scholarly journals Loss of DNA Repair Protein and Cell Death in Helicobacter pylori ‐Infected Gastric Epithelial Cells

2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Hyeyoung Kim ◽  
Sang Hui Chu ◽  
Joo Weon Lim
Keyword(s):  
Cell Death ◽  
Dna Repair ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Gastric Epithelial Cells ◽  
Repair Protein ◽  
Dna Repair Protein

scholarly journals Helicobacter pylori Induces Gastric Epithelial Cell Apoptosis in Association with Increased Fas Receptor Expression

1999 ◽  
Vol 67 (8) ◽  
pp. 4237-4242 ◽  
Author(s):  
Nicola L. Jones ◽  
Andrew S. Day ◽  
Hilary A. Jennings ◽  
Philip M. Sherman
Keyword(s):  
Cell Death ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Receptor Expression ◽  
Gastric Epithelial Cells ◽  
Ags Cells ◽  
Fas Receptor ◽  
Epithelial Cell Apoptosis ◽  
H Pylori

ABSTRACT The mechanisms involved in mediating the enhanced gastric epithelial cell apoptosis observed during infection withHelicobacter pylori in vivo are unknown. To determine whether H. pylori directly induces apoptosis of gastric epithelial cells in vitro and to define the role of the Fas-Fas ligand signal transduction cascade, human gastric epithelial cells were infected with H. pylori for up to 72 h under microaerophilic conditions. As assessed by both transmission electron microscopy and fluorescence microscopy, incubation with acagA-positive, cagE-positive, VacA-positive clinical H. pylori isolate stimulated an increase in apoptosis compared to the apoptosis of untreated AGS cells (16.0% ± 2.8% versus 5.9% ± 1.4%, P < 0.05) after 72 h. In contrast, apoptosis was not detected following infection withcagA-negative, cagE-negative, VacA-negative clinical isolates or a Campylobacter jejuni strain. In addition to stimulating apoptosis, infection with H. pylorienhanced Fas receptor expression in AGS cells to a degree comparable to that of treatment with a positive control, gamma interferon (12.5 ng/ml) (148% ± 24% and 167% ± 24% of control, respectively). The enhanced Fas receptor expression was associated with increased sensitivity to Fas-mediated cell death. Ligation of the Fas receptor with an agonistic monoclonal antibody resulted in an increase in apoptosis compared to the apoptosis of cells infected with the bacterium alone (38.5% ± 7.1% versus 16.0% ± 2.8%,P < 0.05). Incubation with neutralizing anti-Fas antibody did not prevent apoptosis of H. pylori-infected cells. Taken together, these findings demonstrate that the gastric pathogen H. pylori stimulates apoptosis of gastric epithelial cells in vitro in association with the enhanced expression of the Fas receptor. These data indicate a role for Fas-mediated signaling in the programmed cell death that occurs in response toH. pylori infection.

Dual DNA and DNA repair protein damage by acrolein in colon epithelial cells

2021 ◽  
Vol 350 ◽  
pp. S233
Author(s):  
T. Cruz ◽  
K.A. Hurley ◽  
J. Zgraggen ◽  
S. Diedrich ◽  
S.J. Sturla
Keyword(s):  
Dna Repair ◽  
Epithelial Cells ◽  
Protein Damage ◽  
Repair Protein ◽  
Dna Repair Protein

scholarly journals Helicobacter pylori Infection Induces Oxidative Stress and Programmed Cell Death in Human Gastric Epithelial Cells

2007 ◽  
Vol 75 (8) ◽  
pp. 4030-4039 ◽  
Author(s):  
Song-Ze Ding ◽  
Yutaka Minohara ◽  
Xue Jun Fan ◽  
Jide Wang ◽  
Victor E. Reyes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Cell Death ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Dna Fragmentation ◽  
Inflammatory Cytokines ◽  
Ros Generation ◽  
Gastric Epithelial Cells ◽  
H Pylori

ABSTRACT Helicobacter pylori infection is associated with altered gastric epithelial cell turnover. To evaluate the role of oxidative stress in cell death, gastric epithelial cells were exposed to various strains of H. pylori, inflammatory cytokines, and hydrogen peroxide in the absence or presence of antioxidant agents. Increased intracellular reactive oxygen species (ROS) were detected using a redox-sensitive fluorescent dye, a cytochrome c reduction assay, and measurements of glutathione. Apoptosis was evaluated by detecting DNA fragmentation and caspase activation. Infection with H. pylori or exposure of epithelial cells to hydrogen peroxide resulted in apoptosis and a dose-dependent increase in ROS generation that was enhanced by pretreatment with inflammatory cytokines. Basal levels of ROS were greater in epithelial cells isolated from gastric mucosal biopsy specimens from H. pylori-infected subjects than in cells from uninfected individuals. H. pylori strains bearing the cag pathogenicity island (PAI) induced higher levels of intracellular oxygen metabolites than isogenic cag PAI-deficient mutants. H. pylori infection and hydrogen peroxide exposure resulted in similar patterns of caspase 3 and 8 activation. Antioxidants inhibited both ROS generation and DNA fragmentation by H. pylori. These results indicate that bacterial factors and the host inflammatory response confer oxidative stress to the gastric epithelium during H. pylori infection that may lead to apoptosis.

scholarly journals Inhibition of Karyopherin-α2 Augments Radiation-Induced Cell Death by Perturbing BRCA1-Mediated DNA Repair

2019 ◽  
Vol 20 (11) ◽  
pp. 2843 ◽  
Author(s):  
Kyung-Hee Song ◽  
Seung-Youn Jung ◽  
Jeong-In Park ◽  
Jiyeon Ahn ◽  
Jong Kuk Park ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Dna Repair ◽  
Apoptotic Cell ◽  
Nucleocytoplasmic Transport ◽  
Repair Protein ◽  
Damage Response ◽  
Dna Repair Protein ◽  
Radiation Induced ◽  
Early Local Recurrence

Ionizing radiation (IR) has been widely used in the treatment of cancer. Radiation-induced DNA damage triggers the DNA damage response (DDR), which can confer radioresistance and early local recurrence by activating DNA repair pathways. Since karyopherin-α2 (KPNA2), playing an important role in nucleocytoplasmic transport, was significantly increased by IR in our previous study, we aimed to determine the function of KPNA2 with regard to DDR. Exposure to radiation upregulated KPNA2 expression in human colorectal cancer HT29 and HCT116 cells and breast carcinoma MDA-MB-231 cells together with the increased expression of DNA repair protein BRCA1. The knockdown of KPNA2 effectively increased apoptotic cell death via inhibition of BRCA1 nuclear import following IR. Therefore, we propose that KPNA2 is a potential target for overcoming radioresistance via interruption to DDR.

scholarly journals Helicobacter pylori VacA Induces Programmed Necrosis in Gastric Epithelial Cells

2011 ◽  
Vol 79 (7) ◽  
pp. 2535-2543 ◽  
Author(s):  
Jana N. Radin ◽  
Christian González-Rivera ◽  
Susan E. Ivie ◽  
Mark S. McClain ◽  
Timothy L. Cover
Keyword(s):  
Gastric Cancer ◽  
Cell Death ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Human Stomach ◽  
Gastric Epithelial Cells ◽  
Wild Type ◽  
Programmed Necrosis ◽  
Content Type ◽  
H Pylori

ABSTRACTHelicobacter pyloriis a Gram-negative bacterium that colonizes the human stomach and contributes to the development of peptic ulcer disease and gastric cancer. The secreted pore-forming toxin VacA is one of the major virulence factors ofH. pylori. In the current study, we show that AZ-521 human gastric epithelial cells are highly susceptible to VacA-induced cell death. Wild-type VacA causes death of these cells, whereas mutant VacA proteins defective in membrane channel formation do not. Incubation of AZ-521 cells with wild-type VacA results in cell swelling, poly(ADP-ribose) polymerase (PARP) activation, decreased intracellular ATP concentration, and lactate dehydrogenase (LDH) release. VacA-induced death of these cells is a caspase-independent process that results in cellular release of histone-binding protein high mobility group box 1 (HMGB1), a proinflammatory protein. These features are consistent with the occurrence of cell death through a programmed necrosis pathway and suggest that VacA can be included among the growing number of bacterial pore-forming toxins that induce cell death through programmed necrosis. We propose that VacA augmentsH. pylori-induced mucosal inflammation in the human stomach by causing programmed necrosis of gastric epithelial cells and subsequent release of proinflammatory proteins and may thereby contribute to the pathogenesis of gastric cancer and peptic ulceration.

scholarly journals Role of Connexin 43 in Helicobacter pylori VacA-Induced Cell Death

2013 ◽  
Vol 82 (1) ◽  
pp. 423-432 ◽  
Author(s):  
Jana N. Radin ◽  
Christian González-Rivera ◽  
Arwen E. Frick-Cheng ◽  
Jinsong Sheng ◽  
Jennifer A. Gaddy ◽  
...  
Keyword(s):  
Cell Death ◽  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Host Cell ◽  
Connexin 43 ◽  
Gene Trap ◽  
Gastric Epithelial Cells ◽  
Content Type ◽  
Increased Risk ◽  
Junction Protein

ABSTRACTHelicobacter pyloricolonizes the human stomach and confers an increased risk for the development of peptic ulceration, noncardia gastric adenocarcinoma, and gastric lymphoma. A secretedH. pyloritoxin, VacA, can cause multiple alterations in gastric epithelial cells, including cell death. In this study, we sought to identify host cell factors that are required for VacA-induced cell death. To do this, we analyzed gene trap and short hairpin RNA (shRNA) libraries in AZ-521 human gastric epithelial cells and selected for VacA-resistant clones. Among the VacA-resistant clones, we identified multiple gene trap library clones and an shRNA library clone with disrupted expression of connexin 43 (Cx43) (also known as gap junction protein alpha 1 [GJA1]). Further experiments withCx43-specific shRNAs confirmed that a reduction inCx43expression results in resistance to VacA-induced cell death. Immunofluorescence microscopy experiments indicated that VacA did not colocalize with Cx43. We detected production of the Cx43 protein in AZ-521 cells but not in AGS, HeLa, or RK-13 cells, and correspondingly, AZ-521 cells were the most susceptible to VacA-induced cell death. When Cx43 was expressed in HeLa cells, the cells became more susceptible to VacA. These results indicate that Cx43 is a host cell constituent that contributes to VacA-induced cell death and that variation among cell types in susceptibility to VacA-induced cell death is attributable at least in part to cell type-specific differences in Cx43 production.

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