title: Krebs Cycle Intermediates Protective against Oxidative Stress by Modulating the Level of Reactive Oxygen Species in Neuronal HT22 Cells.
abstract: Krebs cycle intermediates (KCIs) are reported to function as energy substrates in mitochondria and to exert antioxidants effects on the brain. The present study was designed to identify which KCIs are effective neuroprotective compounds against oxidative stress in neuronal cells. Here we found that pyruvate, oxaloacetate, and α-ketoglutarate, but not lactate, citrate, iso-citrate, succinate, fumarate, or malate, protected HT22 cells against hydrogen peroxide-mediated toxicity. These three intermediates reduced the production of hydrogen peroxide-activated reactive oxygen species, measured in terms of 2',7'-dichlorofluorescein diacetate fluorescence. In contrast, none of the KCIs-used at 1 mM-protected against cell death induced by high concentrations of glutamate-another type of oxidative stress-induced neuronal cell death. Because these protective KCIs did not have any toxic effects (at least up to 10 mM), they have potential use for therapeutic intervention against chronic neurodegenerative diseases.
authors.affiliation: Department of Anti-Aging Food Research, School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura, Hachioji 192-0982, Japan. b01131253c@edu.teu.ac.jp.
authors.forename: Kenta
authors.initials: K
authors.lastname: Sawa
authors.affiliation: Department of Anti-Aging Food Research, School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura, Hachioji 192-0982, Japan. b01130437a@edu.teu.ac.jp.
authors.forename: Takumi
authors.initials: T
authors.lastname: Uematsu
authors.affiliation: Department of Anti-Aging Food Research, School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura, Hachioji 192-0982, Japan. b0113111b5@edu.teu.ac.jp.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Korenaga
authors.affiliation: Department of Anti-Aging Food Research, School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura, Hachioji 192-0982, Japan. b01132115c@edu.teu.ac.jp.
authors.forename: Ryuya
authors.initials: R
authors.lastname: Hirasawa
authors.affiliation: Department of Anti-Aging Food Research, School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura, Hachioji 192-0982, Japan. b01130888d@edu.teu.ac.jp.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kikuchi
authors.affiliation: Department of Anti-Aging Food Research, School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura, Hachioji 192-0982, Japan. b0113245f8@edu.teu.ac.jp.
authors.forename: Kyohei
authors.initials: K
authors.lastname: Murata
authors.affiliation: Department of Anti-Aging Food Research, School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura, Hachioji 192-0982, Japan. 1099813793zj@gmail.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Anti-Aging Food Research, School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura, Hachioji 192-0982, Japan. g11160462a@edu.teu.ac.jp.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Gai
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8572, Japan. sakamoto@biol.tsukuba.ac.jp.
authors.forename: Kazuichi
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Laboratory of Nutraceuticals and Functional Foods Science, Graduate School of Marine Science and Technology, Tokyo University of Marine Science and Technology, 4-5-7 Konan, Tokyo 108-8477, Japan. tskoyama@kaiyodai.ac.jp.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Koyama
authors.affiliation: Department of Anti-Aging Food Research, School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura, Hachioji 192-0982, Japan. satotkm@stf.teu.ac.jp.
authors.forename: Takumi
authors.initials: T
authors.lastname: Satoh
keywords: alpha-ketoglutaric acid; neuron; oxaloacetic acid; pyruvic acid; reactive oxygen species