title: Helicobacter pylori-induced chronic inflammation causes telomere shortening of gastric mucosa by promoting PARP-1-mediated non-homologous end joining of DNA.
abstract: Helicobacter pylori infection leads to chronic gastritis and increased risk of gastric cancer. The mechanism involves chronic inflammation. We aimed to determine the mechanism by which H. pylori infection causes telomere shortening in inflammatory gastric mucosa. Gastric biopsy specimens were obtained from 20 patients with chronic gastritis or peptic ulcer caused by H. pylori infection. The specimens showed increased NF-κB and superoxide dismutase activities and elevated expressions of PARP-1 and γ-H2AX, all of which returned to normal levels after anti-H. pylori treatment, suggesting that oxidative DNA damage and PARP-1 overexpression might cause telomere shortening. In this report, we adopted DNA end joining assay and showed that H. pylori-infected gastric mucosa had increased alternative NHEJ (non-homologous end joining), implicating that telomere shortening was caused by inflammation-mediated overproduction of reactive oxygen species and PARP-1, leading to telomere shortening.
authors.affiliation: Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan. Electronic address: wplee@vghtpe.gov.tw.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Lee
authors.affiliation: Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medicine Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Hou
authors.affiliation: Department of Medicine Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Keng-Hsin
authors.initials: KH
authors.lastname: Lan
authors.affiliation: Department of Medicine Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chung-Pin
authors.initials: CP
authors.lastname: Li
authors.affiliation: Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yee
authors.initials: Y
authors.lastname: Chao
authors.affiliation: Department of Medicine Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Han-Chieh
authors.initials: HC
authors.lastname: Lin
authors.affiliation: Department of Medicine Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shou-Dong
authors.initials: SD
authors.lastname: Lee
mesh_terms: D000328:Adult; D002908:Chronic Disease; D004247:DNA / Q000737:chemistry; D004249:DNA Damage; D059766:DNA End-Joining Repair; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D005756:Gastritis / Q000378:metabolism; D016481:Helicobacter Infections / Q000188:drug therapy; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006657:Histones / Q000737:chemistry; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D007249:Inflammation / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D016615:Telomere / Q000737:chemistry / Q000648:ultrastructure*
chemical_list: D006657:Histones; D016328:NF-kappa B; D034741:RNA, Small Interfering; D004247:DNA; D006861:Hydrogen Peroxide; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D010100:Oxygen
keywords: Helicobacter pylori; Non-homologous end joining; PARP-1; Reactive oxygen species; Telomere