NF-κB, inducible nitric oxide synthase and apoptosis by Helicobacter pylori infection

Joo Weon Lim, Hyeyoung Kim, Kyung Hwan Kim

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73 Citations (Scopus)


Oxygen radicals are considered as an important regulator in the pathogenesis of Helicobacter pylori (H. pylori)-induced gastric ulceration and carcinogenesis. Inflammatory genes including inducible nitric oxide synthase (iNOS) may be regulated by oxidant-sensitive transcription factor, nuclear factor-κB (NF-κB). iNOS induction has been related to gastric apoptosis. We studied the role of NF-κB on iNOS expression and apoptosis in H. pylori-stimulated gastric epithelial AGS cells. AGS cells were treated with antisense oligonucleotide (AS ODN) for NF-κB subunit p50, an antioxidant enzyme catalase, an inhibitor of NF-κB activation pyrrolidine dithiocarbamate (PDTC), iNOS inhibitors NG-nitro-L-arginine-methyl ester (L-NAME) and 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT), a peroxynitrite donor SIN-1, and a nitric oxide donor NOC-18 in the presence or absence of H. pylori. H. pylori induced cytotocixity time- and dose-dependently, which occurred with induction in iNOS expression and nitrite production. SIN-1 and NOC-18 induced dose-dependent cytotoxicity in AGS cells. Catalase, PDTC, L-NAME, and AMT prevented H. pylori-induced cytotoxicity and apoptosis. It was related to their inhibition on iNOS expression and nitrite production. The cells treated with AS ODN had low levels of p50 and NF-κB and inhibited H. pylori-induced cytotoxicity, apoptosis, iNOS expression, and nitrite production. In conclusion, NF-κB plays a novel role in iNOS expression and apoptosis in H. pylori-infected gastric epithelial cells.

Original languageEnglish
Pages (from-to)355-366
Number of pages12
JournalFree Radical Biology and Medicine
Issue number3
Publication statusPublished - 2001 Aug 1

Bibliographical note

Funding Information:
This study was supported by a Science Research Center grant from Korea Science and Engineering Foundation (KOSEF) to the Nitric Oxide Radical Toxicity Research Center (NORTReC) made in the program year of 2000 (H.K.).

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)


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