Compound 13, an α1-selective small molecule activator of AMPK, inhibits  Helicobacter pylori -induced oxidative stresses and gastric epithelial cell apoptosis

ABSTRACT Recent evidence suggests that immune-mediated gastric epithelial cell apoptosis through Fas-Fas ligand interactions participates in Helicobacter pylori disease pathogenesis. To define the role of Fas signaling in vivo, H. pylori strain SS1 infection in C57BL/6 mice was compared to that in mice deficient in the Fas ligand (gld). gld mice had a degree of gastritis similar to that of C57BL/6 mice after 6 weeks (gastritis score, 5.2 ± 0.6 [mean ± standard error] versus 3.5 ± 0.8) and 12 weeks (4.0 ± 0.7 versus 3.4 ± 0.5) of infection. Bacterial colonization was comparable in each group of mice at 12 weeks of infection (2.1 ± 0.3 versus 1.6 ± 0.3 for gld and C57BL/6, respectively; the difference is not significant). Sixty-seven percent of H. pylori-infected gld mice displayed atrophic changes in the gastric mucosa, compared with 37% of infected C57BL/6 mice, at 12 weeks. In addition, atrophic changes were more severe in H. pylori-infected gld mice (P < 0.05). Splenocytes isolated from H. pylori-infected C57BL/6 mice had a twofold increase in production of the Th1 cytokine gamma interferon (IFN-γ) in response to H. pylori antigens at both 6 and 12 weeks compared to controls (143 ± 65 versus 69 ±26 pg/ml and 336 ± 73 versus 172 ± 60, respectively). In contrast, there was a lack of detectable IFN-γ in gld mice infected with the bacterium. H. pylori-infected C57BL/6 mice had increased epithelial cell apoptosis compared with sham-infected C57BL/6 mice (35.0 ± 8.9 versus 12.3 ± 6.9; P < 0.05). Epithelial cell apoptosis did not differ between H. pylori-infected and control gld mice (5.2 ± 1.6 versus 6.5 ± 2.9 [not significant]). These data demonstrate that mice with mutations in the Fas ligand develop more severe premalignant mucosal changes in response to infection with H. pylori in association with both an impaired gastric epithelial cell apoptotic response and IFN-γ production. The Fas death pathway modulates disease pathophysiology following murine infection with H. pylori. Deregulation of the Fas pathway could be involved in the transition from gastritis to gastric cancers during H. pylori infection.

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Tu1278 - Puma-Mediated Gastric Epithelial Cell Apoptosis Promotes Helicobacter Pylori Dependent Gastritis

Gastroenterology ◽

10.1016/s0016-5085(18)33104-4 ◽

2018 ◽

Vol 154 (6) ◽

pp. S-922-S-923

Author(s):

Jing Sun ◽

Yini Dang ◽

Yifeng Zhang ◽

Xiaoying Zhou ◽

Yi Zhang ◽

...

Keyword(s):

Helicobacter Pylori ◽

Epithelial Cell ◽

Cell Apoptosis ◽

Gastric Epithelial Cell ◽

Epithelial Cell Apoptosis

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OC-049 Bak expression regulatesHelicobacter felis-induced gastric epithelial cell apoptosis and the extent of gastric atrophy in vivo

Gut ◽

10.1136/gut.2009.208959w ◽

2010 ◽

Vol 59 (Suppl 1) ◽

pp. A20.2-A20

Author(s):

A A Abuderman ◽

A Varro ◽

D M Pritchard

Keyword(s):

Epithelial Cell ◽

Cell Apoptosis ◽

Gastric Atrophy ◽

Gastric Epithelial Cell ◽

Epithelial Cell Apoptosis

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PUMA-mediated epithelial cell apoptosis promotes Helicobacter pylori infection-mediated gastritis

Cell Death and Disease ◽

10.1038/s41419-020-2339-x ◽

2020 ◽

Vol 11 (2) ◽

Cited By ~ 1

Author(s):

Yini Dang ◽

Yifeng Zhang ◽

Lingyan Xu ◽

Xiaoying Zhou ◽

Yanhong Gu ◽

...

Keyword(s):

Helicobacter Pylori ◽

Epithelial Cell ◽

Cell Apoptosis ◽

Helicobacter Pylori Infection ◽

Epithelial Cell Apoptosis

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Su1034 – Rebamipide Reduces Gastric Epithelial Cell Apoptosis Through ERS/Nf-κB/Autophagy Pathway

Gastroenterology ◽

10.1016/s0016-5085(19)38088-6 ◽

2019 ◽

Vol 156 (6) ◽

pp. S-490

Author(s):

Jingwen Zhao ◽

Mengjing Liu ◽

Qijin He ◽

Ya wang ◽

Xin Chen ◽

...

Keyword(s):

Epithelial Cell ◽

Cell Apoptosis ◽

Gastric Epithelial Cell ◽

Epithelial Cell Apoptosis ◽

Autophagy Pathway

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Effect of Inhibition of Extracellular Signal-Regulated Kinase 1 and 2 Pathway on Apoptosis and bcl-2 Expression in Helicobacter pylori-Infected AGS Cells

Infection and Immunity ◽

10.1128/iai.71.2.830-837.2003 ◽

2003 ◽

Vol 71 (2) ◽

pp. 830-837 ◽

Cited By ~ 41

Author(s):

Il Ju Choi ◽

Joo Sung Kim ◽

Jung Mogg Kim ◽

Hyun Chae Jung ◽

In Sung Song

Keyword(s):

Gene Expression ◽

Helicobacter Pylori ◽

Epithelial Cell ◽

Cell Apoptosis ◽

Ags Cells ◽

Extracellular Signal Regulated Kinase ◽

Extracellular Signal ◽

Epithelial Cell Apoptosis ◽

H Pylori ◽

Induced Apoptosis

ABSTRACT Helicobacter pylori induces activation of mitogen-activated protein kinases (MAPKs). However, its effect on H. pylori-induced apoptosis has not been evaluated. Thus, we examined whether H. pylori-induced extracellular signal-regulated kinase 1 and 2 (ERK1/2) and p38 MAPK activation affects gastric epithelial cell apoptosis and bcl-2 family gene expression, especially in relation to the cagA status of an H. pylori strain. In flow cytometric and oligonucleosome-bound DNA enzyme-linked immunosorbent assay analyses, infection with cagA + H. pylori strains induced gastric cancer cell apoptosis in AGS cells more prominently than infection with cagA mutants. Activation of ERK1/2 and p38 MAPKs was also more prominent in cagA + strains. Pretreatment with a MEK inhibitor (PD98059) inhibited ERK1/2 activation and increased H. pylori-induced apoptosis significantly. This increased apoptosis was accompanied by decreased antiapoptotic bcl-2 mRNA expression among bcl-2-related genes (bcl-2, bax, bak, mcl-1, and bcl-XL/S ), and the effect was also more prominent in the cagA + strains. However, the alteration of bcl-2 gene expression was not accompanied by protein level changes. Inhibition of p38 using specific inhibitor SB203580 decreased H. pylori-induced apoptosis but resulted in little alteration of bcl-2-related gene expression. In conclusion, H. pylori-induced ERK1/2 activation, especially by the cagA + H. pylori strain, may play a protective role against gastric epithelial cell apoptosis partially through maintenance of bcl-2 gene expression.

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