title: The Helicobacter pylori's protein VacA has direct effects on the regulation of cell cycle and apoptosis in gastric epithelial cells.
abstract: In this study, we have evaluated the effects on cell cycle regulation of VacA alone and in combination with other two Helicobacter pylori proteins, cytotoxin-associated protein (CagA) and HspB, using the human gastric epithelial cells (AGS). Our results indicate that VacA alone was able to inhibit the G1 to S progression of the cell cycle. The VacA capacity of inhibiting cell progression from G1 to S phase was also observed when cells were co-transfected with CagA or HspB. Moreover, VacA over-expression caused apoptosis in AGS cells through activation of caspase 8 and even more of caspase 9, thus indicating an involvement of both the receptor-mediated and the mitochondrial pathways of apoptosis. Indeed, the two pathways probably can co-operate to execute cell death with a prevalence of the mitochondrial pathways. Our data taken together provide additional information to further enhance our understanding of the molecular mechanism by which H. pylori proteins alter the growth status of human gastric epithelial cells.
authors.affiliation: Department of Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Manente
authors.forename: A
authors.initials: A
authors.lastname: Perna
authors.forename: E
authors.initials: E
authors.lastname: Buommino
authors.forename: L
authors.initials: L
authors.lastname: Altucci
authors.forename: A
authors.initials: A
authors.lastname: Lucariello
authors.forename: G
authors.initials: G
authors.lastname: Citro
authors.forename: A
authors.initials: A
authors.lastname: Baldi
authors.forename: G
authors.initials: G
authors.lastname: Iaquinto
authors.forename: M A
authors.initials: MA
authors.lastname: Tufano
authors.forename: A
authors.initials: A
authors.lastname: De Luca
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism; D017209:Apoptosis; D001426:Bacterial Proteins / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle; D002460:Cell Line; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000166:cytology* / Q000201:enzymology; D005434:Flow Cytometry; D006360:Heat-Shock Proteins / Q000378:metabolism; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D016160:Retinoblastoma Protein / Q000378:metabolism; D013270:Stomach / Q000166:cytology* / Q000201:enzymology; D014162:Transfection