| Pseudomonas aeruginosa biofilm-associated homoserine lactone C12 rapidly activates apoptosis in airway epithelia. | |
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MedLine Citation:
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PMID: 22233488 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Pseudomonas aeruginosa (PA) forms biofilms in lungs of cystic fibrosis CF) patients, a process regulated by quorum sensing molecules including N-(3-oxododecanoyl)-L-homoserine lactone, C12. C12 (10-100 µM) rapidly triggered events commonly associated with the intrinsic apoptotic pathway in JME (CF ?F508CFTR, nasal surface) epithelial cells: depolarization of mitochondrial (mito) membrane potential (?ψ(mito) ) and release of cytochrome C (cytoC) from mitos into cytosol and activation of caspases 3/7, 8 and 9. C12 also had novel effects on the endoplasmic reticulum (release of both Ca(2+) and ER-targeted GFP and oxidized contents into the cytosol). Effects began within 5 minutes and were complete in 1-2 hrs. C12 caused similar activation of caspases and release of cytoC from mitos in Calu-3 (wtCFTR, bronchial gland) cells, showing that C12-triggered responses occurred similarly in different airway epithelial types. C12 had nearly identical effects on three key aspects of the apoptosis response (caspase 3/7, depolarization of ?ψ(mito) and reduction of redox potential in the ER) in JME and CFTR-corrected JME cells (adenoviral expression), showing that CFTR was likely not an important regulator of C12-triggered apoptosis in airway epithelia. Exposure of airway cultures to biofilms from PAO1wt caused depolarization of ?ψ(mito) and increases in Ca(cyto) like 10-50 µM C12. In contrast, biofilms from PAO1?lasI (C12 deficient) had no effect, suggesting that C12 from P. aeruginosa biofilms may contribute to accumulation of apoptotic cells that cannot be cleared from CF lungs. A model to explain the effects of C12 is proposed. |
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Authors:
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Christian Schwarzer; Zhu Fu; Maria Patanwala; Lauren Hum; Mirielle Lopez-Guzman; Beate Illek; Weidong Kong; Susan V Lynch; Terry E Machen |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-10 |
Journal Detail:
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Title: Cellular microbiology Volume: - ISSN: 1462-5822 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100883691 Medline TA: Cell Microbiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 Blackwell Publishing Ltd. |
Affiliation:
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Department of Molecular and Cell Biology University of California Berkeley, CA 94720-3200 Children's Hospital Oakland Research Institute 5700 Martin Luther King Jr Way Oakland, California 94609 Division of Gastroenterology 513 Parnassus Avenue, Room S-357 University of California San Francisco, CA 94143-0358. |
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