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Helicobacter. 2002 Dec;7(6):367-77.

Significance of the caspase family in Helicobacter pylori induced gastric epithelial apoptosis.

Author information

1
Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Germany.

Abstract

BACKGROUND AND AIMS:

H. pylori infection results in an increased epithelial apoptosis in gastritis and duodenal ulcer patients. We investigated the role and type of activation of caspases in H. pylori-induced apoptosis in gastric epithelial cells.

METHODS:

Differentiated human gastric cancer cells (AGS) and human gastric mucous cell primary cultures were incubated with H. pylori for 0.5-24 hours in RPMI 1640 medium, and the effects on cell viability, epithelial apoptosis, and activity of caspases were monitored. Apoptosis was analyzed by detection of DNA-fragments by Hoechst stain(R), DNA-laddering, and Histone-ELISA. Activities of caspases were determined in fluorogenic assays and by Western blotting. Cleavage of BID and release of cytochrome c were analyzed by Western blot. Significance of caspase activation was investigated by preincubation of gastric epithelial cells with cell permeable specific caspase inhibitors.

RESULTS:

Incubation of gastric epithelial cells with H. pylori caused a time and concentration dependent induction of DNA fragmentation (3-fold increase), cleavage of BID, release of cytochrome c and a concomittant sequential activation of caspase-9 (4-fold), caspase-8 (2-fold), caspase-6 (2-fold), and caspase-3 (6-fold). No effects on caspase-1 and -7 were observed. Activation of caspases preceded the induction of DNA fragmentation. Apoptosis could be inhibited by prior incubation with the inhibitors of caspase-3, -8, and -9, but not with that of caspase-1.

CONCLUSIONS:

Activation of certain caspases and activation of the mitochondrial apoptotic pathway are essential for H. pylori induced apoptosis in gastric epithelial cells.

[Indexed for MEDLINE]

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