Helicobacter pylori infection affects mitochondrial function and DNA repair, thus, mediating genetic instability in gastric cells

Ana Manuel Machado, Claus Desler, Sisse Boggild, Jesper A.B. Strickertsson, Lennart Friis-Hansen, Ceu Figueiredo, Raquel Seruca, Lene Juel Rasmussen

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    Helicobacter pylori infection is an important factor for the development of atrophic gastritis and gastric carcinogenesis. However, the mechanisms explaining the effects of H. pylori infection are not fully elucidated. H. pylori infection is known to induce genetic instability in both nuclear and mitochondrial DNA of gastric epithelial cells. The mutagenic effect of H. pylori infection on nuclear DNA is known to be a consequence, in part, of a down-regulation of expression and activity of major DNA repair pathways. In this study, we demonstrate that H. pylori infection of gastric adenocarcinoma cells causes mtDNA mutations and a decrease of mtDNA content. Consequently, we show a decrease of respiration coupled ATP turnover and respiratory capacity and accordingly a lower level and activity of complex I of the electron transport chain. We wanted to investigate if the increased mutational load in the mitochondrial genome was caused by down-regulation of mitochondrial DNA repair pathways. We lowered the expression of APE-1 and YB-1, which are believed to be involved in mitochondrial base excision repair and mismatch repair. Our results suggest that both APE-1 and YB-1 are involved in mtDNA repair during H. pylori infection, furthermore, the results demonstrate that multiple DNA repair activities are involved in protecting mtDNA during infection.
    OriginalsprogEngelsk
    TidsskriftMechanisms of Ageing and Development
    Vol/bind134
    Udgave nummer10
    Sider (fra-til)460-466
    ISSN0047-6374
    DOI
    StatusUdgivet - 2013

    Emneord

    • H. pylori
    • Mitochondria
    • Gastric cancer
    • DNA repair
    • Genetic instability

    Citer dette

    Machado, A. M., Desler, C., Boggild, S., Strickertsson, J. A. B., Friis-Hansen, L., Figueiredo, C., ... Rasmussen, L. J. (2013). Helicobacter pylori infection affects mitochondrial function and DNA repair, thus, mediating genetic instability in gastric cells. Mechanisms of Ageing and Development, 134(10), 460-466. https://doi.org/10.1016/j.mad.2013.08.004
    Machado, Ana Manuel ; Desler, Claus ; Boggild, Sisse ; Strickertsson, Jesper A.B. ; Friis-Hansen, Lennart ; Figueiredo, Ceu ; Seruca, Raquel ; Rasmussen, Lene Juel. / Helicobacter pylori infection affects mitochondrial function and DNA repair, thus, mediating genetic instability in gastric cells. I: Mechanisms of Ageing and Development. 2013 ; Bind 134, Nr. 10. s. 460-466.
    @article{267ef4112ea2485d8f51f4c522206db2,
    title = "Helicobacter pylori infection affects mitochondrial function and DNA repair, thus, mediating genetic instability in gastric cells",
    abstract = "Helicobacter pylori infection is an important factor for the development of atrophic gastritis and gastric carcinogenesis. However, the mechanisms explaining the effects of H. pylori infection are not fully elucidated. H. pylori infection is known to induce genetic instability in both nuclear and mitochondrial DNA of gastric epithelial cells. The mutagenic effect of H. pylori infection on nuclear DNA is known to be a consequence, in part, of a down-regulation of expression and activity of major DNA repair pathways. In this study, we demonstrate that H. pylori infection of gastric adenocarcinoma cells causes mtDNA mutations and a decrease of mtDNA content. Consequently, we show a decrease of respiration coupled ATP turnover and respiratory capacity and accordingly a lower level and activity of complex I of the electron transport chain. We wanted to investigate if the increased mutational load in the mitochondrial genome was caused by down-regulation of mitochondrial DNA repair pathways. We lowered the expression of APE-1 and YB-1, which are believed to be involved in mitochondrial base excision repair and mismatch repair. Our results suggest that both APE-1 and YB-1 are involved in mtDNA repair during H. pylori infection, furthermore, the results demonstrate that multiple DNA repair activities are involved in protecting mtDNA during infection.",
    keywords = "H. pylori, Mitochondria, Gastric cancer, DNA repair, Genetic instability, H. pylori, Mitochondria, Gastric cancer, DNA repair, Genetic instability",
    author = "Machado, {Ana Manuel} and Claus Desler and Sisse Boggild and Strickertsson, {Jesper A.B.} and Lennart Friis-Hansen and Ceu Figueiredo and Raquel Seruca and Rasmussen, {Lene Juel}",
    year = "2013",
    doi = "10.1016/j.mad.2013.08.004",
    language = "English",
    volume = "134",
    pages = "460--466",
    journal = "Mechanisms of Ageing and Development",
    issn = "0047-6374",
    publisher = "Elsevier Ireland Ltd",
    number = "10",

    }

    Machado, AM, Desler, C, Boggild, S, Strickertsson, JAB, Friis-Hansen, L, Figueiredo, C, Seruca, R & Rasmussen, LJ 2013, 'Helicobacter pylori infection affects mitochondrial function and DNA repair, thus, mediating genetic instability in gastric cells', Mechanisms of Ageing and Development, bind 134, nr. 10, s. 460-466. https://doi.org/10.1016/j.mad.2013.08.004

    Helicobacter pylori infection affects mitochondrial function and DNA repair, thus, mediating genetic instability in gastric cells. / Machado, Ana Manuel; Desler, Claus; Boggild, Sisse; Strickertsson, Jesper A.B.; Friis-Hansen, Lennart; Figueiredo, Ceu; Seruca, Raquel; Rasmussen, Lene Juel.

    I: Mechanisms of Ageing and Development, Bind 134, Nr. 10, 2013, s. 460-466.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - Helicobacter pylori infection affects mitochondrial function and DNA repair, thus, mediating genetic instability in gastric cells

    AU - Machado, Ana Manuel

    AU - Desler, Claus

    AU - Boggild, Sisse

    AU - Strickertsson, Jesper A.B.

    AU - Friis-Hansen, Lennart

    AU - Figueiredo, Ceu

    AU - Seruca, Raquel

    AU - Rasmussen, Lene Juel

    PY - 2013

    Y1 - 2013

    N2 - Helicobacter pylori infection is an important factor for the development of atrophic gastritis and gastric carcinogenesis. However, the mechanisms explaining the effects of H. pylori infection are not fully elucidated. H. pylori infection is known to induce genetic instability in both nuclear and mitochondrial DNA of gastric epithelial cells. The mutagenic effect of H. pylori infection on nuclear DNA is known to be a consequence, in part, of a down-regulation of expression and activity of major DNA repair pathways. In this study, we demonstrate that H. pylori infection of gastric adenocarcinoma cells causes mtDNA mutations and a decrease of mtDNA content. Consequently, we show a decrease of respiration coupled ATP turnover and respiratory capacity and accordingly a lower level and activity of complex I of the electron transport chain. We wanted to investigate if the increased mutational load in the mitochondrial genome was caused by down-regulation of mitochondrial DNA repair pathways. We lowered the expression of APE-1 and YB-1, which are believed to be involved in mitochondrial base excision repair and mismatch repair. Our results suggest that both APE-1 and YB-1 are involved in mtDNA repair during H. pylori infection, furthermore, the results demonstrate that multiple DNA repair activities are involved in protecting mtDNA during infection.

    AB - Helicobacter pylori infection is an important factor for the development of atrophic gastritis and gastric carcinogenesis. However, the mechanisms explaining the effects of H. pylori infection are not fully elucidated. H. pylori infection is known to induce genetic instability in both nuclear and mitochondrial DNA of gastric epithelial cells. The mutagenic effect of H. pylori infection on nuclear DNA is known to be a consequence, in part, of a down-regulation of expression and activity of major DNA repair pathways. In this study, we demonstrate that H. pylori infection of gastric adenocarcinoma cells causes mtDNA mutations and a decrease of mtDNA content. Consequently, we show a decrease of respiration coupled ATP turnover and respiratory capacity and accordingly a lower level and activity of complex I of the electron transport chain. We wanted to investigate if the increased mutational load in the mitochondrial genome was caused by down-regulation of mitochondrial DNA repair pathways. We lowered the expression of APE-1 and YB-1, which are believed to be involved in mitochondrial base excision repair and mismatch repair. Our results suggest that both APE-1 and YB-1 are involved in mtDNA repair during H. pylori infection, furthermore, the results demonstrate that multiple DNA repair activities are involved in protecting mtDNA during infection.

    KW - H. pylori

    KW - Mitochondria

    KW - Gastric cancer

    KW - DNA repair

    KW - Genetic instability

    KW - H. pylori

    KW - Mitochondria

    KW - Gastric cancer

    KW - DNA repair

    KW - Genetic instability

    U2 - 10.1016/j.mad.2013.08.004

    DO - 10.1016/j.mad.2013.08.004

    M3 - Journal article

    VL - 134

    SP - 460

    EP - 466

    JO - Mechanisms of Ageing and Development

    JF - Mechanisms of Ageing and Development

    SN - 0047-6374

    IS - 10

    ER -