Cited by 74Helicobacter pylori-related gastroenterology studiesNF-κB Signaling PathwaysInflammatory mediators and NSAID effects

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

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Lim, Joo Weon, Kim, Hyeyoung, Kim, Kyung Hwan·2001·Free Radical Biology and Medicine

Abstract

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-kappaB (NF-kappaB). iNOS induction has been related to gastric apoptosis. We studied the role of NF-kappaB on iNOS expression and apoptosis in H. pylori-stimulated gastric epithelial AGS cells. AGS cells were treated with antisense oligonucleotide (AS ODN) for NF-kappaB subunit p50, an antioxidant enzyme catalase, an inhibitor of NF-kappaB activation pyrrolidine dithiocarbamate (PDTC), iNOS inhibitors N(G)-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-kappaB and inhibited H. pylori-induced cytotoxicity, apoptosis, iNOS expression, and nitrite production. In conclusion, NF-kappaB plays a novel role in iNOS expression and apoptosis in H. pylori-infected gastric epithelial cells.

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Crossref · 10.1016/s0891-5849(01)00592-5

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  • Chronic inflammation, including inflammatory bowel disease and Helicobacter pylori-induced gastritis, induces iNOS and generates large quantities of NO, forming nitrosating and oxidant species such as N2O3 and peroxynitrite, which might cause mutagenesis through deamination, nitration of DNA, or inhibition of the DNA repair system.

    “However, chronic inflammation, including inflammatory bowel disease and Helicobacter pylori-induced gastritis induce inducible NOS (iNOS) and generate large quantities of NO [22,146,147], forming nitrosating and oxidant species such as N2O3 and peroxynitrite, which might cause mutagenesis through deamination, nitration of DNA, or inhibition of the DNA repair system [148,149].”

    From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [146]

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Authors
Lim, J. W., Kim, H., & Kim, K. H.
Affiliations
Yonsei University (KR)
Corresponding author
Kim, Hyeyoung
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2001-08
Volume
31
Issue
3
Pages
355-366
ISSN
0891-5849 (ISSN-L)
OpenAlex
W1969957972
Cited by
74
References
77
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2022: 1 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 7 · 2012: 3
FWCI
5.87
Type
journal article
Language
en
Open access
Locations
  • Free Radical Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
Topics
  • Health Sciences › Medicine › Surgery › Helicobacter pylori-related gastroenterology studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
Keywords
Helicobacter pylori infection, NF-κB, inducible nitric oxide synthase, apoptosis, gastric epithelial cells, AGS cells, oxygen free radicals, peroxynitrite, catalase, pyrrolidine dithiocarbamate, nitric oxide, gastric ulcer, gastric carcinogenesis, antisense oligonucleotides
MeSH terms
Antioxidants, Catalase, Cell Line, Cell Survival, Enzyme Induction, Gastric Mucosa, Humans, Molsidomine, Nitroso Compounds, Pyrrolidines, Radiation-Protective Agents, Thiazines, Thiocarbamates, Gene Expression Regulation, Enzymologic, NF-kappa B, Helicobacter pylori, Helicobacter Infections, Apoptosis, Nitric Oxide Synthase, NG-Nitroarginine Methyl Ester, Nitric Oxide Donors, Oligodeoxyribonucleotides, Antisense, Nitric Oxide Synthase Type II

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