Pseudomonas aeruginosa utilizes host polyunsaturated phosphatidylethanolamines to trigger theft-ferroptosis in bronchial epithelium.

Autor: Dar HH; Department of Environmental and Occupational Health and Center for Free Radical and Antioxidant Health and., Tyurina YY; Department of Environmental and Occupational Health and Center for Free Radical and Antioxidant Health and., Mikulska-Ruminska K; Department of Computational and System Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.; Institute of Physics, Nicolaus Copernicus University, Torun, Poland., Shrivastava I; Department of Environmental and Occupational Health and Center for Free Radical and Antioxidant Health and.; Department of Computational and System Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Ting HC; Department of Environmental and Occupational Health and Center for Free Radical and Antioxidant Health and., Tyurin VA; Department of Environmental and Occupational Health and Center for Free Radical and Antioxidant Health and., Krieger J; Department of Computational and System Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., St Croix CM; Department of Cell Biology., Watkins S; Department of Cell Biology., Bayir E; Department of Environmental and Occupational Health and Center for Free Radical and Antioxidant Health and., Mao G; Department of Environmental and Occupational Health and Center for Free Radical and Antioxidant Health and.; Department of Critical Care Medicine., Armbruster CR; Department of Microbiology and Molecular Genetics, and., Kapralov A; Department of Environmental and Occupational Health and Center for Free Radical and Antioxidant Health and., Wang H; Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Parsek MR; Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington, USA., Anthonymuthu TS; Department of Environmental and Occupational Health and Center for Free Radical and Antioxidant Health and.; Department of Critical Care Medicine., Ogunsola AF; Department of Microbiology and Molecular Genetics, and., Flitter BA; Department of Microbiology and Molecular Genetics, and., Freedman CJ; Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, California, USA., Gaston JR; Department of Microbiology and Molecular Genetics, and., Holman TR; Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, California, USA., Pilewski JM; Department of Medicine and., Greenberger JS; Department of Radiation Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Mallampalli RK; Department of Medicine and.; Medical Specialty Service Line, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA., Doi Y; Department of Medicine and., Lee JS; Department of Medicine and., Bahar I; Department of Computational and System Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Bomberger JM; Department of Microbiology and Molecular Genetics, and., Bayır H; Department of Environmental and Occupational Health and Center for Free Radical and Antioxidant Health and.; Department of Critical Care Medicine., Kagan VE; Department of Environmental and Occupational Health and Center for Free Radical and Antioxidant Health and.; Department of Radiation Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.; Department of Chemistry and.; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.; Laboratory of Navigational Redox Lipidomics, Institute of Regenerative Medicine, IM Sechenov Moscow State Medical University, Moscow, Russia.
Jazyk: angličtina
Zdroj: The Journal of clinical investigation [J Clin Invest] 2018 Oct 01; Vol. 128 (10), pp. 4639-4653. Date of Electronic Publication: 2018 Sep 10.
DOI: 10.1172/JCI99490
Abstrakt: 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: MEDLINE