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Particulate matter induces ferroptosis by accumulating iron and dysregulating the antioxidant system
Minkyung Park1,2 (Graduate student), Young-Lai Cho1 (Research Fellow), Yumin Choi1,2 (Graduate student), Jeong-Ki Min3 (Principal Researcher), Young-Jun Park1,2 (Principal Researcher), Sung-Jin Yoon1,2 (Senior Researcher), Dae-Soo Kim1,2 (Principal Researcher), Mi-Young Son1,2 (Principal Researcher), Su Wol Chung4 (Professor), Heedoo Lee5 (Professor), Seon-Jin Lee 1,2,* (Principal Researcher)
1Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology,
2Department of Functional Genomics, University of Science and Technology (UST),
3MabTics, Co. Ltd,
4School of Biological Sciences, University of Ulsan,
5Department of Biology and Chemistry, Changwon National University
Abstract
Particulate matter is an air pollutant composed of various components that 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. Furthemore, ferroptosis inhibitor as liprostatin-1 and iron-chealator as deferiprone attenuated cell mortality, lipid peroxidation, iron accumulation, 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 be a potential therapeutic clue for inflammatory bowel diseases in human small intestinal cells.
Abstract, Accepted Manuscript(in press) [Submitted on September 13, 2022, Accepted on December 5, 2022]
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