm. Introduction of GT extract (0.6, 3 microM total polyphenols) before 6-OHDA inhibited both NF-kappaB nuclear translocation and binding activity induced by this toxin in NB SH-SY5Y cells. Neuroprotection was attributed to the potent antioxidant and iron chelating actions of the polyphenolic constituents of tea extracts, preventing nuclear translocation and activation of cell death promoting NF-kappaB. Brain penetrating property of polyphenols may make such compounds an important class of drugs for treatment of neurodegenerative diseases.
authors.affiliation: Eve Topf and USA National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research,Technion-Faculty of Medicine, Haifa, Israel
authors.forename: Yona
authors.initials: Y
authors.lastname: Levites
authors.forename: Moussa B H
authors.initials: MB
authors.lastname: Youdim
authors.forename: Gila
authors.initials: G
authors.lastname: Maor
authors.forename: Silvia
authors.initials: S
authors.lastname: Mandel
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology*; D016716:PC12 Cells; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D013662:Tea / Q000737:chemistry*; D014407:Tumor Cells, Cultured
chemical_list: D018663:Adrenergic Agents; D000975:Antioxidants; D016328:NF-kappa B; D018696:Neuroprotective Agents; D010936:Plant Extracts; D013662:Tea; D016627:Oxidopamine