title: Helicobacter pylori vacuolating cytotoxin (VacA) alters cytoskeleton-associated proteins and interferes with re-epithelialization of wounded gastric epithelial monolayers.
abstract: In previous studies, we demonstrated that Helicobacter pylori vacuolating cytotoxin (VacA) inhibits gastric epithelial cell proliferation and inhibits epidermal growth factor (EGF)-activated signal transduction. Cell proliferation and migration, both essential for mucosal healing are dependent on the cell cytoskeleton. Other investigators demonstrated that VacA induces vacuolation of eukaryotic cells. Since in some cells, control of actin cytoskeleton involves GTP-binding proteins of Rho family, in this study we examined whether VacA affects wound re-epithelialization, cell cytoskeleton-associated proteins Rho, Rac1 in a gastric epithelial (RGM1) cell monolayer wound model, and whether these changes correlate with vacuolation. VacA treatment significantly inhibited wound re-epithelialization, cell proliferation vs control. VacA-induced cell vacuolation strongly correlated with inhibition of wound re-epithelialization. Furthermore, VacA reduced Rac-1 protein expression and distribution, and C3-mediated ADP-ribosylation of Rho. These findings suggest that VacA may interfere with repair of gastric mucosal injury and ulcer re-epithelialization by altering cytoskeleton-dependent cell functions and signaling.
authors.affiliation: Medical Service, Department of Veterans Affairs Medical Center, Long Beach, CA 90822, USA.
authors.forename: R
authors.initials: R
authors.lastname: Pai
authors.forename: E
authors.initials: E
authors.lastname: Sasaki
authors.forename: A S
authors.initials: AS
authors.lastname: Tarnawski
mesh_terms: D036002:ADP Ribose Transferases / Q000494:pharmacology; D000199:Actins / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism* / Q000494:pharmacology; D001427:Bacterial Toxins / Q000378:metabolism* / Q000494:pharmacology; D001905:Botulinum Toxins; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000187:drug effects / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D016480:Helicobacter pylori / Q000201:enzymology; D016685:Mitomycin / Q000494:pharmacology; D051381:Rats; D013312:Stress, Physiological / Q000378:metabolism; D014617:Vacuoles / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000199:Actins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D003598:Cytoskeletal Proteins; C074689:VacA protein, Helicobacter pylori; D016685:Mitomycin; D004247:DNA; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D001905:Botulinum Toxins; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins