Denatonium inhibits growth and induces apoptosis of airway epithelial cells through mitochondrial signaling pathways.
Denatonium inhibits growth and induces apoptosis of airway epithelial cells through mitochondrial signaling pathways.
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地那铵通过线粒体信号通路抑制气道上皮细胞生长并诱导其凋亡
DOI：
10.1186/s12931-015-0183-9
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发表时间：
2015-02-05
影响因子：
5.8
通讯作者：
Bai C
中科院分区：
文献类型：
--
作者：
Wen X;Zhou J;Zhang D;Li J;Wang Q;Feng N;Zhu H;Song Y;Li H;Bai C
地那铵是一种广泛应用的苦味受体激动剂，它能激活多种细胞上的苦味受体，通过细胞内Ca ~（2+）依赖性途径在化学物质释放、纤毛搏动和平滑肌舒张等方面发挥重要作用。然而，地那铵对气道上皮细胞增殖和细胞成分（如线粒体）完整性的影响尚未研究。在这项研究中，我们假设地那铵可能通过损伤线粒体而引起气道上皮细胞的损伤。方法采用电子显微镜、细胞计数试剂盒-8（CCK-8）法和流式细胞术分别检测细胞形态、增殖和细胞周期。透射电子显微镜（TEM）用于检查线粒体的完整性。JC-1染料和蛋白质印迹技术被用来测量线粒体膜电位和蛋白质expressions.ResultsFor气道上皮细胞，我们观察到，denatonium显着影响细胞形态，减少细胞增殖，并以剂量依赖性的方式减少S期细胞的数量。TEM分析表明，denatonium导致大幅度肿胀的线粒体，这是证实了线粒体膜电位的损失，下调Bcl-2蛋白和随后的增强线粒体释放细胞色素c和Smac/DIABLO后denatonium treatment.ConclusionsIn这项研究中，我们首次证明，denatonium损伤线粒体，从而诱导气道上皮细胞凋亡。
BackgroundDenatonium, a widely used bitter agonist, activates bitter taste receptors on many cell types and plays important roles in chemical release, ciliary beating and smooth muscle relaxation through intracellular Ca2+-dependent pathways. However, the effects of denatonium on the proliferation of airway epithelial cells and on the integrity of cellular components such as mitochondria have not been studied. In this study, we hypothesize that denatonium might induce airway epithelial cell injury by damaging mitochondria.MethodsBright-field microscopy, cell counting kit-8 (CCK-8) assay and flow cytometry analysis were used to examine cellular morphology, proliferation and cell cycle, respectively. Transmission electron microscopy (TEM) was used to examine mitochondrial integrity. JC-1 dye and western blotting techniques were used to measure mitochondrial membrane potential and protein expression, respectively.ResultsFor airway epithelial cells, we observed that denatonium significantly effects cellular morphology, decreases cell proliferation and reduces the number of cells in S phase in a dose-dependent manner. TEM analysis demonstrated that denatonium causes large amplitude swelling of mitochondria, which was confirmed by the loss of mitochondrial membrane potential, the down-regulation of Bcl-2 protein and the subsequent enhancement of the mitochondrial release of cytochrome c and Smac/DIABLO after denatonium treatment.ConclusionsIn this study, we demonstrated for the first time that denatonium damages mitochondria and thus induces apoptosis in airway epithelial cells.
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气道平滑肌上的苦味受体通过局部钙信号传导和反向阻塞来支气管扩张。
影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1073/pnas.1402436111
发表时间：
2014-06-03
影响因子：
11.1
作者：
Deckmann, Klaus;Filipski, Katharina;Kummer, Wolfgang
通讯作者：
Kummer, Wolfgang
影响因子：
4.1
作者：
Huang, Bin;Meng, Ning;Miao, JunYing
通讯作者：
Miao, JunYing
影响因子：
1.6
作者：
Sawano, S;Seto, E;Hayashi, Y
通讯作者：
Hayashi, Y
影响因子：
2.9
作者：
SPIELMAN, AI;HUQUE, T;BRAND, JG
通讯作者：
BRAND, JG