Porphyromonas gingivalis-nucleoside-diphosphate-kinase inhibits ATP-induced reactive-oxygen-species via P2X7 receptor/NADPH-oxidase signalling and contributes to persistence.
Porphyromonas gingivalis-nucleoside-diphosphate-kinase inhibits ATP-induced reactive-oxygen-species via P2X7 receptor/NADPH-oxidase signalling and contributes to persistence.
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DOI：
10.1111/cmi.12089
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发表时间：
2013-06
影响因子：
3.4
通讯作者：
Yilmaz Ö
中科院分区：
文献类型：
--
作者：
Choi CH;Spooner R;DeGuzman J;Koutouzis T;Ojcius DM;Yilmaz Ö
P2 X7受体与“危险信号”，细胞外ATP（eATP）的连接，最近已被证明会导致巨噬细胞内活性氧（ROS）的产生。我们发现，原代牙龈上皮细胞（GECs）产生持续的，强大的细胞活性氧刺激后，eATP。通过药理学抑制和RNA干扰测定，ROS的诱导由P2 X7受体信号传导介导，并与NADPH氧化酶活化偶联。此外，牙龈卟啉单胞菌，一种口腔条件致病菌，上调抗氧化谷胱甘肽反应，调节eATP诱导的细胞溶质和线粒体ROS产生通过P2 X7/NADPH-氧化酶相互作用组，并随后通过牙龈卟啉单胞菌效应物，核苷二磷酸激酶（Ndk）的时间分泌阻断GECs中的氧化应激。ndk缺陷型牙龈卟啉单胞菌突变体缺乏抑制ROS产生的能力，并且在eATP刺激后在细胞内持续存在。用重组Ndk处理显著减少eATP诱发的ROS产生。牙龈卟啉单胞菌感染引起抗氧化线粒体UCP 2水平的强烈的、时间依赖性的增加，而ndk缺陷突变体没有引起任何变化。结果揭示了一种新的信号级联反应，它与eATP信号和ROS调节紧密耦合。牙龈卟啉单胞菌的Ndk通过分泌Ndk来抵消这些抗微生物信号传导活性，从而有助于病原体的成功持续。
Ligation of P2X7 receptors with a “danger signal”, extracellular ATP (eATP), has recently been shown to result in production of intracellular reactive-oxygen-species (ROS) in macrophages. We show that primary gingival epithelial cells (GECs) produce sustained, robust cellular ROS upon stimulation by eATP. The induction of ROS was mediated by P2X7 receptor signaling coupled with NADPH-oxidase activation, as determined by pharmacological inhibition and RNA-interference. Furthermore, Porphyromonas gingivalis, an oral opportunistic pathogen, up-regulated the antioxidant glutathione response, modulated eATP-induced cytosolic and mitochondrial ROS generated the through P2X7/NADPH-oxidase interactome, and subsequently blocked oxidative-stress in GECs via temporal secretion of a P. gingivalis effector, nucleoside-diphosphate-kinase (Ndk). An ndk-deficient P. gingivalis mutant lacked the ability to inhibit ROS production and persist intracellularly following eATP stimulation. Treatment with recombinant Ndk significantly diminished eATP-evoked ROS production. P. gingivalis infection elicited a strong, time-dependent increase in anti-oxidative mitochondrial UCP2 levels, whereas ndk-deficient mutant did not cause any change. The results reveal a novel signaling cascade that is tightly coupled with eATP signaling and ROS regulation. Ndk by P. gingivalis counteracts these antimicrobial signaling activities by secreting Ndk, thus contributing to successful persistence of the pathogen.
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影响因子：
3.1
作者：
Bryan, Nicholas;Ahswin, Helen;Hunt, John A.
通讯作者：
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DOI：
10.1016/j.biocel.2010.04.015
发表时间：
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影响因子：
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作者：
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作者：
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