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

TY - JOUR

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

AU - Machado, Ana Manuel Dantas

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 - 2013/10

Y1 - 2013/10

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.

U2 - 10.1016/j.mad.2013.08.004

DO - 10.1016/j.mad.2013.08.004

M3 - Journal article

C2 - 24012633

SN - 0047-6374

VL - 134

SP - 460

EP - 466

JO - Mechanisms of Ageing and Development

JF - Mechanisms of Ageing and Development

IS - 10

ER -