This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shibayama, K.
Right arrow Articles by Arakawa, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shibayama, K.
Right arrow Articles by Arakawa, Y.

 Previous Article  |  Next Article 

Infection and Immunity, May 2001, p. 3181-3189, Vol. 69, No. 5
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.5.3181-3189.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Apoptotic Signaling Pathway Activated by Helicobacter pylori Infection and Increase of Apoptosis-Inducing Activity under Serum-Starved Conditions

Keigo Shibayama,1,* Yohei Doi,1 Naohiro Shibata,1 Tetsuya Yagi,1 Toshi Nada,2 Yoshitsugu Iinuma,2 and Yoshichika Arakawa1

Department of Bacterial and Blood Products, National Institute of Infectious Diseases, Tokyo 208-0011,1 and Department of Clinical Laboratory, Nagoya University Hospital, Nagoya 466-8560,2 Japan

Received 21 November 2000/Returned for modification 15 January 2001/Accepted 19 February 2001

The enhanced gastric epithelial cell apoptosis observed during infection with Helicobacter pylori has been suggested to be of significance in the etiology of gastritis, peptic ulcers, and neoplasia. To investigate the cell death signaling induced by H. pylori infection, human gastric epithelial cells were incubated with H. pylori for up to 72 h. H. pylori infection induced the activation of caspase -8, -9, and -3 and the expression of the proapoptotic Bcl-2 family proteins Bad and Bid. The peak of the activity of the caspases occurred at 24 h. At this time, the inhibition of caspase-8 or -9 almost completely suppressed H. pylori-induced apoptosis. Inhibition of caspase-8 suppressed the expression of Bad and Bid and the subsequent activation of caspase-9 and -3. These observations indicate that H. pylori induces apoptosis through a pathway involving the sequential induction of apical caspase-8 activity, the proapoptotic proteins Bad and Bid, caspase-9 activity, and effector caspase-3 activity. Activation of the pathway was independent of CagA or vacuolating toxin. A membrane fraction of H. pylori was sufficient to activate this pathway, and treatment with proteinase K eliminated the activity. Apoptotic activity of the membrane fraction was significantly increased by incubating the bacteria under serum-starved conditions for 24 h. These observations suggest that environmental conditions in the human stomach could induce H. pylori-mediated pathogenesis, leading to a variety of clinical outcomes.

* Corresponding author. Mailing address: Department of Bacterial and Blood Products, National Institute of Infectious Diseases, 4-7-1, Gakuen, Musashimurayama, Tokyo 208-0011, Japan. Phone: 81-42-561-0771. Fax: 81-42-561-7173. E-mail: keigo{at}nih.go.jp.

Infection and Immunity, May 2001, p. 3181-3189, Vol. 69, No. 5
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.5.3181-3189.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Ding, S.-Z., Minohara, Y., Fan, X. J., Wang, J., Reyes, V. E., Patel, J., Dirden-Kramer, B., Boldogh, I., Ernst, P. B., Crowe, S. E. (2007). Helicobacter pylori Infection Induces Oxidative Stress and Programmed Cell Death in Human Gastric Epithelial Cells. Infect. Immun. 75: 4030-4039 [Abstract] [Full Text]  
  • Tsai, W.-H., Chang, C.-W., Chuang, W.-J., Lin, Y.-S., Wu, J.-J., Liu, C.-C., Chang, W.-T., Lin, M. T. (2004). Streptococcal Pyrogenic Exotoxin B-Induced Apoptosis in A549 Cells Is Mediated by a Receptor- and Mitochondrion-Dependent Pathway. Infect. Immun. 72: 7055-7062 [Abstract] [Full Text]  
  • Ashktorab, H, Frank, S, Khaled, A R, Durum, S K, Kifle, B, Smoot, D T (2004). Bax translocation and mitochondrial fragmentation induced by Helicobacter pylori. Gut 53: 805-813 [Abstract] [Full Text]  
  • Menaker, R. J., Ceponis, P. J. M., Jones, N. L. (2004). Helicobacter pylori Induces Apoptosis of Macrophages in Association with Alterations in the Mitochondrial Pathway. Infect. Immun. 72: 2889-2898 [Abstract] [Full Text]  
  • Joshi, S. G., Francis, C. W., Silverman, D. J., Sahni, S. K. (2003). Nuclear Factor {kappa}B Protects against Host Cell Apoptosis during Rickettsia rickettsii Infection by Inhibiting Activation of Apical and Effector Caspases and Maintaining Mitochondrial Integrity. Infect. Immun. 71: 4127-4136 [Abstract] [Full Text]  
  • Ibata-Ombetta, S., Idziorek, T., Trinel, P.-A., Poulain, D., Jouault, T. (2003). Candida albicans Phospholipomannan Promotes Survival of Phagocytosed Yeasts through Modulation of Bad Phosphorylation and Macrophage Apoptosis. J. Biol. Chem. 278: 13086-13093 [Abstract] [Full Text]  
  • Yang, Y, Deng, C S, Peng, J Z, Wong, B C-Y, Lam, S K, Xia, H H-X (2003). Effect of Helicobacter pylori on apoptosis and apoptosis related genes in gastric cancer cells. Mol. Pathol. 56: 19-24 [Abstract] [Full Text]  
  • Le'Negrate, G., Ricci, V., Hofman, V., Mograbi, B., Hofman, P., Rossi, B. (2001). Epithelial Intestinal Cell Apoptosis Induced by Helicobacter pylori Depends on Expression of the cag Pathogenicity Island Phenotype. Infect. Immun. 69: 5001-5009 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»