Cancer Research Annual Meeting 2010 Telomeres
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
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 Email this article to a friend
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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cover, T. L.
Right arrow Articles by Peek, R. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cover, T. L.
Right arrow Articles by Peek, R. M., Jr.
[Cancer Research 63, 951-957, March 1, 2003]
© 2003 American Association for Cancer Research

Carcinogenesis

Induction of Gastric Epithelial Cell Apoptosis by Helicobacter pylori Vacuolating Cytotoxin1

Timothy L. Cover, Uma S. Krishna, Dawn A. Israel and Richard M. Peek, Jr.2

Division of Infectious Diseases, Departments of Medicine and Microbiology and Immunology [T. L. C.], and Division of Gastroenterology, Departments of Medicine and Cancer Biology [U. S. K., D. A. I., R. M. P.], Vanderbilt University School of Medicine, Nashville, Tennessee 3722-2605, and Department of Veterans Affairs Medical Center, Nashville, Tennessee 37212 [T. L. C., R. M. P.]

Chronic gastritis induced by Helicobacter pylori is a strong risk factor for thedevelopment of distal gastric adenocarcinoma. A specific host response to H. pylori that may contribute to gastric carcinogenesis is epithelial cell apoptosis. The aim of this study was to investigate the capacity of H. pylori vacuolating toxin (VacA) to induce gastric epithelial cell apoptosis. When cocultured with AGS gastric epithelial cells, H. pylori strain 60190, which expresses a type s1/m1 VacA toxin, induced significantly higher levels of apoptosis than did an isogenic vacA null mutant strain. VacA purified from strain 60190 induced apoptosis in a dose-dependent manner, which required acid activation of the purified toxin and the presence of ammonium chloride. In contrast, apoptosis was not induced after incubation with a chimeric s2/m1 toxin (in which the s1 sequence at the NH2 terminus of VacA from strain 60190 was replaced with the s2 sequence from the nontoxigenic strain Tx30a) or a VacA mutant protein (VacA {Delta}6–27) that lacks a unique strongly hydrophobic region near the VacA NH2 terminus. Moreover, when an equimolar mixture of purified VacA {Delta}6–27 and purified wild-type VacA were added simultaneously to AGS cells, the mutant toxin exhibited a dominant negative effect, completely inhibiting the apoptosis-inducing activity of wild-type VacA. These results indicate that VacA induces gastric epithelial cell apoptosis and suggest that differences in levels of gastric mucosal epithelial apoptosis among H. pylori-infected persons may result from strain-dependent variations in VacA structure.




This article has been cited by other articles:


Home page
 Mol. Cell. ProteomicsHome page
A. T. Franco, D. B. Friedman, T. A. Nagy, J. Romero-Gallo, U. Krishna, A. Kendall, D. A. Israel, N. Tegtmeyer, M. K. Washington, and R. M. Peek Jr.
Delineation of a Carcinogenic Helicobacter pylori Proteome
Mol. Cell. Proteomics, August 1, 2009; 8(8): 1947 - 1958.
[Abstract] [Full Text] [PDF]

Home page
 Anticancer ResHome page
M.-R. KI, I.-H. HONG, J.-K. PARK, K.-S. HONG, O.-K. HWANG, J.-Y. HAN, A.-R. JI, S.-I. PARK, S.-K. LEE, S.-E. YOO, et al.
Potent Neutralization of Vacuolating Cytotoxin (VacA) of Helicobacter pylori by Immunoglobulins Against the Soluble Recombinant VacA
Anticancer Res, June 1, 2009; 29(6): 2393 - 2402.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Microbiol. Rev.Home page
F. Haesebrouck, F. Pasmans, B. Flahou, K. Chiers, M. Baele, T. Meyns, A. Decostere, and R. Ducatelle
Gastric Helicobacters in Domestic Animals and Nonhuman Primates and Their Significance for Human Health
Clin. Microbiol. Rev., April 1, 2009; 22(2): 202 - 223.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
N. P. Tobin, G. T. Henehan, R. P. Murphy, J. C. Atherton, A. F. Guinan, S. W. Kerrigan, D. Cox, P. A. Cahill, and P. M. Cummins
Helicobacter pylori-induced inhibition of vascular endothelial cell functions: a role for VacA-dependent nitric oxide reduction
Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1403 - H1413.
[Abstract] [Full Text] [PDF]

Home page
 DMMHome page
R. M. Peek Jr
Helicobacter pylori infection and disease: from humans to animal models
Dis. Model. Mech., July 1, 2008; 1(1): 50 - 55.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M.-R. Ki, H.-R. Lee, M.-J. Goo, I.-H. Hong, S.-H. Do, D.-H. Jeong, H.-J. Yang, D.-W. Yuan, J.-K. Park, and K.-S. Jeong
Differential regulation of ERK1/2 and p38 MAP kinases in VacA-induced apoptosis of gastric epithelial cells
Am J Physiol Gastrointest Liver Physiol, March 1, 2008; 294(3): G635 - G647.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. T. Franco, E. Johnston, U. Krishna, Y. Yamaoka, D. A. Israel, T. A. Nagy, L. E. Wroblewski, M. B. Piazuelo, P. Correa, and R. M. Peek Jr.
Regulation of Gastric Carcinogenesis by Helicobacter pylori Virulence Factors
Cancer Res., January 15, 2008; 68(2): 379 - 387.
[Abstract] [Full Text] [PDF]

Home page
 J Med MicrobiolHome page
G. Ayala, J. Torres-Mena, and L. Lopez-Carrillo
Association between Helicobacter pylori VacA antigens and gastric cancer depends on the detection method used: immunoblot versus neutralization of the vacuolating activity of VacA
J. Med. Microbiol., January 1, 2008; 57(1): 9 - 14.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
J. Hisatsune, E. Yamasaki, M. Nakayama, D. Shirasaka, H. Kurazono, Y. Katagata, H. Inoue, J. Han, J. Sap, K. Yahiro, et al.
Helicobacter pylori VacA Enhances Prostaglandin E2 Production through Induction of Cyclooxygenase 2 Expression via a p38 Mitogen-Activated Protein Kinase/Activating Transcription Factor 2 Cascade in AZ-521 Cells
Infect. Immun., September 1, 2007; 75(9): 4472 - 4481.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Pathol.Home page
V. Hofman, S. Lassalle, E. Selva, K. Kalem, A. Steff, X. Hebuterne, D. Sicard, P. Auberger, and P. Hofman
Involvement of mast cells in gastritis caused by Helicobacter pylori: a potential role in epithelial cell apoptosis
J. Clin. Pathol., June 1, 2007; 60(6): 600 - 607.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. Caruso, D. Fina, I. Peluso, M. C. Fantini, C. Tosti, G. D. V. Blanco, O. A. Paoluzi, F. Caprioli, F. Andrei, C. Stolfi, et al.
IL-21 Is Highly Produced in Helicobacter pylori-Infected Gastric Mucosa and Promotes Gelatinases Synthesis
J. Immunol., May 1, 2007; 178(9): 5957 - 5965.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
A. Izzotti, S. De Flora, C. Cartiglia, B. M. Are, M. Longobardi, A. Camoirano, I. Mura, M. P. Dore, A. M. Scanu, P. C. Rocca, et al.
Interplay between Helicobacter pylori and host gene polymorphisms in inducing oxidative DNA damage in the gastric mucosa
Carcinogenesis, April 1, 2007; 28(4): 892 - 898.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. Matarrese, L. Falzano, A. Fabbri, L. Gambardella, C. Frank, B. Geny, M. R. Popoff, W. Malorni, and C. Fiorentini
Clostridium difficile Toxin B Causes Apoptosis in Epithelial Cells by Thrilling Mitochondria: INVOLVEMENT OF ATP-SENSITIVE MITOCHONDRIAL POTASSIUM CHANNELS
J. Biol. Chem., March 23, 2007; 282(12): 9029 - 9041.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
H. M. S. Algood, V. J. Torres, D. Unutmaz, and T. L. Cover
Resistance of Primary Murine CD4+ T Cells to Helicobacter pylori Vacuolating Cytotoxin
Infect. Immun., January 1, 2007; 75(1): 334 - 341.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
M. R. Terebiznik, C. L. Vazquez, K. Torbicki, D. Banks, T. Wang, W. Hong, S. R. Blanke, M. I. Colombo, and N. L. Jones
Helicobacter pylori VacA Toxin Promotes Bacterial Intracellular Survival in Gastric Epithelial Cells
Infect. Immun., December 1, 2006; 74(12): 6599 - 6614.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
M. Nakayama, J. Hisatsune, E. Yamasaki, Y. Nishi, A. Wada, H. Kurazono, J. Sap, K. Yahiro, J. Moss, and T. Hirayama
Clustering of Helicobacter pylori VacA in Lipid Rafts, Mediated by Its Receptor, Receptor-Like Protein Tyrosine Phosphatase {beta}, Is Required for Intoxication in AZ-521 Cells
Infect. Immun., December 1, 2006; 74(12): 6571 - 6580.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Microbiol. Rev.Home page
J. G. Kusters, A. H. M. van Vliet, and E. J. Kuipers
Pathogenesis of Helicobacter pylori Infection
Clin. Microbiol. Rev., July 1, 2006; 19(3): 449 - 490.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
L. Falzano, P. Filippini, S. Travaglione, A. G. Miraglia, A. Fabbri, and C. Fiorentini
Escherichia coli Cytotoxic Necrotizing Factor 1 Blocks Cell Cycle G2/M Transition in Uroepithelial Cells
Infect. Immun., July 1, 2006; 74(7): 3765 - 3772.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. P. O'Brien, D. A. Israel, U. Krishna, J. Romero-Gallo, J. Nedrud, M. E. Medof, F. Lin, R. Redline, D. M. Lublin, B. J. Nowicki, et al.
The Role of Decay-accelerating Factor as a Receptor for Helicobacter pylori and a Mediator of Gastric Inflammation
J. Biol. Chem., May 12, 2006; 281(19): 13317 - 13323.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Yamasaki, A. Wada, A. Kumatori, I. Nakagawa, J. Funao, M. Nakayama, J. Hisatsune, M. Kimura, J. Moss, and T. Hirayama
Helicobacter pylori Vacuolating Cytotoxin Induces Activation of the Proapoptotic Proteins Bax and Bak, Leading to Cytochrome c Release and Cell Death, Independent of Vacuolation
J. Biol. Chem., April 21, 2006; 281(16): 11250 - 11259.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
V. J. Torres, M. S. McClain, and T. L. Cover
Mapping of a Domain Required for Protein-Protein Interactions and Inhibitory Activity of a Helicobacter pylori Dominant-Negative VacA Mutant Protein
Infect. Immun., April 1, 2006; 74(4): 2093 - 2101.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
C. Genisset, C. L. Galeotti, P. Lupetti, D. Mercati, D. A. G. Skibinski, S. Barone, R. Battistutta, M. de Bernard, and J. L. Telford
A Helicobacter pylori Vacuolating Toxin Mutant That Fails To Oligomerize Has a Dominant Negative Phenotype
Infect. Immun., March 1, 2006; 74(3): 1786 - 1794.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
D. Pinto-Santini and N. R. Salama
The Biology of Helicobacter pylori Infection, a Major Risk Factor for Gastric Adenocarcinoma
Cancer Epidemiol. Biomarkers Prev., August 1, 2005; 14(8): 1853 - 1858.
[Abstract] [Full Text] [PDF]

Home page
 JDRHome page
C.W. Kaplan, R. Lux, T. Huynh, A. Jewett, W. Shi, and S. K. Haake
Fusobacterium nucleatum Apoptosis-inducing Outer Membrane Protein
Journal of Dental Research, August 1, 2005; 84(8): 700 - 704.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
V. J. Torres, S. E. Ivie, M. S. McClain, and T. L. Cover
Functional Properties of the p33 and p55 Domains of the Helicobacter pylori Vacuolating Cytotoxin
J. Biol. Chem., June 3, 2005; 280(22): 21107 - 21114.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Yahiro, A. Wada, E. Yamasaki, M. Nakayama, Y. Nishi, J. Hisatsune, N. Morinaga, J. Sap, M. Noda, J. Moss, et al.
Essential Domain of Receptor Tyrosine Phosphatase {beta} (RPTP{beta}) for Interaction with Helicobacter pylori Vacuolating Cytotoxin
J. Biol. Chem., December 3, 2004; 279(49): 51013 - 51021.
[Abstract] [Full Text] [PDF]

Home page
 J BiochemHome page
A. Wada, E. Yamasaki, and T. Hirayama
Helicobacter pylori Vacuolating Cytotoxin, VacA, Is Responsible for Gastric Ulceration
J. Biochem., December 1, 2004; 136(6): 741 - 746.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
M. Galgani, I. Busiello, S. Censini, S. Zappacosta, L. Racioppi, and R. Zarrilli
Helicobacter pylori Induces Apoptosis of Human Monocytes but Not Monocyte-Derived Dendritic Cells: Role of the cag Pathogenicity Island
Infect. Immun., August 1, 2004; 72(8): 4480 - 4485.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
O. Yilmaz, T. Jungas, P. Verbeke, and D. M. Ojcius
Activation of the Phosphatidylinositol 3-Kinase/Akt Pathway Contributes to Survival of Primary Epithelial Cells Infected with the Periodontal Pathogen Porphyromonas gingivalis
Infect. Immun., July 1, 2004; 72(7): 3743 - 3751.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. S. Sundrud, V. J. Torres, D. Unutmaz, and T. L. Cover
Inhibition of primary human T cell proliferation by Helicobacter pylori vacuolating toxin (VacA) is independent of VacA effects on IL-2 secretion
PNAS, May 18, 2004; 101(20): 7727 - 7732.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
Y. Li, A. Wandinger-Ness, J. R. Goldenring, and T. L. Cover
Clustering and Redistribution of Late Endocytic Compartments in Response to Helicobacter pylori Vacuolating Toxin
Mol. Biol. Cell, April 1, 2004; 15(4): 1946 - 1959.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Nakayama, M. Kimura, A. Wada, K. Yahiro, K.-i. Ogushi, T. Niidome, A. Fujikawa, D. Shirasaka, N. Aoyama, H. Kurazono, et al.
Helicobacter pylori VacA Activates the p38/Activating Transcription Factor 2-mediated Signal Pathway in AZ-521 Cells
J. Biol. Chem., February 20, 2004; 279(8): 7024 - 7028.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
V. J. Torres, M. S. McClain, and T. L. Cover
Interactions between p-33 and p-55 Domains of the Helicobacter pylori Vacuolating Cytotoxin (VacA)
J. Biol. Chem., January 16, 2004; 279(3): 2324 - 2331.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. C. Willhite, T. L. Cover, and S. R. Blanke
Cellular Vacuolation and Mitochondrial Cytochrome c Release Are Independent Outcomes of Helicobacter pylori Vacuolating Cytotoxin Activity That Are Each Dependent on Membrane Channel Formation
J. Biol. Chem., November 28, 2003; 278(48): 48204 - 48209.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
S. Ismail, M. B. Hampton, and J. I. Keenan
Helicobacter pylori Outer Membrane Vesicles Modulate Proliferation and Interleukin-8 Production by Gastric Epithelial Cells
Infect. Immun., October 1, 2003; 71(10): 5670 - 5675.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2003 by the American Association for Cancer Research.