Overexpression of human CD38/ADP-ribosyl cyclase enhances acetylcholine-induced Ca2+ signalling in rodent NG108-15 neuroblastoma cells
Overexpression of human CD38/ADP-ribosyl cyclase enhances acetylcholine-induced Ca2+ signalling in rodent NG108-15 neuroblastoma cells
复制标题
DOI：
10.1016/j.neures.2006.11.008
复制
发表时间：
2007-03-01
影响因子：
2.9
通讯作者：
Robbins, Jon
中科院分区：
文献类型：
--
作者：
Higashida, Haruhiro;Bowden, Sarah E. H.;Robbins, Jon
在表达M1 mAChRs（NGM 1）的神经母细胞瘤细胞中检测了环ADP核糖（cADPR）及其合成酶CD 38作为毒蕈碱乙酰胆碱受体（mAChRs）下游信号的作用。用野生型和突变型（C119 K/C201 E）人CD 38进一步转化NGM 1细胞。双转化细胞表现出更高的cADPR的形成比ADPR的生产和升高的细胞内游离Ca 2+浓度（[Ca 2 +]i）响应ACh。在代表性的CD 38克隆中详细分析了这些表型。ACh应用引起的细胞内cADPR浓度显著增加，CD 38过表达。通过共聚焦显微镜的数字图像分析显示，控制和过表达的细胞之间的Ca 2+释放的网站的地形分布是不变的。这些结果表明，cADPR是Ca 2+信号传导的细胞内信使，表明CD 38可以促进rnAChR-cADPR信号传导。(c)2006年Elsevier爱尔兰有限公司和日本神经科学学会。All rights reserved.
The role of cyclic ADP-ribose (cADPR) and its synthetic enzyme, CD38, as a downstream signal of muscarinic acetylcholine receptors (mAChRs) was examined in neuroblastoma cells expressing M1 mAChRs (NGM1). NGM1 cells were further transformed with both wild-type and mutant (C119K/C201E) human CD38. The dual transformed cells exhibited higher cADPR formation than ADPR production and elevated intracellular free Ca2+ concentrations ([Ca2+]i) in response to ACh. These phenotypes were analyzed in detail in a representative CD38 clone. The intracellular cADPR concentration by ACh application was significantly increased by CD38 overexpression. Digital image analysis by a confocal microscopy revealed that topographical distribution of the sites of Ca2+ release was unchanged between control and overexpressed cells. These results indicate that cADPR is an intracellular messenger of Ca2+ signalling, suggesting that CD38 can contribute to rnAChR-cADPR signalling. (c) 2006 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.