A bacterial metabolite induces Nrf2-mediated anti-oxidative responses in gingival epithelial cells by activating the MAPK signaling pathway. (February 2020)

• Record Type: Journal Article
• Authors: Yokoji-Takeuchi, Mai; Takahashi, Naoki; Yamada-Hara, Miki; Sulijaya, Benso; Tsuzuno, Takahiro; Aoki-Nonaka, Yukari; Tabeta, Koichi; Kishino, Shigenobu; Ogawa, Jun; Yamazaki, Kazuhisa
• Is Part Of: Archives of oral biology. Volume 110(2020)
• Publication Date: 2020-02
• Subjects: Nrf2 nuclear erythroid-2-p45-related factor-2 -- ARE antioxidant response element -- HO-1 heme oxygenase-1 -- NQO1 NAD(P)H:quinone oxidoreductase 1 -- HYA 10- hydroxy-cis-12-octadecenoic acid -- HYB 10-hydroxyoctadacanoic acid -- HYC 10-hydroxy-trans-11-octadecenoic acid -- KetoB 10-oxo-cis-12-octadecenoic acid, 10-oxooctadecanoic acid -- KetoC 10-oxo-trans-11-octadecenoic acid -- GECs gingival epithelial cells -- ROS reactive oxygen species -- ERK extracellular signal-regulated kinase -- GPR120 G protein-coupled receptor 120 -- SFN sulforaphane -- HDAC histone deacetylase; Gingival epithelial cells -- Periodontitis -- Metabolites -- Antioxidants -- Oxidative stress; Mouth -- Periodicals; Mouth -- Diseases -- Periodicals; Dentistry -- Periodicals; Electronic journals; 617.6005
• DOI: 10.1016/j.archoralbio.2019.104602
• Languages: English
• ISSNs: 0003-9969

Abstract

Highlights: KetoC induces the expression of antioxidant-related genes in GECs. KetoC exerts a protective function against oxidative stress via GPR120-ERK-Nrf2-ARE. KetoC could be a potential therapeutic application for periodontal disease. Abstract: Objective: Oxidative stress, which is defined as an imbalance between pro-oxidant and antioxidant systems, has been implicated in the development and/or progression of several inflammatory diseases, including periodontal disease. The reactive oxygen species (ROS) are the primary inducers of oxidative stress. In the induction of cytoprotective enzymes, the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling in antioxidant systems takes a main role. Notably, 10-oxo- trans -11-octadecenoic acid (KetoC), known as a bioactive metabolite generated by intestinal microorganisms, has been reported to have beneficial effects on several biological responses. Therefore, we investigated the antioxidant effect of KetoC on gingival epithelial cells (GECs) in this present study. Methods: An SV40-T antigen-transformed human gingival epithelial cell line (Epi4) was used for experiments. The alteration of anti-oxidative stress related genes was analyzed by qPCR. The cellular ROS levels were evaluated by flow cytometry. To explore its molecular mechanisms, ARE promotor activity was analyzed by luciferase assay; the involvement of mitogen-activated protein kinase (MAPK) and G protein-coupled receptor 120 (GPR120) were evaluated by Western blotting and luciferase assay, respectively. Results: KetoC significantly increased the expression of antioxidant-related genes in GECs. The level of ROS was significantly inhibited by the pretreatment of KetoC. Extracellular signal-regulated kinase (ERK) phosphorylation by KetoC promoted both the nuclear translocation of Nrf2 and its binding to the ARE in GECs. Further, GPR120 regulated the activation of KetoC induced-Nrf2-ARE signaling. Conclusion: KetoC exerts a protective function against the oxidative stress in GECs through GPR120-dependent ERK-Nrf2-ARE signaling.