Disturbance of apoptosis and DNA synthesis by Helicobacter pylori infection of hepatocytes.
We evaluated the effects of infection of hepatocytes with the well-characterized Helicobacter species, H. pylori. Cell number doubled during each 24 h period in mock cultures or following infection with H. pylori 401C (CagA-, VacA-, BabA-, OipA-) (P < 0.05). In contrast, infection with the more virulent H. pylori NCTC11637 (CagA+, VacA+, BabA+, OipA+) resulted in cell arrest (P < 0.05). Furthermore, NCTC11637 activated caspase-3 and increased DNA fragmentation 6.1 +/- 1.2 fold (P < 0.01) and the number of apoptotic bodies 9.4 +/- 3.5 fold (P < 0.01) compared to controls. The effect was greater than with the less virulent strain 401C (3.8 +/- 0.6 fold and 3.9 +/- 1.7, respectively, P < 0.05). Strain NCTC11637 at low concentrations increased cellular DNA synthesis 139 +/- 6% (P < 0.05) but decreased it to 16 +/- 7% (P < 0.01) at high concentrations. In contrast, strain 401C increased DNA synthesis 155 +/- 14% of controls (P < 0.05) at high concentrations. The presence of intracellular NCTC11637 within hepatocytes increased DNA fragmentation 3.0 +/- 0.4 fold (P < 0.01) greater than in controls. H. pylori infection resulted in strain-species-dependent effects on hepatocytes, and virulent strain caused cell arrest and apoptosis of infected hepatocytes.
Ito
Kyoko
K
Department of Medicine, GI Section, Michael E DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, 2002 Holcombe Blvd. 3A-320, Houston, TX 77030, USA.
Yamaoka
Yoshio
Y
Yoffe
Boris
B
Graham
David Y
DY
D017209:Apoptosis / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004247:DNA / Q000378:metabolism*; D053938:DNA Fragmentation; D016481:Helicobacter Infections / Q000378:metabolism* / Q000503:physiopathology*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D022781:Hepatocytes / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D014774:Virulence
D004247:DNA; D053148:Caspase 3