title: Phytochemicals prevent mitochondrial membrane permeabilization and protect SH-SY5Y cells against apoptosis induced by PK11195, a ligand for outer membrane translocator protein.
abstract: Epidemiological studies present the beneficial effects of dietary habits on prevention of aging-associated decline of brain function. Phytochemicals, the second metabolites of food, protect neuronal cells from cell death in cellular models of neurodegenerative disorders, and the neuroprotective activity has been ascribed to the anti-oxidant and anti-inflammatory functions. In this paper, the cellular mechanism of neuroprotection by phytochemicals was investigated, using the cellular model of mitochondrial apoptosis induced by PK11195, a ligand of outer membrane translocator protein, in SH-SY5Y cells. PK11195 induced mitochondrial membrane permeabilization with rapid transit production of superoxide (superoxide flashes) and calcium release from mitochondria, and activated apoptosis signal pathway. Study on the structure-activity relationship of astaxanthin, ferulic acid derivatives, and sesame lignans revealed that these phytochemicals inhibited mitochondrial membrane permeabilization and protected cells from apoptosis. Ferulic acid derivatives and sesame lignans inhibited or enhanced the mitochondrial pore formation and cell death by PK11195 according to their amphiphilic properties, not directly depending on the antioxidant activity. Regulation of pore formation at mitochondrial membrane is discussed as a novel mechanism behind neuroprotective activity of phytochemicals in aging and age-associated neurodegenerative disorders, and also behind dual functions of phytochemicals in neuronal and cancer cells.
authors.affiliation: Department of Health and Nutrition, Faculty of Psychological and Physical Science, Aichi Gakuin University, 12 Araike, Iwasaki-cho, Nisshin, Aichi, 320-0195, Japan.
authors.forename: Yuqiu
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Health and Nutrition, Faculty of Psychological and Physical Science, Aichi Gakuin University, 12 Araike, Iwasaki-cho, Nisshin, Aichi, 320-0195, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Shamoto-Nagai
authors.affiliation: Department of Health and Nutrition, Faculty of Psychological and Physical Science, Aichi Gakuin University, 12 Araike, Iwasaki-cho, Nisshin, Aichi, 320-0195, Japan.
authors.forename: Wakako
authors.initials: W
authors.lastname: Maruyama
authors.affiliation: Department of Health and Nutrition, Faculty of Psychological and Physical Science, Aichi Gakuin University, 12 Araike, Iwasaki-cho, Nisshin, Aichi, 320-0195, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Osawa
authors.affiliation: Department of Health and Nutrition, Faculty of Psychological and Physical Science, Aichi Gakuin University, 12 Araike, Iwasaki-cho, Nisshin, Aichi, 320-0195, Japan. mnaoi@dpc.agu.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Naoi
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003373:Coumaric Acids / Q000737:chemistry / Q000494:pharmacology; D004149:Dioxoles / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007546:Isoquinolines / Q000633:toxicity*; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D064209:Phytochemicals / Q000737:chemistry / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D024341:Xanthophylls / Q000737:chemistry / Q000494:pharmacology
chemical_list: C000595707:BCL2 protein, human; D002413:Cations, Divalent; D003373:Coumaric Acids; D004149:Dioxoles; D007546:Isoquinolines; D017705:Lignans; D033681:Mitochondrial Membrane Transport Proteins; D018696:Neuroprotective Agents; D064209:Phytochemicals; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D024341:Xanthophylls; C005948:astaxanthine; C004999:ferulic acid; C054125:sesamin; D010100:Oxygen; D002118:Calcium; C037850:PK 11195
keywords: Apoptosis; Calcium; Neuroprotection; PK11195; Phytochemicals; Superoxide flash