Cellular Vacuolation and Mitochondrial Cytochrome c Release Are Independent Outcomes of Helicobacter pylori Vacuolating Cytotoxin Activity That Are Each Dependent on Membrane Channel Formation

Helicobacter pylori vacuolating cytotoxin A (VacA) engages the mitochondrial fission machinery to induce host cell death

“…Studies indicating the involvement of an extracellular, heatlabile factor in Hp-mediated mitochondrial network fragmentation prompted us to evaluate a potential role for VacA, which has been previously reported to modulate mitochondrial function (16,17,24,25). In contrast to the extensive fragmentation of mitochondria induced by Hp 60190 (Fig.…”

Helicobacter pylori Vacuolating Cytotoxin Induces Activation of the Proapoptotic Proteins Bax and Bak, Leading to Cytochrome c Release and Cell Death, Independent of Vacuolation

“…Another study showed that microinjection of DNA encoding VacA-green fluorescent protein (GFP) 3 fusion protein or p37 fragment-GFP fusion protein induced apoptosis of Hep-2 cells (17), and transfection of HeLa cells with these DNAs resulted in the release of cytochrome c from mitochondria plus activation of caspase 3. Willhite et al (18) and Nakayama et al (19) also reported that VacA purified from H. pylori culture medium induced cytochrome c release in HeLa and AZ-521 gastric epithelial cells, suggesting that VacA induced apoptosis via a mitochondria-dependent pathway. VacA also caused mitochondrial damage, leading to a decrease in mitochondrial membrane potential (20,21).…”

Effect ofHelicobacter pylori’s vacuolating cytotoxin on the autophagy pathway in gastric epithelial cells

“…Prior to utilization, concentrated culture media supernatants (CCMS) were further diluted 5 times in Ham's F-12 cell culture media with 10% FBS. 9 VacA was purified from culture supernatants obtained from H. pylori strains 60190 (ATCC 49503; cagA + cagE + s1m1 VacA + ), the corresponding channel forming mutants VacA P9A and G14A 38 or Tx30A (s2m2 VacA + ). 39 Purified VacA toxin (inactive) was activated by incubation in acidified Ham's F12 culture media, pH 2, for 30 minutes at 37°C.…”