TY - JOUR
T1 - H. pylori-induced apoptosis in human gastric cancer cells mediated via the release of apoptosis-inducing factor from mitochondria
AU - Ashktorab, Hassan
AU - Dashwood, Rod H.
AU - Dashwood, Mohaiza M.
AU - Zaidi, Syed I.
AU - Hewitt, Stephen M.
AU - Green, William R.
AU - Lee, Edward L.
AU - Daremipouran, Mohammadreza
AU - Nouraie, Mehdi
AU - Malekzadeh, Reza
AU - Smoot, Duane T.
PY - 2008/12
Y1 - 2008/12
N2 - Background and Aim: Our previous study of Helicobacter pylori-induced apoptosis showed the involvement of Bcl-2 family proteins and cytochrome c release from mitochondria. Here, we examine the release of other factors from mitochondria, such as apoptosis-inducing factor (AIF), and upstream events involving caspase-8 and Bid. Methods: Human gastric adenocarcinoma (AGS) cells were incubated with a cagA-positive H. pylori strain for 0, 3, 6, and 24 hours and either total protein or cytoplasmic, nuclear, and mitochondrial membrane fractions were collected. Results: Proteins were immunoblotted for AIF, Bid, polyadenosine ribose polymerase (PARP), caspase-8, and β-catenin. H. pylori activated caspase-8, caused PARP cleavage, and attenuated mitochondrial membrane potential. A time-dependent decrease in β-catenin protein expression was detected in cytoplasmic and nuclear extracts, coupled with a decrease in β-actin. An increase in the cytoplasmic pool of AIF was seen as early as 3 hours after H. pylori exposure, and a concomitant increase was seen in nuclear AIF levels up to 6 hours. A band corresponding to full-length Bid was seen in both the cytoplasmic and the nuclear fractions of controls, but not after H. pylori exposure. Active AIF staining was markedly increased in gastric mucosa from infected persons, compared to uninfected controls. Conclusion: H. pylori might trigger apoptosis in AGS cells via interaction with death receptors in the plasma membrane, leading to the cleavage of procaspase-8, release of cytochrome c and AIF from mitochondria, and activation of subsequent downstream apoptotic events, as reported previously for chlorophyllin. This is consistent with AIF activation that was found in the gastric mucosa of humans infected with H. pylori. Hence, the balance between apoptosis and proliferation in these cells may be altered in response to injury caused by H. pylori infection, leading to an increased risk of cancer.
AB - Background and Aim: Our previous study of Helicobacter pylori-induced apoptosis showed the involvement of Bcl-2 family proteins and cytochrome c release from mitochondria. Here, we examine the release of other factors from mitochondria, such as apoptosis-inducing factor (AIF), and upstream events involving caspase-8 and Bid. Methods: Human gastric adenocarcinoma (AGS) cells were incubated with a cagA-positive H. pylori strain for 0, 3, 6, and 24 hours and either total protein or cytoplasmic, nuclear, and mitochondrial membrane fractions were collected. Results: Proteins were immunoblotted for AIF, Bid, polyadenosine ribose polymerase (PARP), caspase-8, and β-catenin. H. pylori activated caspase-8, caused PARP cleavage, and attenuated mitochondrial membrane potential. A time-dependent decrease in β-catenin protein expression was detected in cytoplasmic and nuclear extracts, coupled with a decrease in β-actin. An increase in the cytoplasmic pool of AIF was seen as early as 3 hours after H. pylori exposure, and a concomitant increase was seen in nuclear AIF levels up to 6 hours. A band corresponding to full-length Bid was seen in both the cytoplasmic and the nuclear fractions of controls, but not after H. pylori exposure. Active AIF staining was markedly increased in gastric mucosa from infected persons, compared to uninfected controls. Conclusion: H. pylori might trigger apoptosis in AGS cells via interaction with death receptors in the plasma membrane, leading to the cleavage of procaspase-8, release of cytochrome c and AIF from mitochondria, and activation of subsequent downstream apoptotic events, as reported previously for chlorophyllin. This is consistent with AIF activation that was found in the gastric mucosa of humans infected with H. pylori. Hence, the balance between apoptosis and proliferation in these cells may be altered in response to injury caused by H. pylori infection, leading to an increased risk of cancer.
KW - AIF
KW - Apoptosis
KW - Gastric cells
KW - H. pylori
KW - Mitochondria
UR - http://www.scopus.com/inward/record.url?scp=55949094326&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=55949094326&partnerID=8YFLogxK
U2 - 10.1111/j.1523-5378.2008.00646.x
DO - 10.1111/j.1523-5378.2008.00646.x
M3 - Article
C2 - 19166416
AN - SCOPUS:55949094326
SN - 1083-4389
VL - 13
SP - 506
EP - 517
JO - Helicobacter
JF - Helicobacter
IS - 6
ER -