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AMPK activation alleviated dextran sulfate sodium-induced colitis by inhibiting ferroptosis. | LitMetric

AI Article Synopsis

  • Ferroptosis is a newly identified form of cell death occurring in the intestinal epithelial cells of patients with ulcerative colitis (UC), and this study explores its link to AMPK.
  • Using gene expression data and both human and animal models, researchers assessed ferroptosis markers and its effects on inflammation, iron levels, and lipid peroxidation.
  • Findings showed reduced GPX4 and FTH1 levels in UC patients, increased iron and lipid damage in mice, and that activating AMPK with metformin reduced ferroptosis and improved symptoms in a colitis mouse model, suggesting a potential treatment avenue for UC.

Article Abstract

Objectives: Ferroptosis is a newly discovered cell death mode that has been confirmed to occur in the intestinal epithelial cells in ulcerative colitis (UC). In this study we aimed to elucidate the mechanism of ferroptosis and its association with adenosine monophosphate-activated protein kinase (AMPK) in UC.

Methods: Gene expression profiles of colonic mucosa (GSE87473) were downloaded. Both human colonic samples and dextran sodium sulfate (DSS)-induced colitis murine model were used. The molecular markers of ferroptosis were detected using western blot and immunohistochemistry. Symptoms, iron abundance, and lipid peroxidation level of the mouse model were measured to evaluate the role of AMPK activation in ferroptosis.

Results: Both gene and protein expressions of GPX4 and FTH1 were decreased in UC patients compared with the healthy controls. An increased iron abundance and lipid peroxidation level in colon tissues and damaged mitochondria were found in DSS-induced colitis. AMPK expression was decreased in UC patients and correlated with FTH1 and GPX4. Activation of AMPK with metformin inhibited ferroptosis in the colon, improved symptoms, and prolonged the lifespan in DSS-induced colitis mice.

Conclusions: Ferroptosis can be observed in colonic tissues in UC. AMPK activation inhibits ferroptosis in murine colitis model, which may act as a potential target for the treatment of colitis.

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Source
http://dx.doi.org/10.1111/1751-2980.13176DOI Listing

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