Vacuolation induced by VacA toxin of Helicobacter pylori requires the intracellular accumulation of membrane permeant bases, Cl− and water

FEBS Letters

Del Giudice, Giuseppe²  Tombola, Francesco¹  Zoratti, Mario¹  Campello, Silvia¹  Morbiato, Laura¹  Papini, Emanuele³  Rappuoli, Rino² 

[1] Centro CNR Biomembrane, Department of Biomedical Sciences, University of Padova, V.le G. Colombo 3, 35121 Padua, Italy;Immunobiology Research Institute Siena, Chiron-Vaccines, Via Fiorentina 1, 53100 Siena, Italy;Department of Biomedical Sciences and Human Oncology, University of Bari, Section of General Pathology, P.zza G. Cesare 11, 70124 Bari, Italy

关键词: Cell vacuolation;    Cl− transport;    Na+;    K+;    2Cl− cotransporter;    VacA anion channel;    Helicobacter pylori;    BSA;    bovine serum albumin;    DMEM;    Dulbecco's modified Eagle medium;    FCS;    fetal calf serum;    NKCC;    Na+;    K+;    2Cl− cotransporter;    NRU;    neutral red uptake;    PBS;    phosphate-buffered saline;    VacA;    vacuolating toxin A;    V-ATPase;    vacuolar-type ATPase;   

DOI  :  10.1016/S0014-5793(01)03133-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown