1. Academic Validation
  2. Cr(VI) induces ferroptosis in DF-1 cells by simultaneously perturbing iron homeostasis of ferritinophagy and mitophagy

Cr(VI) induces ferroptosis in DF-1 cells by simultaneously perturbing iron homeostasis of ferritinophagy and mitophagy

  • Sci Total Environ. 2024 Mar 19:925:171818. doi: 10.1016/j.scitotenv.2024.171818.
Kaimin Song 1 Xiaoting Liu 2 Huiling Xu 1 Muzi Li 1 Qi Zheng 1 Changxi Qi 1 Xiaozhou Wang 2 Yongxia Liu 1 Pimiao Zheng 3 Jianzhu Liu 4
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Shandong Agricultural University, Tai'an, Shandong 271018, China.
  • 2 Research Center for Animal Disease Control Engineering, Shandong Agricultural University, Tai'an, Shandong 271018, China.
  • 3 Research Center for Animal Disease Control Engineering, Shandong Agricultural University, Tai'an, Shandong 271018, China. Electronic address: zhengpm@sdau.edu.cn.
  • 4 College of Veterinary Medicine, Shandong Agricultural University, Tai'an, Shandong 271018, China. Electronic address: liujz@sdau.edu.cn.
Abstract

Hexavalent chromium [Cr(VI)] is an environmental pollutant known for its strong oxidizing and carcinogenic effects. However, its potential to induce Ferroptosis in poultry remains poorly understood. This study aims to investigate the induction of Ferroptosis by Cr(VI) in DF-1 cells and elucidate the underlying mechanisms. DF-1 cells exposed to Cr(VI) showed increased lipid Reactive Oxygen Species and changes in Ferroptosis marker genes (decreased expression of GPX4 and increased expression of COX2). Notably, the addition of the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1) can reverse this effect. During the cell death process, Cr(VI) induced ferritinophagy, disrupting iron homeostasis and releasing labile iron ions. We predicted by docking that these iron ions would bind to mitochondrial membrane proteins through virtual docking. This binding was validated through colocalization analysis. In addition, Cr(VI) caused Mitophagy, which releases additional ferrous ions. Therefore, Cr(VI) can induce the simultaneous release of ferrous ions through these pathways, thereby exacerbating lipid peroxidation and ultimately triggering Ferroptosis in DF-1 cells. This study demonstrates that Cr(VI) can induce Ferroptosis in DF-1 cells by disrupting intracellular iron homeostasis and providing valuable insights into the toxic effects of Cr(VI) in poultry and potentially other organisms.

Keywords

DF-1 cells; Ferritinophagy; Ferroptosis; Hexavalent chromium; Labile iron.

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