title: Nordihydroguaiaretic Acid Disrupts the Antioxidant Ability of Helicobacter pylori through the Repression of SodB Activity In Vitro.
abstract: Iron-cofactored superoxide dismutase (SodB) of Helicobacter pylori plays an indispensable role in the bacterium's colonization of the stomach. Previously, we demonstrated that FecA1, a Fe(3+)-dicitrate transporter homolog, contributes to SodB activation by supplying ferrous iron (Fe(2+)) to SodB, and fecA1-deletion mutant strains have reduced gastric mucosal-colonization ability in Mongolian gerbils, suggesting that FecA1 is a possible target for the development of a novel eradication therapy. This study aimed to identify novel FecA1-binding compounds in silico and then examined the effect of a predicted FecA1-binding compound on H. pylori SodB activity in vitro. Specifically, we demonstrated that nordihydroguaiaretic acid (NDGA) is a predicted FecA1-binding compound. NDGA reduced intracellular Fe(2+) levels in H. pylori and reduced SodB activity. Additionally, NDGA increased H2O2 sensitivity of H. pylori and increased the metronidazole (Mtz) sensitivity. The present study demonstrated that NDGA repressed SodB activity associated with the gastric mucosal-colonization via inhibition of intracellular Fe(2+) uptake by FecA1, suggesting that NDGA might be effective for the development of a novel eradication therapy.
authors.affiliation: Department of Biochemistry & Integrative Medical Biology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsugawa
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Mori
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Juntaro
authors.initials: J
authors.lastname: Matsuzaki
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Masaoka
authors.affiliation: Laboratory of Pharmaceutical & Medicinal Chemistry, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Hirayama
authors.affiliation: Laboratory of Pharmaceutical & Medicinal Chemistry, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Hideko
authors.initials: H
authors.lastname: Nagasawa
authors.affiliation: Biosciences and Informatics, Keio University, 3-14-1 Hiyoshi, Yokohama 223-8522, Japan.
authors.forename: Yasubumi
authors.initials: Y
authors.lastname: Sakakibara
authors.affiliation: Department of Biochemistry & Integrative Medical Biology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Suematsu
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Hidekazu
authors.identifier: 0000-0002-3855-3140
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000235:genetics / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D007501:Iron / Q000378:metabolism; D009637:Masoprocol / Q000008:administration & dosage*; D026901:Membrane Transport Proteins / Q000235:genetics*; D008795:Metronidazole / Q000008:administration & dosage; D011485:Protein Binding; D013270:Stomach / Q000382:microbiology / Q000473:pathology; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D008795:Metronidazole; D009637:Masoprocol; D007501:Iron; C087504:SodB protein, Bacteria; D013482:Superoxide Dismutase