CHAC1 overexpression in human gastric parietal cells with Helicobacter pylori infection in the secretory canaliculi

Abstract

Background Cation transport regulator 1 (CHAC1), a newly discovered enzyme that degrades glutathione, is induced in Helicobacter pylori ( H. pylori )‐infected gastric epithelial cells in culture. The CHAC1‐induced decrease in glutathione leads to an accumulation of reactive oxygen species and somatic mutations in TP53 . We evaluated the possible correlation between H. pylori infection and CHAC1 expression in human gastric mucosa. Materials and Methods Both fresh‐frozen and formalin‐fixed paraffin‐embedded tissue samples of gastric mucosa with or without H. pylori infection were obtained from 41 esophageal cancer patients that underwent esophago‐gastrectomy. Fresh samples were used for real‐time polymerase chain reaction for H. pylori DNA and CHAC1 mRNA, and formalin‐fixed samples were used for immunohistochemistry with anti‐CHAC1 and anti‐ H. pylori monoclonal antibodies. Double‐enzyme or fluorescence immunohistochemistry and immuno‐electron microscopy were used for further analysis. Results Significant CHAC1 overexpression was detected in H. pylori ‐infected parietal cells that expressed the human proton pump/H,K‐ATPase α subunit, whereas a constitutively low level of CHAC1 mRNA expression was observed in the other samples regardless of the H. pylori infection status, reflecting the weak CHAC1 expression detected by immunohistochemistry in the fundic‐gland areas. Immuno‐electron microscopy revealed intact H. pylori cells in the secretory canaliculi of infected parietal cells. Some parietal cells exhibited positive nuclear signals for Ki67 in the neck zone of the gastric fundic‐gland mucosa with H. pylori infection. Conclusion Cation transport regulator 1 overexpression in H. pylori ‐infected parietal cells may cause the H. pylori ‐induced somatic mutations that contribute to the development of gastric cancer.

Ferroptosis‐related gene NOX4, CHAC1 and HIF1A are valid biomarkers for stomach adenocarcinoma

“…Increased expression of CHAC1 can lead to glutathione depletion and an imbalance in cellular REDOX levels 19 . Tomohisa et al 20 found that overexpression of CHAC1 may contribute to the development of stomach cancer in Helicobacter pylori ‐infected parietal cells. NADPH oxidases (nicotinamide adenine dinucleotide phosphate oxidase, NOXs) are the major source of ROS in cancer cells 21 .…”

Construction of a Ferroptosis-Related Gene Signature for Predicting Survival and Immune Microenvironment in Melanoma Patients

“…33 CHAC1 was discovered to digest glutathione, converting it to 5-oxoproline and Cys-Glydipeptide, lowering intracellular GSH levels. 34 Increased expression of CHAC1 in breast and ovarian cancer patients may mean a higher risk of cancer recurrence. 35 Until now, the mechanism of ALOX5 and CHAC1 in SKCM has remained a mystery.…”

Identification of novel antioxidant gene signature to predict the prognosis of patients with gastric cancer

“…Our results also indicated the protective role of CHAC1 and showed significant predictive value. Contradictorily, some scholars found the overexpression of CHAC1 in H. pylori-infected parietal cells could increase the risk of GC [45], but overall, there are few studies and direct evidence illustrating the relationship between CHAC1 and GC. As analyzed above, these two key antioxidant-related enzymes act as important parts in the growth and proliferation of GC and show prognostic value in GC patients.…”