Glutathione peroxidase 7 protects against oxidative DNA damage in oesophageal cells
View abstract on PubMed
Summary
This summary is machine-generated.Glutathione peroxidase 7 (GPX7) protects oesophageal cells from oxidative stress and DNA damage caused by acid and bile reflux. Loss of GPX7 function promotes Barrett's oesophagus and oesophageal adenocarcinoma (OAC) development.
Area Of Science
- Gastroenterology
- Molecular Biology
- Oncology
Background
- Oesophageal mucosa exposure to gastric acid and bile acids generates reactive oxygen species (ROS).
- ROS accumulation is a known risk factor for Barrett's oesophagus and oesophageal adenocarcinoma (OAC).
- Glutathione peroxidase 7 (GPX7) is frequently silenced in OAC, suggesting a role in disease progression.
Purpose Of The Study
- To investigate the functions of glutathione peroxidase 7 (GPX7).
- To determine GPX7's capacity in regulating ROS and associated oxidative DNA damage.
- To assess GPX7's role in the context of Barrett's oesophagus and OAC.
Main Methods
- Utilized in-vitro cell models including immortalised Barrett's oesophagus cells (BAR-T, CP-A) and oesophageal squamous epithelial cells (HET1A).
- Assessed GPX activity, hydrogen peroxide (H2O2) neutralization, ROS levels, oxidative DNA damage (8-oxoguanine, phospho-H2A.X), apoptosis (Annexin V), and signalling pathways (phospho-JNK, phospho-p38).
- Employed quantitative real-time PCR and western blot assays to evaluate gene and protein expression, including GPX7 reconstitution and knockdown.
Main Results
- Recombinant GPX7 demonstrated H2O2-neutralizing capacity independent of glutathione.
- GPX7 expression in Barrett's cells conferred resistance to H2O2-induced oxidative stress and reduced ROS, DNA damage, and apoptosis under acidic bile acid conditions.
- GPX7 knockdown in HET1A cells increased susceptibility to oxidative stress, DNA damage, and apoptosis induced by acidic bile acids.
Conclusions
- GPX7 plays a crucial protective role against ROS and oxidative DNA damage in oesophageal cells.
- GPX7 dysfunction contributes to the pathogenesis of Barrett's oesophagus and oesophageal adenocarcinoma (OAC).
- Restoring GPX7 function may represent a therapeutic strategy for preventing OAC progression.