TPA and butyrate increase cell sensitivity to the vacuolating toxin of Helicobacter pylori.
The Helicobacter pylori toxin VacA induces large membrane-bound vacuolar compartments of late endosomal/lysosomal origin. Pre-treatment of cells with TPA and butyrate enhances the toxin induced vacuolisation up to 20 times, depending on the cell line, whereas other differentiating factors such as DMSO, EGF, valeric and retinoic acid have no effect. The higher toxin sensitivity induced by TPA does not result from an increased surface binding or endocytosis. The effect of TPA is apparent after several hours from addition and is inhibited by a PKC specific inhibitor. These data suggest that expression of cellular proteins, other than the toxin receptor(s), influences the vacuolating activity of VacA and may contribute to the sensitivity of different cell lines. The present findings define the most sensitive in vitro assay of the activity of VacA.
de Bernard
M
M
Centro CNR Biomembrane and Dipartimento di Scienze Biomediche dell'Università di Padova, Padua, Italy.
Moschioni
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M
Papini
E
E
Telford
J L
JL
Rappuoli
R
R
Montecucco
C
C
D000818:Animals; D001426:Bacterial Proteins / Q000493:pharmacokinetics / Q000633:toxicity*; D001427:Bacterial Toxins / Q000493:pharmacokinetics / Q000633:toxicity*; D001692:Biological Transport; D002087:Butyrates / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002522:Chlorocebus aethiops; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004285:Dogs; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D018922:HL-60 Cells; D006367:HeLa Cells; D016480:Helicobacter pylori; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D010421:Pentanoic Acids / Q000494:pharmacology; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology; D014617:Vacuoles / Q000187:drug effects / Q000502:physiology*; D014709:Vero Cells
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D002087:Butyrates; D010421:Pentanoic Acids; C074689:VacA protein, Helicobacter pylori; D014212:Tretinoin; D004815:Epidermal Growth Factor; C038780:n-pentanoic acid; D013755:Tetradecanoylphorbol Acetate; D004121:Dimethyl Sulfoxide