title: 10-Oxo-trans-11-octadecenoic acid generated from linoleic acid by a gut lactic acid bacterium Lactobacillus plantarum is cytoprotective against oxidative stress.
abstract: Oxidative stress is a well-known cause of multiple diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a central role in cellular antioxidative responses. In this study, we investigated the effects of novel fatty acid metabolite derivatives of linoleic acid generated by the gut lactic acid bacteria Lactobacillus plantarum on the Nrf2-ARE pathway. 10-Oxo-trans-11-octadecenoic acid (KetoC) protected HepG2 cells from cytotoxicity induced by hydrogen peroxide. KetoC also significantly increased cellular Nrf2 protein levels, ARE-dependent transcription, and the gene expression of antioxidative enzymes such as heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and
  quinone oxidoreductase 1 (NQO1) in HepG2 cells. Additionally, a single oral dose administration of KetoC also increased antioxidative gene expression and protein levels of Nrf2 and HO-1 in mouse organs. Since other fatty acid metabolites and linoleic acid did not affect cellular antioxidative responses, the cytoprotective effect of KetoC may be because of its α,β-unsaturated carbonyl moiety. Collectively, our data suggested that KetoC activated the Nrf2-ARE pathway to enhance cellular antioxidative responses in vitro and in vivo, which further suggests that KetoC may prevent multiple diseases induced by oxidative stress.
authors.affiliation: Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Furumoto
authors.affiliation: Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Tharnath
authors.initials: T
authors.lastname: Nanthirudjanar
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29, Simoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kume
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29, Simoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Izumi
authors.affiliation: Laboratory of Industrial Microbiology, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Si-Bum
authors.initials: SB
authors.lastname: Park
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Nahoko
authors.initials: N
authors.lastname: Kitamura
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Kishino
authors.affiliation: Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Ogawa
authors.affiliation: Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan; Faculty of Rehabilitation, Shijonawategakuen University, 5-11-10, Hojo, Daitou-shi, Osaka 574-0011, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirata
authors.affiliation: Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan. Electronic address: sugawara@kais.kyoto-u.ac.jp.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sugawara
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology*; D056945:Hep G2 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D019344:Lactic Acid / Q000378:metabolism*; D048191:Lactiplantibacillus plantarum / Q000378:metabolism*; D019787:Linoleic Acid / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009829:Oleic Acids / Q000737:chemistry / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*
chemical_list: D009829:Oleic Acids; D019344:Lactic Acid; D019787:Linoleic Acid; D006861:Hydrogen Peroxide; C050413:11-octadecenoic acid
keywords: Gut microorganism; Hydroxy and oxo fatty acids; Lactic acid bacterium; Nrf2-ARE pathway; Oxidative stress; Polyunsaturated fatty acids