Pseudomonas aeruginosa biofilm-associated homoserine lactone C12 rapidly activates apoptosis in airway epithelia.
Pseudomonas aeruginosa biofilm-associated homoserine lactone C12 rapidly activates apoptosis in airway epithelia.
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DOI：
10.1111/j.1462-5822.2012.01753.x
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发表时间：
2012-05
影响因子：
3.4
通讯作者：
Machen TE
中科院分区：
文献类型：
--
作者：
Schwarzer C;Fu Z;Patanwala M;Hum L;Lopez-Guzman M;Illek B;Kong W;Lynch SV;Machen TE
铜绿假单胞菌（PA）在囊性纤维化患者的肺中形成生物膜，这是由包括N-（3-氧代十二烷酰基）-L-高丝氨酸内酯C12的群体感应分子调节的过程。C12（10-100 μM）快速触发通常与JME（CFΔ F508 CFTR，鼻表面）上皮细胞内在凋亡途径相关的事件：线粒体（mito）膜电位（Δ mito）的去极化和细胞色素C（cytoC）从线粒体释放到细胞质中以及半胱天冬酶3/7、8和9的激活。C12对内质网也有新的作用（释放Ca 2+和ER靶向的GFP和氧化的内容物进入胞质溶胶）。效果在5分钟内开始，并在1-2小时内完成。C12引起了类似的半胱天冬酶激活和释放细胞色素C从有丝分裂在Calu-3（wtCFTR，支气管腺）细胞，表明C12触发的反应发生类似的不同气道上皮类型。C12对JME和CFTR校正的JME细胞（腺病毒表达）中细胞凋亡反应的三个关键方面（半胱天冬酶3/7、Δ线粒体的去极化和ER中氧化还原电位的降低）具有几乎相同的作用，表明CFTR可能不是C12触发的气道上皮细胞凋亡的重要调节剂。气道培养物暴露于PAO 1 wt的生物膜会导致Δψmito去极化，并导致Cacyto增加，如10-50 μM C12。相比之下，来自PAO 1 ΔlasI（C12缺陷）的生物膜没有影响，表明来自铜绿假单胞菌生物膜的C12可能有助于不能从CF肺中清除的凋亡细胞的积累。提出了一个解释C12效应的模型。
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 (CFΔF508CFTR, nasal surface) epithelial cells: depolarization of mitochondrial (mito) membrane potential (Δψmito) 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 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 Δψmito 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 Δψmito and increases in Cacyto like 10–50 μM C12. In contrast, biofilms from PAO1ΔlasI (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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影响因子：
56.9
作者：
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通讯作者：
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