Oxidative DNA Damage Response in Helicobacter pylori-Infected Mongolian Gerbils

Abstract

Helicobacter pylori (H. pylori) induced DNA damage which may be related to gastric cancer development. The DNA damage response coordinates DNA repair, cell-cycle transition, and apoptosis through activation of DNA damage response molecules. The damaged DNA is repaired through non-homologous end joining (NHEJ) or homologous recombination (HR). In the present study, we investigated the changes of HR DNA repair proteins (ataxia-telangiectasia-mutated; ATM, ATM and Rad3-related; ATR), NHEJ repair proteins (Ku70/80), cell cycle regulators (Chk1, Chk2), and apoptosis marker (p53/p-p53) were determined in H. pylori-infected Mongolian gerbils. In addition, the effect of an antioxidant N-acetylcysteine (NAC) on H. pylori-induced DNA damage response was determined to assess the involvement of oxidative stress on DNA damage of the animals infected with H. pylori. One week after intragastric inoculation with H. pylori, Mongolian gerbils were fed with basal diet with or without 3% NAC for 6 weeks. After 6 week, the expression levels of DNA repair proteins (Ku70/80, ATM, ATR), cell cycle regulators (Chk1, Chk2) and apoptosis marker (p-p53/p53) were increased in gastric mucosa of Mongolian gerbils, which was suppressed by NAC treatment. In conclusion, oxidative stress mediates H. pylori-induced DNA damage response including NHEJ and HR repairing processes, cell cycle arrest and apoptosis in gastric mucosa of Mongolian gerbils.

Helicobacter pylori Infection Mediates Transcriptional Alteration of Genes Involved in DNA Damage Response

“…Their ndings showed increased expression of the TP53 and CHEK2 genes simultaneously, indicating that the cell is headed for cell death after the cell cycle arrest due to DSB (32). Moreover, ATM gene expression has decreased in most studies on cancerous tissues (33,34), which contrasts with the present study's ndings.…”

Helicobacter pylori infection induced genome instability and gastric cancer

“…Ku protein levels are increased in H. pylori-infected gastric mucosal tissues of Mongolian gerbils (Bae et al 2013), suggesting that H. pylori enhances NHEJ pathways. In addition, Lim et al showed that H. pylori mediated activation NF-B-Cox2 axis helps to increase the expression of KU70/80 in human gastric cancer cells (Lim et al 2002).…”

Giardia Colonizes and Encysts in High-Density Foci in the Murine Small Intestine

“…Gerbils are often used in the study of both bacterial infections (73, 74) and parasitic infections (75, 76). Gerbils are readily infected by both assemblage A (WBC6) and assemblage B (GS) strains, though infection clearance is delayed with GS (40).…”

“…The Mongolian gerbil or jird ( Meriones unguiculatus ) is a less commonly used, yet promising animal model for giardiasis ( 72 ). Gerbils are often used in the study of both bacterial infections ( 73 , 74 ) and parasitic infections ( 75 , 76 ). Gerbils are readily infected by both assemblage A (WBC6) and assemblage B (GS) strains, though infection clearance is delayed with GS ( 40 ).…”