Pseudomonas aeruginosa utilizes host polyunsaturated phosphatidylethanolamines to trigger theft-ferroptosis in bronchial epithelium
| Autor: | Cody J. Freedman, Jennifer M. Bomberger, Becca A. Flitter, Yohei Doi, Janet S. Lee, Erkan Bayir, Gaowei Mao, Joseph M. Pilewski, Indira H. Shrivastava, Matthew R. Parsek, Valerian E. Kagan, Joel S. Greenberger, Abiola F. Ogunsola, Hong Wang, Haider H. Dar, Rama K. Mallampalli, Theodore R. Holman, Tamil S. Anthonymuthu, Simon C. Watkins, Karolina Mikulska-Ruminska, Yulia Y. Tyurina, Jordan R. Gaston, Claudette M. St. Croix, Hsiu Chi Ting, Ivet Bahar, James Krieger, Catherine R. Armbruster, Alexandr A. Kapralov, Hülya Bayır, Vladimir A. Tyurin |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cystic Fibrosis Apoptosis Respiratory Mucosa medicine.disease_cause Cystic fibrosis Cell Line Microbiology 03 medical and health sciences Lipoxygenase 0302 clinical medicine medicine Humans Pseudomonas Infections Respiratory Tract Infections Liver injury chemistry.chemical_classification Kidney biology Respiratory tract infections Pseudomonas aeruginosa Phosphatidylethanolamines Epithelial Cells General Medicine medicine.disease biology.organism_classification 030104 developmental biology Enzyme medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis biology.protein Bacteria Research Article |
| Zdroj: | Journal of Clinical Investigation. 128:4639-4653 |
| ISSN: | 1558-8238 0021-9738 |
| Popis: | Ferroptosis is a death program executed via selective oxidation of arachidonic acid–phosphatidylethanolamines (AA-PE) by 15-lipoxygenases. In mammalian cells and tissues, ferroptosis has been pathogenically associated with brain, kidney, and liver injury/diseases. We discovered that a prokaryotic bacterium, Pseudomonas aeruginosa, that does not contain AA-PE can express lipoxygenase (pLoxA), oxidize host AA-PE to 15-hydroperoxy-AA-PE (15-HOO-AA-PE), and trigger ferroptosis in human bronchial epithelial cells. Induction of ferroptosis by clinical P. aeruginosa isolates from patients with persistent lower respiratory tract infections was dependent on the level and enzymatic activity of pLoxA. Redox phospholipidomics revealed elevated levels of oxidized AA-PE in airway tissues from patients with cystic fibrosis (CF) but not with emphysema or CF without P. aeruginosa. We believe that the evolutionarily conserved mechanism of pLoxA-driven ferroptosis may represent a potential therapeutic target against P. aeruginosa–associated diseases such as CF and persistent lower respiratory tract infections. |
| Databáze: | OpenAIRE |
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