Fatal COVID-19 pulmonary disease involves ferroptosis.

Autor: Qiu B; Department of Chemistry, Columbia University, New York, NY, 10027, USA., Zandkarimi F; Department of Chemistry, Columbia University, New York, NY, 10027, USA.; Mass Spectrometry Core Facility, Department of Chemistry, Columbia University, New York, NY, 10027, USA., Saqi A; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, 10032, USA., Castagna C; Institute of Comparative Medicine, Columbia University Irving Medical Center, New York, NY, 10032, USA., Tan H; Department of Chemistry, Columbia University, New York, NY, 10027, USA., Sekulic M; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, 10032, USA., Miorin L; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Global Health Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Hibshoosh H; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, 10032, USA., Toyokuni S; Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.; Center for Low-temperature Plasma Sciences, Nagoya University, Furo-Cho, Chikusa-ku, Nagoya, 464-8603, Japan., Uchida K; Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan., Stockwell BR; Department of Chemistry, Columbia University, New York, NY, 10027, USA. bstockwell@columbia.edu.; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, 10032, USA. bstockwell@columbia.edu.; Department of Biological Sciences, Columbia University, New York, NY, 10027, USA. bstockwell@columbia.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 May 20; Vol. 15 (1), pp. 3816. Date of Electronic Publication: 2024 May 20.
DOI: 10.1038/s41467-024-48055-0
Abstrakt: SARS-CoV-2 infection causes severe pulmonary manifestations, with poorly understood mechanisms and limited treatment options. Hyperferritinemia and disrupted lung iron homeostasis in COVID-19 patients imply that ferroptosis, an iron-dependent cell death, may occur. Immunostaining and lipidomic analysis in COVID-19 lung autopsies reveal increases in ferroptosis markers, including transferrin receptor 1 and malondialdehyde accumulation in fatal cases. COVID-19 lungs display dysregulation of lipids involved in metabolism and ferroptosis. We find increased ferritin light chain associated with severe COVID-19 lung pathology. Iron overload promotes ferroptosis in both primary cells and cancerous lung epithelial cells. In addition, ferroptosis markers strongly correlate with lung injury severity in a COVID-19 lung disease model using male Syrian hamsters. These results reveal a role for ferroptosis in COVID-19 pulmonary disease; pharmacological ferroptosis inhibition may serve as an adjuvant therapy to prevent lung damage during SARS-CoV-2 infection.
(© 2024. The Author(s).)
Databáze: MEDLINE
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