Nordihydroguaiaretic acid disrupts the antioxidant ability of Helicobacter pylori through the repression of SodB activity in vitro

Hitoshi Tsugawa, Hideki Mori, Juntaro Matsuzaki, Tatsuhiro Masaoka, Tasuku Hirayama, Hideko Nagasawa, Yasubumi Sakakibara, Makoto Suematsu, Hidekazu Suzuki

Research output: Contribution to journalArticle

4 Citations (Scopus)

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<sup>3+</sup>-dicitrate transporter homolog, contributes to SodB activation by supplying ferrous iron (Fe<sup>2+</sup>) 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<sup>2+</sup> levels in H. pylori and reduced SodB activity. Additionally, NDGA increased H<inf>2</inf>O<inf>2</inf> 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<sup>2+</sup> uptake by FecA1, suggesting that NDGA might be effective for the development of a novel eradication therapy.

Original languageEnglish
Article number734548
JournalBioMed Research International
Volume2015
DOIs
Publication statusPublished - 2015

Fingerprint

Masoprocol
Helicobacter pylori
Antioxidants
Stomach
Gerbillinae
Metronidazole
Computer Simulation
Superoxide Dismutase
Bacteria
Iron
Chemical activation
In Vitro Techniques
Therapeutics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Nordihydroguaiaretic acid disrupts the antioxidant ability of Helicobacter pylori through the repression of SodB activity in vitro. / Tsugawa, Hitoshi; Mori, Hideki; Matsuzaki, Juntaro; Masaoka, Tatsuhiro; Hirayama, Tasuku; Nagasawa, Hideko; Sakakibara, Yasubumi; Suematsu, Makoto; Suzuki, Hidekazu.

In: BioMed Research International, Vol. 2015, 734548, 2015.

Research output: Contribution to journalArticle

@article{a27b92ba8617411c9f9066c93fb2331d,
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 Fe3+-dicitrate transporter homolog, contributes to SodB activation by supplying ferrous iron (Fe2+) 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 Fe2+ 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 Fe2+ uptake by FecA1, suggesting that NDGA might be effective for the development of a novel eradication therapy.",
author = "Hitoshi Tsugawa and Hideki Mori and Juntaro Matsuzaki and Tatsuhiro Masaoka and Tasuku Hirayama and Hideko Nagasawa and Yasubumi Sakakibara and Makoto Suematsu and Hidekazu Suzuki",
year = "2015",
doi = "10.1155/2015/734548",
language = "English",
volume = "2015",
journal = "BioMed Research International",
issn = "2314-6133",
publisher = "Hindawi Publishing Corporation",

}

TY - JOUR

T1 - Nordihydroguaiaretic acid disrupts the antioxidant ability of Helicobacter pylori through the repression of SodB activity in vitro

AU - Tsugawa, Hitoshi

AU - Mori, Hideki

AU - Matsuzaki, Juntaro

AU - Masaoka, Tatsuhiro

AU - Hirayama, Tasuku

AU - Nagasawa, Hideko

AU - Sakakibara, Yasubumi

AU - Suematsu, Makoto

AU - Suzuki, Hidekazu

PY - 2015

Y1 - 2015

N2 - 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 Fe3+-dicitrate transporter homolog, contributes to SodB activation by supplying ferrous iron (Fe2+) 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 Fe2+ 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 Fe2+ uptake by FecA1, suggesting that NDGA might be effective for the development of a novel eradication therapy.

AB - 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 Fe3+-dicitrate transporter homolog, contributes to SodB activation by supplying ferrous iron (Fe2+) 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 Fe2+ 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 Fe2+ uptake by FecA1, suggesting that NDGA might be effective for the development of a novel eradication therapy.

UR - http://www.scopus.com/inward/record.url?scp=84928472963&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84928472963&partnerID=8YFLogxK

U2 - 10.1155/2015/734548

DO - 10.1155/2015/734548

M3 - Article

VL - 2015

JO - BioMed Research International

JF - BioMed Research International

SN - 2314-6133

M1 - 734548

ER -