2. Academic Validation
  3. Pharmacological Inhibition of Phosphoglycerate Kinase 1 Reduces OxiDative Stress and Restores Impaired Autophagy in Experimental Acute Pancreatitis

Pharmacological Inhibition of Phosphoglycerate Kinase 1 Reduces OxiDative Stress and Restores Impaired Autophagy in Experimental Acute Pancreatitis

  • Inflammation. 2024 Oct 29. doi: 10.1007/s10753-024-02173-5.
Lin Chen # 1,  Zhihao Wang # 1,  Yuyan Zhang # 2,  Qingtian Zhu 1,  Guotao Lu 1,  Xiaowu Dong 1,  Jiajia Pan 2,  Keyan Wu 1,  Weijuan Gong 1,  Weiming Xiao 1,  Yanbing Ding 3,  Yanyan Zhang 4 5,  Yaodong Wang 6
Affiliations

Affiliations

  • 1 Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225000, China.
  • 2 Department of Intensive Care, Key Laboratory of Critical Care Medicine of Yangzhou, the Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225000, China.
  • 3 Pancreatic Center, Department of Gastroenterology, Yangzhou Key Laboratory of Pancreatic Disease, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225000, China. ybding@yzu.edu.cn.
  • 4 Medical College, Yangzhou University, Yangzhou, 225000, China. zyy@yzu.edu.cn.
  • 5 Testing Center, Yangzhou University, Yangzhou, 225000, China. zyy@yzu.edu.cn.
  • 6 Department of Gastroenterology, Kunshan Hospital of Traditional Chinese Medicine, Suzhou Key Laboratory of Integrated Traditional Chinese and Western Medicine of Digestive Diseases, Kunshan Affiliated Hospital of Yangzhou University, Kunshan, 215300, China. day.wang@live.cn.
  • # Contributed equally.
PMID: 39470963 DOI: 10.1007/s10753-024-02173-5
Abstract

Damage to pancreatic acinar cells (PAC) and intracellular metabolic disturbances play crucial roles in pancreatic necrosis during acute pancreatitis (AP). Phosphoglycerate kinase 1 (PGK1) is a crucial catalytic Enzyme in glycolysis. However, the impact of PGK1-involving glycolysis in regulating metabolic necrosis in AP is unclear. Transcriptome analysis of pancreatic tissues revealed significant changes in the glycolysis pathway and PGK1 which positively correlated with the inflammatory response and oxidative stress injury in AP mice. Furthermore, we observed a substantial increase in PGK1 expression in damaged PAC, positively correlating with PAC necrosis. Treatment with NG52, a specific PGK1 inhibitor, ameliorated pancreatic necrosis, inflammatory damage, and oxidative stress. Transcriptomic data before and after NG52 treatment along with the Programmed Cell Death database confirmed that NG52 protected against PAC damage by rescuing impaired Autophagy in AP. Additionally, the protective effect of NG52 was validated following pancreatic duct ligation. These findings underscore the involvement of PGK1 in AP pathogenesis, highlighting that PGK1 inhibition can mitigate AP-induced pancreatic necrosis, attenuate inflammatory and oxidative stress injury, and rescue impaired Autophagy. Thus, the study findings suggest a promising interventional target for pancreatic necrosis, offering novel strategies for therapeutic approaches to clinical AP.

Keywords

Acinar cell; Acute pancreatitis; NG52; Oxidative stress; Phosphoglycerate kinase 1.

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