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Decreased xCT activity in patients associated with Helicobacter pylori infection
Ling Wang1, Wen-Qun Li2, Fen Liu3
1Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China.
Insights
Helicobacter pylori (Hp) infection reduces cysteine/glutamate transporter (xCT) activity and glutamate levels in gastric ulcers. Targeting the microRNA/xCT pathway may offer a new treatment for Hp-related ulcers.
Area of Science:
- Gastroenterology
- Molecular Biology
- Pathophysiology
Background:
- Helicobacter pylori (Hp) infection is a common cause of gastritis and peptic ulcers.
- Cysteine/glutamate transporter (xCT) activity, crucial for glutamate regulation, decreases in animal models of Hp-induced gastric injury.
- The role of xCT activity in human Hp infection remains largely uncharacterized.
Purpose of the Study:
- To investigate the variations in xCT activity within the gastric mucosa of patients infected with Hp.
- To establish a clinical foundation for identifying novel therapeutic targets for Hp infection.
Main Methods:
- A cohort of 67 gastritis patients (23 Hp-positive, 44 Hp-negative) were analyzed.
- Gastric histology, urease tests, and Hp-colonization analysis were performed on antral biopsies.
- MicroRNA and xCT protein expression were assessed via immunohistochemical analysis; glutamate concentrations were measured.
Main Results:
- Hp-positive patients exhibited significantly lower xCT protein expression compared to Hp-negative individuals.
- A concurrent decrease in gastric juice glutamate concentration was observed in Hp-positive patients.
- Elevated expression of microRNAs known to downregulate xCT was found in Hp-positive patients.
Conclusions:
- Reduced xCT activity is implicated in the pathogenesis of gastric ulcers associated with Hp infection.
- The microRNA/xCT pathway presents a potential therapeutic target for managing Hp-infection-related gastric ulcers.
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.
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