DOI QR코드

DOI QR Code

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))
  • 투고 : 2022.09.13
  • 심사 : 2022.12.05
  • 발행 : 2023.02.28

초록

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.

키워드

과제정보

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).

참고문헌

  1. Brunekreef B and Holgate ST (2002) Air pollution and health. Lancet 360, 1233-1242 https://doi.org/10.1016/S0140-6736(02)11274-8
  2. Cheng H, Gong W, Wang Z et al (2014) Ionic composition of submicron particles (PM1.0) during the long-lasting haze period in January 2013 in Wuhan, central China. J Environ Sci 26, 810-817 https://doi.org/10.1016/S1001-0742(13)60503-3
  3. Frey A, Ramaker K, Rockendorf N et al (2019) Fate and translocation of (nano) particulate matter in the gastrointestinal tract; in Biological Responses to Nanoscale Particles, Gehr P and Zellner R (eds.), 281-327, Nanosci Technol, Springer, USA
  4. Beamish LA, Osornio-Vargas AR and Wine E (2011) Air pollution: an environmental factor contributing to intestinal disease. J Crohn's Colitis 5, 279-286 https://doi.org/10.1016/j.crohns.2011.02.017
  5. Wang Y, Zhong Y, Liao J and Wang G (2021) PM2.5-related cell death patterns. Int J Med Sci 18, 1024
  6. Michael S, Montag M and Dott W (2013) Pro-inflammatory effects and oxidative stress in lung macrophages and epithelial cells induced by ambient particulate matter. Environ Pollut 183, 19-29 https://doi.org/10.1016/j.envpol.2013.01.026
  7. Su LJ, Zhang JH, Gomez H et al (2019) Reactive oxygen species-induced lipid peroxidation in apoptosis, autophagy, and ferroptosis. Oxid Med Cell Longev 2019, 5080843
  8. Dixon SJ, Lemberg KM, Lamprecht MR et al (2012) Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149, 1060-1072 https://doi.org/10.1016/j.cell.2012.03.042
  9. Xie Y, Hou W, Song X et al (2016) Ferroptosis: process and function. Cell Death Differ 23, 369-379 https://doi.org/10.1038/cdd.2015.158
  10. Chen X, Li J, Kang R, Klionsky DJ and Tang D (2021) Ferroptosis: machinery and regulation. Autophagy 17, 2054-2081 https://doi.org/10.1080/15548627.2020.1810918
  11. Woodby B, Schiavone ML, Pambianchi E et al (2020) Particulate matter decreases intestinal barrier-associated proteins levels in 3D human intestinal model. Int J Environ Res Public Health 17, 3234
  12. Conrad M, Kagan VE, Bayir H et al (2018) Regulation of lipid peroxidation and ferroptosis in diverse species. Genes Dev 32, 602-619 https://doi.org/10.1101/gad.314674.118
  13. Wang Y and Tang M (2019) PM2.5 induces ferroptosis in human endothelial cells through iron overload and redox imbalance. Environ Pollut 254, 112937
  14. Kwon MY, Park EH, Lee SJ and Chung SW (2015) Heme oxygenase-1 accelerates erastin-induced ferroptotic cell death. Oncotarget 6, 24393-24403 https://doi.org/10.18632/oncotarget.5162
  15. Towers CG, Wodetzki D and Thorburn A (2020) Autophagy and cancer: modulation of cell death pathways and cancer cell adaptations. J Cell Biol 219, e201909033
  16. Liu Y, Zhao D, Peng W et al (2021) Atmospheric PM2.5 blocking up autophagic flux in HUVECs via inhibiting Sntaxin-17 and LAMP2. Ecotoxicol Environ Saf 208, 111450
  17. Charoud-Got J, Emma G, Seghers J et al (2017) Preparation of a PM2.5-like reference material in sufficient quantities for accurate monitoring of anions and cations in fine atmospheric dust. Anal Bioanal Chem 409, 7121-7131  https://doi.org/10.1007/s00216-017-0670-6