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Abstract: PO0385

Untargeted Lipidomics Reveals the Potential Mechanism of Ferroptosis in HK-2 Cells Treated with Iohexol

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Zhou, Fangfang, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China, Ningbo, Zhejiang, China
  • Luo, Lianxin, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China, Ningbo, Zhejiang, China
  • Chen, Yixin, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China, Ningbo, Zhejiang, China
  • Lu, Yi, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China, Ningbo, Zhejiang, China
  • Luo, Qun, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China, Ningbo, Zhejiang, China
Background

The purpose of this study was to explore significantly different lipid markers that may be involved in the potential mechanism of ferroptosis in CIN.

Methods

Lipids were extracted from HK-2 cells (HK2-NC group) ,HK-2 cells treated with 100mg I/ml iohexol for 6 hours (HK2-I6 group) and HK-2 cells co-treated with iohexol and Ferrostatin-1(a potent and selective inhibitor of ferroptosis, Fer-1) (HK2-I6+FeI group) according to MTBE method. An Untargeted Relative uantitative lipidomics based on ultra-high performance liquid chromatography-Orbitrap mass spectrometry was used, combined with the lipids Search software (Thermo Scientific) .

Results

In our study, the Principal Component Analysis(PCA) and orthogonal partial least squares analysis(OPLS-DA) models were performed to explore the difference in lipid metabolites between the four groups. Both the PCA score plot and the OPLS-DA model revealed lipid differences, with a clear separation of metabolites between the HK2-I6 and HK2-NC groups , HK2-I6+FeI and HK2-I6 groups .
The heat map result showed 132 lipid variations of HK2-I6 group compared to the HK2-NC group, and 170 lipid variations of HK2-I6+FeI group compared to the HK2-I6 group. Among the varied lipid species (HK2-I6 group vs. HK2-NC group) , 35 out of 42 PC, 8 out of 10 PS, two out of three SM, and all the 6 LPC increased with statistical significance , while 38 out 39 TG, 16 out of 17 PE, and all the 9 Cer, 2 CerG2, 1 GM, 1 LPI, 2 PG decreased significantly. Among the varied lipid species (HK2-I6+FeI group vs. HK2-I6 group) , 35 out of 36 PE, 19 out of 36 PC, 3 out of 5 PS, and all the 50 TG, 15 SM, 5 PI, 5 PG, 6 Cer, 2 CerG1, 2 CerG2,2 CerG3, 2 LPE increased with statistical significance.
According to multivariate statistical analysis, PC(20:3/22:6), LPC(18:0), and PC(44:10), etc. were clearly increased in HK2-I6 group, while these lipid species were significantly decreased after Fer-1 treatment. Cer(d18:1/18:0), Cer(d18:2/24:1), and TG(18:0/18:1/22:2), etc. were clearly decreased in HK2-I6 group, while these lipid species were significantly increased after Fer-1 treatment.

Conclusion

This study revealed that increased PC, decreased PE and TG may involved in the potential mechanism of ferroptosis in the HK-2 cells treated with iohexol.