2. Academic Validation
  3. Nrf2 ameliorates defective autophagic processes and thereby inhibits ferroptosis in acute pancreatitis by suppressing Beclin1-Slc7a11 complex formation

Nrf2 ameliorates defective autophagic processes and thereby inhibits ferroptosis in acute pancreatitis by suppressing Beclin1-Slc7a11 complex formation

  • Free Radic Biol Med. 2025 Feb 11:S0891-5849(25)00085-1. doi: 10.1016/j.freeradbiomed.2025.02.011.
Jie Li 1,  Yu-Chen Jia 2,  Haoyu Zhang 3,  Zheng Wang 4,  Yixuan Ding 5,  Feng Cao 6,  Gang Wang 7,  Fei Li 8
Affiliations

Affiliations

  • 1 Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China; Clinical Center for Acute Pancreatitis, Capital Medical University, Beijing, China. Electronic address: 754753230@qq.com.
  • 2 Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China; Clinical Center for Acute Pancreatitis, Capital Medical University, Beijing, China. Electronic address: 2927450757@qq.com.
  • 3 Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China; Clinical Center for Acute Pancreatitis, Capital Medical University, Beijing, China. Electronic address: zhy199848@163.com.
  • 4 Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China; Clinical Center for Acute Pancreatitis, Capital Medical University, Beijing, China. Electronic address: wangzheng@mail.ccmu.edu.cn.
  • 5 Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China; Clinical Center for Acute Pancreatitis, Capital Medical University, Beijing, China. Electronic address: dingyixuan@xwhosp.org.
  • 6 Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China; Clinical Center for Acute Pancreatitis, Capital Medical University, Beijing, China. Electronic address: caofeng1221@163.com.
  • 7 Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China. Electronic address: wgilu79@163.com.
  • 8 Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China; Clinical Center for Acute Pancreatitis, Capital Medical University, Beijing, China. Electronic address: feili36@ccmu.edu.cn.
PMID: 39947493 DOI: 10.1016/j.freeradbiomed.2025.02.011
Abstract

Ferroptosis is a mode of programmed cell death that plays an important role in an increasing number of diseases. Recently, Ferroptosis was found to be involved in the pathology of acute pancreatitis (AP). We determined that nuclear factor erythroid 2-related factor 2 (Nrf2) plays a pivotal role in the Ferroptosis process in AP. By inhibiting Nrf2 expression, the death of acinar cells in AP can be increased. Therefore, to help treat AP to a certain extent, we analyzed the effects of astaxanthin and found that it can activate Nrf2 and reduce the pathological process of AP. The activation of Nrf2 improves defective Autophagy in AP and inhibits Ferroptosis in acinar cells. Specifically, Nrf2 can promote the expression of Gpx4 and ferritin, and can inhibit the formation of Beclin-Slc7a11 complex by improving Autophagy, thereby increasing the membrane expression of Slc7a11. Slc7a11/Gpx4 is an important anti-ferroptosis pathway; Slc7a11 can promote the synthesis of glutathione, while Gpx4 can utilize glutathione to exert antioxidative effects. Thus, we demonstrated that Nrf2 activation not only ameliorated defective Autophagy at the time of AP but also promoted membrane expression of Slc7a11 to inhibit Ferroptosis in acinar cells, thereby alleviating AP.

Keywords

Nrf2; acute pancreatitis; autophagy; ferroptosis; inflammation.

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