Abstract
Approximately 50% of Helicobacter pylori strains produce a toxin in vitro that induces vacuolation of eukaryotic cells. To determine whether ion transport pathways are important in the formation of toxin-induced vacuoles, HeLa cells were incubated with H. pylori toxin in the presence of nine different inhibitors of ion-transporting ATPases. Oligomycin, an inhibitor of predominantly F1F0-type ATPases, had no effect on toxin activity. Inhibitors of predominantly V-type ATPases, exemplified by bafilomycin A1, inhibited the formation of vacuoles in response to the H. pylori toxin and reversed the vacuolation induced by the toxin. In contrast, at concentrations of > or = 100 nM, ouabain and digoxin, inhibitors of the Na(+)-K+ ATPase, potentiated the activity of H. pylori toxin. The inhibitory effects of bafilomycin A1 could not be overcome by the potentiating effects of ouabain. These data suggest that intact activity of the vacuolar ATPase of eukaryotic cells is a critical requirement in the pathogenesis of cell vacuolation induced by H. pylori toxin and that vacuole formation by this toxin is associated with altered cation transport within eukaryotic cells.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adler S. Nondependence of cell pH on sodium transport in rat diaphragm muscle. Metabolism. 1975 Feb;24(2):183–188. doi: 10.1016/0026-0495(75)90019-0. [DOI] [PubMed] [Google Scholar]
- Al-Awqati Q. Proton-translocating ATPases. Annu Rev Cell Biol. 1986;2:179–199. doi: 10.1146/annurev.cb.02.110186.001143. [DOI] [PubMed] [Google Scholar]
- Bowman E. J. Comparison of the vacuolar membrane ATPase of Neurospora crassa with the mitochondrial and plasma membrane ATPases. J Biol Chem. 1983 Dec 25;258(24):15238–15244. [PubMed] [Google Scholar]
- Bowman E. J., Siebers A., Altendorf K. Bafilomycins: a class of inhibitors of membrane ATPases from microorganisms, animal cells, and plant cells. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7972–7976. doi: 10.1073/pnas.85.21.7972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cantley L. C., Jr, Resh M. D., Guidotti G. Vanadate inhibits the red cell (Na+, K+) ATPase from the cytoplasmic side. Nature. 1978 Apr 6;272(5653):552–554. doi: 10.1038/272552a0. [DOI] [PubMed] [Google Scholar]
- Cooke K. R. Ouabain and regulation of cellular volume in freshly prepared slices of rabbit renal cortex. J Physiol. 1978 Jun;279:361–374. doi: 10.1113/jphysiol.1978.sp012349. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cover T. L., Blaser M. J. Helicobacter pylori and gastroduodenal disease. Annu Rev Med. 1992;43:135–145. doi: 10.1146/annurev.me.43.020192.001031. [DOI] [PubMed] [Google Scholar]
- Cover T. L., Blaser M. J. Purification and characterization of the vacuolating toxin from Helicobacter pylori. J Biol Chem. 1992 May 25;267(15):10570–10575. [PubMed] [Google Scholar]
- Cover T. L., Cao P., Murthy U. K., Sipple M. S., Blaser M. J. Serum neutralizing antibody response to the vacuolating cytotoxin of Helicobacter pylori. J Clin Invest. 1992 Sep;90(3):913–918. doi: 10.1172/JCI115967. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cover T. L., Puryear W., Perez-Perez G. I., Blaser M. J. Effect of urease on HeLa cell vacuolation induced by Helicobacter pylori cytotoxin. Infect Immun. 1991 Apr;59(4):1264–1270. doi: 10.1128/iai.59.4.1264-1270.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cover T. L., Vaughn S. G., Cao P., Blaser M. J. Potentiation of Helicobacter pylori vacuolating toxin activity by nicotine and other weak bases. J Infect Dis. 1992 Nov;166(5):1073–1078. doi: 10.1093/infdis/166.5.1073. [DOI] [PubMed] [Google Scholar]
- Dean G. E., Fishkes H., Nelson P. J., Rudnick G. The hydrogen ion-pumping adenosine triphosphatase of platelet dense granule membrane. Differences from F1F0- and phosphoenzyme-type ATPases. J Biol Chem. 1984 Aug 10;259(15):9569–9574. [PubMed] [Google Scholar]
- Figura N., Guglielmetti P., Rossolini A., Barberi A., Cusi G., Musmanno R. A., Russi M., Quaranta S. Cytotoxin production by Campylobacter pylori strains isolated from patients with peptic ulcers and from patients with chronic gastritis only. J Clin Microbiol. 1989 Jan;27(1):225–226. doi: 10.1128/jcm.27.1.225-226.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Flatmark T., Grønberg M., Husebye E., Jr, Berge S. V. Inhibition of N-ethylmaleimide of the MgATP-driven proton pump of the chromaffin granules. FEBS Lett. 1982 Nov 22;149(1):71–74. doi: 10.1016/0014-5793(82)81074-0. [DOI] [PubMed] [Google Scholar]
- Harootunian A. T., Kao J. P., Eckert B. K., Tsien R. Y. Fluorescence ratio imaging of cytosolic free Na+ in individual fibroblasts and lymphocytes. J Biol Chem. 1989 Nov 15;264(32):19458–19467. [PubMed] [Google Scholar]
- Kaunitz J. D., Gunther R. D., Sachs G. Characterization of an electrogenic ATP and chloride-dependent proton translocating pump from rat renal medulla. J Biol Chem. 1985 Sep 25;260(21):11567–11573. [PubMed] [Google Scholar]
- Kim D., Cragoe E. J., Jr, Smith T. W. Relations among sodium pump inhibition, Na-Ca and Na-H exchange activities, and Ca-H interaction in cultured chick heart cells. Circ Res. 1987 Feb;60(2):185–193. doi: 10.1161/01.res.60.2.185. [DOI] [PubMed] [Google Scholar]
- Leunk R. D., Johnson P. T., David B. C., Kraft W. G., Morgan D. R. Cytotoxic activity in broth-culture filtrates of Campylobacter pylori. J Med Microbiol. 1988 Jun;26(2):93–99. doi: 10.1099/00222615-26-2-93. [DOI] [PubMed] [Google Scholar]
- Macknight A. D., Leaf A. Regulation of cellular volume. Physiol Rev. 1977 Jul;57(3):510–573. doi: 10.1152/physrev.1977.57.3.510. [DOI] [PubMed] [Google Scholar]
- Mattsson J. P., Vänänen K., Wallmark B., Lorentzon P. Omeprazole and bafilomycin, two proton pump inhibitors: differentiation of their effects on gastric, kidney and bone H(+)-translocating ATPases. Biochim Biophys Acta. 1991 Jun 18;1065(2):261–268. doi: 10.1016/0005-2736(91)90238-4. [DOI] [PubMed] [Google Scholar]
- Mellman I., Fuchs R., Helenius A. Acidification of the endocytic and exocytic pathways. Annu Rev Biochem. 1986;55:663–700. doi: 10.1146/annurev.bi.55.070186.003311. [DOI] [PubMed] [Google Scholar]
- Nomura A., Stemmermann G. N., Chyou P. H., Kato I., Perez-Perez G. I., Blaser M. J. Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med. 1991 Oct 17;325(16):1132–1136. doi: 10.1056/NEJM199110173251604. [DOI] [PubMed] [Google Scholar]
- Ohkuma S., Poole B. Cytoplasmic vacuolation of mouse peritoneal macrophages and the uptake into lysosomes of weakly basic substances. J Cell Biol. 1981 Sep;90(3):656–664. doi: 10.1083/jcb.90.3.656. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ohkuma S., Poole B. Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH by various agents. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3327–3331. doi: 10.1073/pnas.75.7.3327. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Peterson W. L. Helicobacter pylori and peptic ulcer disease. N Engl J Med. 1991 Apr 11;324(15):1043–1048. doi: 10.1056/NEJM199104113241507. [DOI] [PubMed] [Google Scholar]
- Roos A., Boron W. F. Intracellular pH. Physiol Rev. 1981 Apr;61(2):296–434. doi: 10.1152/physrev.1981.61.2.296. [DOI] [PubMed] [Google Scholar]
- Skou J. C. The Na,K-pump. Methods Enzymol. 1988;156:1–25. doi: 10.1016/0076-6879(88)56004-4. [DOI] [PubMed] [Google Scholar]
- Umata T., Moriyama Y., Futai M., Mekada E. The cytotoxic action of diphtheria toxin and its degradation in intact Vero cells are inhibited by bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase. J Biol Chem. 1990 Dec 15;265(35):21940–21945. [PubMed] [Google Scholar]
- Van Dyke R. W. Anion inhibition of the proton pump in rat liver multivesicular bodies. J Biol Chem. 1986 Dec 5;261(34):15941–15948. [PubMed] [Google Scholar]
- Van Dyke R. W., Hornick C. A., Belcher J., Scharschmidt B. F., Havel R. J. Identification and characterization of ATP-dependent proton transport by rat liver multivesicular bodies. J Biol Chem. 1985 Sep 15;260(20):11021–11026. [PubMed] [Google Scholar]
- Van Dyke R. W., Steer C. J., Scharschmidt B. F. Clathrin-coated vesicles from rat liver: enzymatic profile and characterization of ATP-dependent proton transport. Proc Natl Acad Sci U S A. 1984 May;81(10):3108–3112. doi: 10.1073/pnas.81.10.3108. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wallick E. T., Schwartz A. Interaction of cardiac glycosides with Na+,K+-ATPase. Methods Enzymol. 1988;156:201–213. doi: 10.1016/0076-6879(88)56022-6. [DOI] [PubMed] [Google Scholar]
- Yoshida T., Chen C. H., Zhang M. S., Wu H. C. Increased cytotoxicity of ricin in a putative Golgi-defective mutant of Chinese hamster ovary cell. Exp Cell Res. 1990 Sep;190(1):11–16. doi: 10.1016/0014-4827(90)90137-y. [DOI] [PubMed] [Google Scholar]
- Yoshimori T., Yamamoto A., Moriyama Y., Futai M., Tashiro Y. Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, inhibits acidification and protein degradation in lysosomes of cultured cells. J Biol Chem. 1991 Sep 15;266(26):17707–17712. [PubMed] [Google Scholar]