期刊
CELLULAR MICROBIOLOGY
卷 14, 期 5, 页码 698-709出版社
WILEY
DOI: 10.1111/j.1462-5822.2012.01753.x
关键词
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资金
- Cystic Fibrosis Foundation [MACHENG09, ILLEKG08]
- Beverley M. Folger Foundation
- Elizabeth Nash Foundation
- NIH [AI075410, U01HL098964, 2PNE Y018241]
- Cystic Fibrosis Research (New Horizons Grant)
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 mu M) rapidly triggered events commonly associated with the intrinsic apoptotic pathway in JME (CF ?F508CFTR, nasal surface) epithelial cells: depolarization of mitochondrial (mito) membrane potential (??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 Ca2+ and ER-targeted GFP and oxidized contents into the cytosol). Effects began within 5 min and were complete in 12 h. 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 ??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 ??mito and increases in Cacyto like 10-50 mu M 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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