Nucleotide release by airway epithelia.
Nucleotide release by airway epithelia.
复制标题
气道上皮释放核苷酸。
DOI：
10.1007/978-94-007-1217-1_1
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发表时间：
2011
影响因子：
--
通讯作者：
Kreda,SilviaM
中科院分区：
文献类型：
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作者：
Lazarowski,EduardoR;Sesma,JulianaI;Seminario,Lucia;EstherJr,CharlesR;Kreda,SilviaM
调节气道先天防御的嘌呤能事件由上皮细胞释放嘌呤启动，其组成性发生并通过化学或机械刺激增强。虽然外部触发器已被详尽审查，本章侧重于目前的知识受体和信号级联介导的核苷酸释放。分泌嘌呤的列表现在包括ATP、ADP、AMP和核苷酸糖，并且涉及至少三种不同的机制，反映了气道上皮的复杂性。首先，组成性机制涉及ATP转运到ER/高尔基体复合体作为蛋白质折叠的能量来源，以及高尔基体衍生的囊泡与质膜的融合。其次，杯状细胞用粘蛋白将ATP包装成颗粒，这些颗粒响应于P2 Y2 R激活和Ca 2+依赖性信号通路而被释放。最后，非粘液细胞支持ATP释放的调节机制，涉及蛋白酶激活受体（PAR）引起的G12/13活化，导致RhoA上的GDP与RhoGEF介导的GTP交换，以及细胞骨架重排。总之，这些途径提供了由嘌呤能信号传导事件调节的上皮反应的微调。
The purinergic events regulating the airways’ innate defenses are initiated by the release of purines from the epithelium, which occurs constitutively and is enhanced by chemical or mechanical stimulation. While the external triggers have been reviewed exhaustively, this chapter focuses on current knowledge of the receptors and signaling cascades mediating nucleotide release. The list of secreted purines now includes ATP, ADP, AMP and nucleotide sugars, and involves at least three distinct mechanisms reflecting the complexity of airway epithelia. First, the constitutive mechanism involves ATP translocation to the ER/Golgi complex as energy source for protein folding, and fusion of Golgi-derived vesicles with the plasma membrane. Second, goblet cells package ATP with mucins into granules, which are discharged in response to P2Y2R activation and Ca2+-dependent signaling pathways. Finally, non-mucous cells support a regulated mechanism of ATP release involving protease activated receptor (PAR)-elicited G12/13activation, leading to the RhoGEF-mediated exchange of GDP for GTP on RhoA, and cytoskeleton rearrangement. Together, these pathways provide fine tuning of epithelial responses regulated by purinergic signaling events.