Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Dec 5:13:1021655.
doi: 10.3389/fphar.2022.1021655. eCollection 2022.

Decreased xCT activity in patients associated with Helicobacter pylori infection

Ling Wang  1 , Wen-Qun Li  2 , Fen Liu  3 , Yuan-Jian Li  1 , Jie Du  1   4
Affiliations

Decreased xCT activity in patients associated with Helicobacter pylori infection

Ling Wang et al. Front Pharmacol. .

Abstract

Objective: In animals, Helicobacter pylori (Hp)-induced gastric injury is accompanied by a decrease in the activity of the cysteine/glutamate transporter (xCT), which regulates extracellular glutamate levels. However, the impact of xCT activity in patients with Hp infection remains unclear. This study aims to investigate variations of xCT activity in the gastric mucosa of patients with Hp infection and to provide a clinical basis for identifying targets related to Hp infection. Methods: Our study included a total of 67 patients with gastritis, which consisted of 44 Hp-negative and 23 Hp-positive peptic ulcer cases. The inclusion criteria used to select patients were as follows: gastric histology was determined with a gastroscope, antral biopsies were taken for urease tests, and pathology and culture were performed for analysis of Hp-colonization. The clinical characteristics of the patients were obtained, the expressions of microRNAs and xCT protein were detected using immune histochemical analysis, and the concentration of glutamate in their gastric secretion was determined. Results: The findings revealed that xCT expression was significantly lower in Hp-positive patients as compared to Hp-negative individuals, which was accompanied by a decrease in glutamate concentration in gastric juice. We also discovered a high expression of microRNAs that have been shown to negatively regulate xCT expression, in Hp-positive patients. Conclusion: Reduced xCT activity in patients may play an important role in gastric ulcers caused by Hp infection. Our findings suggest that the microRNA/xCT pathway could be a potential treatment target for Hp-infection-related ulcers.

Keywords: HP; gastric ulcer; glutamate; micrornas; xCT.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor JP declared a shared parent affiliation with the authors at the time of the review.

Figures

FIGURE 1
FIGURE 1
Tissue sections stained with hematoxylin-eosin were used to assess activity, inflammation, atrophy, and intestinal metaplasia. (A), Gastric tissue of Hp negative patients. (B), Gastric tissue of Hp positive patients.
FIGURE 2
FIGURE 2
Decreased xCT activity in Hp infection patients. (A). Immunohistochemistry staining for xCT antigen in gastro of Hp infection patients. (B). The concentration of glutamate in gastric secretion by HPLC. Data are means ± standard deviations. N = 23–44. Hp is short for Helicobacter pylori.
FIGURE 3
FIGURE 3
Identifying of miR-27a and miR-30b in gastro of patients using in situ hybridization. (A) MiR-27a expression in gastro of Hp negative and positive patients. (B) MiR-30b expression in gastro of Hp negative and positive patients.
See this image and copyright information in PMC

References

    1. AbdelAziz E. Y., Tadros M. G., Menze E. T. (2021). The effect of metformin on indomethacin-induced gastric ulcer: Involvement of nitric oxide/Rho kinase pathway. Eur. J. Pharmacol. 892, 173812. 10.1016/j.ejphar.2020.173812 - DOI - PubMed
    1. Chen S. H., Lei H. L., Huang L. R., Tsai L. H. (2001). Protective effect of excitatory amino acids on cold-restraint stress-induced gastric ulcers in mice: Role of cyclic nucleotides. Dig. Dis. Sci. 46, 2285–2291. 10.1023/a:1011991721640 - DOI - PubMed
    1. Cheng S. F., Li L., Wang L. M. (2015). miR-155 and miR-146b negatively regulates IL6 in Helicobacter pylori (cagA+) infected gastroduodenal ulcer. Eur. Rev. Med. Pharmacol. Sci. 19, 607–613. - PubMed
    1. de Brito B. B., da Silva F. A. F., Soares A. S., Pereira V. A., Santos M. L. C., Sampaio M. M., et al. (2019). Pathogenesis and clinical management of Helicobacter pylori gastric infection. World J. Gastroenterol. 25, 5578–5589. 10.3748/wjg.v25.i37.5578 - DOI - PMC - PubMed
    1. Drayton R. M., Dudziec E., Peter S., Bertz S., Hartmann A., Bryant H. E., et al. (2014). Reduced expression of miRNA-27a modulates cisplatin resistance in bladder cancer by targeting the cystine/glutamate exchanger SLC7A11. Clin. Cancer Res. 20, 1990–2000. 10.1158/1078-0432.CCR-13-2805 - DOI - PMC - PubMed

LinkOut - more resources