NF-κB, inducible nitric oxide synthase and apoptosis by Helicobacter pylori infection
Open accessAbstract
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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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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Is stomach spontaneously ageing? Pathophysiology of the ageing stomach
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Angrisano, T., Lembo, F., Peluso, S., Keller, S., Chiariotti, L., & Pero, R. (2012) · Medical Microbiology and Immunology · doi:10.1007/s00430-011-0227-9 · Cited by 38 · see citing works
Cha, B., Lim, J. W., Kim, K. H., & Kim, H. (2010) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2010.04.015 · Cited by 37 · see citing works
Self-citationTrubiani, O., Salvolini, E., Staffolani, R., Primio, R. D., & Mazzanti, L. (2003) · International Journal of Immunopathology and Pharmacology · doi:10.1177/039463200301600311 · Cited by 36 · see citing works
Seo, J. H., Lim, J. W., & Kim, H. (2013) · Journal of Cancer Prevention · doi:10.15430/jcp.2013.18.4.346 · Cited by 32 · see citing works
Self-citationPark, H.-S., Wijerathne, C. U. B., Jeong, H.-Y., Seo, C., Ha, H., & Kwun, H. (2018) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2018.01.025 · Cited by 32 · see citing works
Oxidative stress in Helicobacter pylori-induced gastric cell injury
Kim, H. (2005) · Inflammopharmacology · doi:10.1163/156856005774423962 · Cited by 30 · see citing works
Self-citationChu, S. H., Lim, J. W., Kim, D. G., Lee, E.-S., Kim, K. H., & Kim, H. (2010) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365521.2010.525255 · Cited by 29 · see citing works
Self-citationKim, A., Lim, J. W., Kim, H., & Kim, H. (2016) · Nutrition Research · doi:10.1016/j.nutres.2015.12.017 · Cited by 29 · see citing works
Self-citationApoptosis in the Gastrointestinal Tract
Johnson, L. R. (2006) · Elsevier eBooks · doi:10.1016/b978-012088394-3/50015-5 · Cited by 29 · see citing works
Byun, E.-Y., Park, B., Lim, J. W., & Kim, H. (2016) · Yonsei Medical Journal · doi:10.3349/ymj.2016.57.3.647 · Cited by 26 · see citing works
Self-citationCurrent consensus on the diagnosis and treatment of H. pylori-associated gastroduodenal disease
Suzuki, H., Masaoka, T., Nomura, S., Hoshino, Y., Kurabayashi, K., Minegishi, Y., Suzuki, M., & Ishii, H. (2003) · The Keio Journal of Medicine · doi:10.2302/kjm.52.163 · Cited by 24 · see citing works
Vicaș, L. G., Jurca, T., Bâldea, I., Filip, G. A., Olteanu, D. E., Clichici, S. V., Pallag, A., Marian, E., Micle, O., Crivii, C. B., et al. (2020) · Molecules · doi:10.3390/molecules25163747 · Cited by 23 · see citing works
Oxidative Stress In Helicobacter pylori-Assocaited Gastroduodenal Disease
Suzuki, H., & Hibi∥, T. (2006) · Journal of Clinical Biochemistry and Nutrition · doi:10.3164/jcbn.39.56 · Cited by 21 · see citing works
Jy, S., Jh, Y., Jw, L., Mukaida, N., & Kim, H. (2009) · PubMed · Cited by 20 · see citing works
Self-citationKim, H., Seo, J. H., & Kim, K. H. (2003) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1299.014 · Cited by 19 · see citing works
Self-citationThe Bactericidal and Morphological Effects of Peroxynitrite on Helicobacter pylori
Ünal, M. T., Can, F., Demirbilek, M., Karabay, G., Tufan, H., & Arslan, H. (2008) · Helicobacter · doi:10.1111/j.1523-5378.2008.00583.x · Cited by 18 · see citing works
Lu, M.-C., Chiu, H., Lin, C.-P., Shen, Y., Venkatakrishnan, K., & Wang, C. (2017) · Journal of Herbal Medicine · doi:10.1016/j.hermed.2017.08.002 · Cited by 17 · see citing works
Current management ofHelicobacter pyloriinfections in the elderly
Salles, N., & Mégraud, F. (2007) · Expert Review of Anti-infective Therapy · doi:10.1586/14787210.5.5.845 · Cited by 17 · see citing works
Helicobacter pylori infection: pathogenesis
Panchal, P. C., Forman, J., Blumberg, D. R., & Wilson, K. T. (2003) · Current Opinion in Gastroenterology · doi:10.1097/00001574-200301000-00002 · Cited by 17 · see citing works
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NF‐κB and Bcl‐2 in Helicobacter pylori ‐Induced Apoptosis in Gastric Epithelial Cells
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Self-citationNitric oxide in Helicobacter pylori‐induced apoptosis and its significance in gastric carcinogenesis
Xia, H. H., & Yu, W. B. C. (2003) · Journal of Gastroenterology and Hepatology · doi:10.1046/j.1440-1746.2003.03147.x · Cited by 7 · see citing works
Infection à Helicobacter pylori chez la personne âgée
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Diabetes and Its Hepatic Complication
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Programmed Cell Death in the Gastrointestinal Tract
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Free Radicals in Helicobacter pylori Infection
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Molecular Targets for Antiinflammation and Dietary Component-Drug Synergy
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Molecular Targets for Antiinflammation and Dietary Component—Drug Synergy
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Nguyen, T. T. T., Vo, H. M. P., Pham, D. T.-H., & Nguyen, T.-V. (2026) · Human Gene · doi:10.1016/j.humgen.2026.201597
- 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
- Licence
- 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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