Abstract
The protein vacuolating toxin A (VacA) of Helicobacter pylori converts late endosomes into large vacuoles in the presence of permeant bases. Here it is shown that this phenomenon corresponds to an accumulation of permeant bases and Cl(-) in HeLa cells and requires the presence of extracellular Cl(-). The net influx of Cl(-) is due to electroneutral, Na(+), K(+), 2Cl(-) cotransporter-mediated transport. Cell vacuolation leads to cell volume increase, consistent with water flux into the cell, while hyper-osmotic media decreased vacuole formation. These data represent the first evidence that VacA-treated cells undergo an osmotic unbalance, reinforcing the hypothesis that the VacA chloride channel is responsible for cell vacuolation.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Ammonium Chloride / pharmacology
-
Bacterial Proteins / metabolism
-
Bacterial Proteins / toxicity*
-
Bumetanide / pharmacology
-
Cell Membrane Permeability
-
Cell Size
-
Chlorides / metabolism*
-
Endosomes / metabolism
-
HeLa Cells
-
Helicobacter pylori*
-
Humans
-
Hydrogen-Ion Concentration
-
Methylamines / metabolism
-
Osmotic Pressure
-
Sodium Potassium Chloride Symporter Inhibitors
-
Sodium-Potassium-Chloride Symporters / metabolism
-
Vacuoles / drug effects
-
Vacuoles / metabolism*
-
Water / metabolism*
Substances
-
Bacterial Proteins
-
Chlorides
-
Methylamines
-
Sodium Potassium Chloride Symporter Inhibitors
-
Sodium-Potassium-Chloride Symporters
-
VacA protein, Helicobacter pylori
-
Ammonium Chloride
-
Water
-
Bumetanide
-
methylamine