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Helicobacter pylori Infection Activates the Akt–Mdm2–p53 Signaling Pathway in Gastric Epithelial Cells

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Abstract

Backgrounds and Aims

Although Helicobacter pylori is widely accepted as a causative factor of many gastric diseases, the signaling pathways affected by H. pylori and subsequent effects on cell apoptosis and proliferation remain unclear. Here, we investigated the molecular mechanisms mediating H. pylori infection in gastric epithelial cells.

Methods

Tissues from 160 patients with various gastric diseases with or without H. pylori infection were obtained and analyzed by immunohistochemistry for Akt, pAkt, Mdm2, p53, and Bax expression. In vitro, human gastric epithelial cells, GES-1, were incubated with H. pylori culture filtrates. Cell viability was measured by MTT assay. Apoptosis was evaluated by Annexin V/PI double staining followed by flow cytometry, DNA electrophoresis, and comet assay. mRNA and protein expression was assessed by RT-PCR and Western blot analysis.

Results

In patient tissues, H. pylori infection was associated with significantly elevated levels of pAkt in chronic nonatrophic gastritis (CNAG), Mdm2 in dysplasia, p53 in metaplastic atrophy (MA), and Bax in CNAG and MA. In vitro, H. pylori culture filtrates reduced GES-1 cell viability in a time- and dose-dependent manner, induced G0/G1 arrest, triggered apoptosis, and increased DNA fragmentation. Mdm2 and Bax mRNA expression and pAkt, Mdm2, p53, and Bax protein expression were significantly upregulated when treated with H. pylori culture filtrates. Akt inhibition by LY294002 decreased Mdm2 expression, upregulated p53, and enhanced H. pylori-induced growth inhibition of GES-1 cells.

Conclusions

These findings suggest that Akt–Mdm2–p53 signaling is involved in the molecular response of GES-1 cells to H. pylori infection.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Nos. 81160058, 30660067) and Natural Science Foundation of Jiangxi Province (No. 20114BAB205019).

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Authors and Affiliations

  1. Department of Gastroenterology, The First Affiliated Hospital, Nanchang University, Nanchang, 330006, Jiangxi, China

    Xu Shu, Zhen Yang, Zhong-Hua Li, Lian Chen, Xiao-Dong Zhou, Yong Xie & Nong-Hua Lu

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  1. Xu Shu
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  2. Zhen Yang
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  3. Zhong-Hua Li
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  4. Lian Chen
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  5. Xiao-Dong Zhou
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  7. Nong-Hua Lu
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Corresponding authors

Correspondence to Xu Shu or Nong-Hua Lu.

Additional information

Xu Shu and Zhen Yang have contributed equally to this work.

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Shu, X., Yang, Z., Li, ZH. et al. Helicobacter pylori Infection Activates the Akt–Mdm2–p53 Signaling Pathway in Gastric Epithelial Cells. Dig Dis Sci 60, 876–886 (2015). https://doi.org/10.1007/s10620-014-3470-2

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  • DOI: https://doi.org/10.1007/s10620-014-3470-2

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