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Particulate matter induces ferroptosis by accumulating iron and dysregulating the antioxidant system

  • Minkyung Park (Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Young-Lai Cho (Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Yumin Choi (Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Jeong-Ki Min (MabTics Co. Ltd.) ;
  • Young-Jun Park (Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Sung-Jin Yoon (Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Dae-Soo Kim (Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Mi-Young Son (Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Su Wol Chung (School of Biological Sciences, University of Ulsan) ;
  • Heedoo Lee (Department of Biology and Chemistry, Changwon National University) ;
  • Seon-Jin Lee (Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
  • Received : 2022.09.13
  • Accepted : 2022.12.05
  • Published : 2023.02.28

Abstract

Particulate matter is an air pollutant composed of various components, and has adverse effects on the human body. Particulate matter is known to induce cell death by generating an imbalance in the antioxidant system; however, the underlying mechanism has not been elucidated. In the present study, we demonstrated the cytotoxic effects of the size and composition of particulate matter on small intestine cells. We found that particulate matter 2.5 (PM2.5) with extraction ion (EI) components (PM2.5 EI), is more cytotoxic than PM containing only polycyclic aromatic hydrocarbons (PAHs). Additionally, PM-induced cell death is characteristic of ferroptosis, and includes iron accumulation, lipid peroxidation, and reactive oxygen species (ROS) generation. Furthermore, ferroptosis inhibitor as liproxstatin-1 and iron-chelator as deferiprone attenuated cell mortality, lipid peroxidation, iron accumulation, and ROS production after PM2.5 EI treatment in human small intestinal cells. These results suggest that PM2.5 EI may increase ferroptotic-cell death by iron accumulation and ROS generation, and offer a potential therapeutic clue for inflammatory bowel diseases in human small intestinal cells.

Keywords

Acknowledgement

This research was funded by the KIST Institutional Program (2E31700- 22-P005), the KRIBB Research Initiative Program (KGM5322113), and the national research foundation (NRF-2014R1A6A1030318 and NRF-2021R1A2C1094382).

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