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

Abstract

Cell death linked to DNA damage has been implicated in Helicobacter pylori (H. pylori) ‐ infected gastric diseases. During DNA damage, DNA repair proteins, Ku70 and Ku80, prevent cell death but severe DNA damage beyond the capacity of the DNA repair proteins triggers cell death. It has been hypothesized that the decrease in Ku70 and Ku80 may be related to cell death in H. pylori‐infected gastric epithelial cells. In this study, it was found that H. pylori induced cell death with increasing time and amounts of H. pylori added to the cells, which was determined by decreased in viable cell numbers and poly(ADP‐ribose) polymerase (PARP) cleavage. H. pylori resulted in significant decrease in both cytoplasmic and nuclear Ku protein levels as well as nuclear Ku DNA end‐binding with time and amounts of H. pylori added to the cells. H. pylori‐induced decrease in Ku proteins in cytoplasm and nucleus was in parallel with increase in ubiquitinated Ku70 and Ku80 in the whole cell extracts. H. pylori‐induced alterations in Ku expression, cell death and DNA fragmentation were inhibited by a calpain inhibitor, calpeptin and a proteasome inhibitor, lactacystin. In conclusion, loss of Ku proteins may cause the loss of defense against DNA damage and thus, underlie the mechanism of cell death in gastric epithelial cells after H. pylori infection.