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Kidney Week

Abstract: TH-PO109

Effect of Peroxidase Reductase 5 and Ferroptosis in Contrast-Induced AKI (CI-AKI)

Session Information

  • AKI: Mechanisms - I
    November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Zhou, Fangfang, Ningbo NO.2 Hospital, Ningbo, Zhejiang, China
  • Wang, Lailiang, Ningbo NO.2 Hospital, Ningbo, Zhejiang, China
  • Xu, Youjun, Ningbo NO.2 Hospital, Ningbo, Zhejiang, China
  • Qilin, Sheng, Ningbo NO.2 Hospital, Ningbo, Zhejiang, China
  • Zhang, Shuzhen, Ningbo NO.2 Hospital, Ningbo, Zhejiang, China
  • Zheng, Xingyue, Ningbo NO.2 Hospital, Ningbo, Zhejiang, China
  • Luo, Qun, Ningbo NO.2 Hospital, Ningbo, Zhejiang, China
Background

Our previous study found the expression of urinary peroxidase reductase 5 (PRDX5) decreased significantly in CI-AKI patients by proteomics,and ferroptosis was involved in CI-AKI. The aim was to identify PRDX5 involved in the mechanism of ferroptosis in CI-AKI.

Methods

Human renal tubule epithelial cells (HK-2) were cultured and divided into control group, CI-AKI group (HK-2 cells were added 200 mg I/ml iodohexol for 12h), CI-AKI+ FeI group (HK-2 cells were added 200 mg I/ml iodohexol and ferroptosis inhibitor,10μmol/L for 12h), PRDX5 overexpression group (PRDX5 overexpression plasmid was constructed), PRDX5 overexpression +CI-AKI group (PRDX5 overexpression HK-2 cells were added 200 mg I/ml iodohexol for 12h). The cell activity was determined by MTT assay. The expressions of ferroptosis related protein GPX4, SLC7A11 and ACSL4 were detected by western blot. Iron Assay Kit was used to measure intracellular iron. Mitochondrial ROS levels were detected by DCFDA/H2DCFDA fluorescent probe.

Results

Compared with control group, the cell proliferation rate of CI-AKI group slowed down significantly, while that of CI-AKI+ FeI group was increased, compared with CI-AKI group, (P<0.05). In terms of ferroptosis mechanism, compared with control group, the protein content of ACSL4, GPX4 and SLC7A11 in HK-2 cells in CI-AKI group was significantly increased (p<0.05), the protein contents of GPx4 and SLC7A11 were significantly decreased (p<0.05), the iron content was significantly increased (p<0.05), and the mitochondrial ROS level was significantly increased (p<0.05). After adding ferroptosis inhibitor, the above indexes were relieved (p<0.05).
The expression of PRDX5 mRNA and protein in CI-AKI group was significantly decreased compared with control group (p<0.05), and that in PRDX5 overexpression group was significantly increased (p<0.05). Compared with CI-AKI group, PRDX5 overexpression+CI-AKI group increased cell proliferation rate (P<0.05). Compared with CI-AKI group, the expression of ferroptosis related protein ACSL4, GPX4 and SLC7A11 were significantly decreased (p<0.05), iron content was significantly decreased (p<0.05), and mitochondrial ROS level was significantly decreased (p<0.05) after overexpression of PRDX5.

Conclusion

Ferroptosis is involved in CI-AKI. PRDX5 has a protective effect on the mechanism of ferroptosis in CI-AKI.