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Krebs Cycle Intermediates Protective against Oxidative Stress by Modulating the Level of Reactive Oxygen Species in Neuronal HT22 Cells

1
Department of Anti-Aging Food Research, School of Bioscience and Biotechnology, Tokyo University of Technology, 1404-1 Katakura, Hachioji 192-0982, Japan
2
Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8572, Japan
3
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
*
Author to whom correspondence should be addressed.
Academic Editor: Debasis Mondal
Antioxidants 2017, 6(1), 21; https://doi.org/10.3390/antiox6010021
Received: 18 January 2017 / Revised: 20 February 2017 / Accepted: 24 February 2017 / Published: 16 March 2017
(This article belongs to the Special Issue Oxidative Stress and Cancer: The Nrf2 Enigma)
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. View Full-Text
Keywords: oxaloacetic acid; alpha-ketoglutaric acid; pyruvic acid; reactive oxygen species; neuron oxaloacetic acid; alpha-ketoglutaric acid; pyruvic acid; reactive oxygen species; neuron
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MDPI and ACS Style

Sawa, K.; Uematsu, T.; Korenaga, Y.; Hirasawa, R.; Kikuchi, M.; Murata, K.; Zhang, J.; Gai, X.; Sakamoto, K.; Koyama, T.; Satoh, T. Krebs Cycle Intermediates Protective against Oxidative Stress by Modulating the Level of Reactive Oxygen Species in Neuronal HT22 Cells. Antioxidants 2017, 6, 21. https://doi.org/10.3390/antiox6010021

AMA Style

Sawa K, Uematsu T, Korenaga Y, Hirasawa R, Kikuchi M, Murata K, Zhang J, Gai X, Sakamoto K, Koyama T, Satoh T. Krebs Cycle Intermediates Protective against Oxidative Stress by Modulating the Level of Reactive Oxygen Species in Neuronal HT22 Cells. Antioxidants. 2017; 6(1):21. https://doi.org/10.3390/antiox6010021

Chicago/Turabian Style

Sawa, Kenta, Takumi Uematsu, Yusuke Korenaga, Ryuya Hirasawa, Masatoshi Kikuchi, Kyohei Murata, Jian Zhang, Xiaoqing Gai, Kazuichi Sakamoto, Tomoyuki Koyama, and Takumi Satoh. 2017. "Krebs Cycle Intermediates Protective against Oxidative Stress by Modulating the Level of Reactive Oxygen Species in Neuronal HT22 Cells" Antioxidants 6, no. 1: 21. https://doi.org/10.3390/antiox6010021

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