Cell-permeant NAADP:: A novel chemical tool enabling the study of Ca2+ signalling in intact cells

Cell-permeant NAADP:: A novel chemical tool enabling the study of Ca2+ signalling in intact cells
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DOI:
10.1016/j.ceca.2007.08.006
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发表时间:
2008-06-01
期刊:
影响因子:
4
通讯作者:
Churchill, Grant C.
Churchill, Grant C.
中科院分区:
生物学2区
文献类型:
--
作者:
Parkesh, Raman;Lewis, Alexander M.;Churchill, Grant C.

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NAADP(nicotinic acid adenine dinucleotide phosphate)是最近发现的第二信使,因此,我们还需要了解它在健康和疾病中的功能。这一基础研究的瓶颈是由于NAADP,像所有的第二信使一样,被充电以防止它泄漏出细胞。这使得有效的生物学,但在实验中带来了困难,因为它必须被注射,通过脂质体加载或电穿孔,这些技术要求很高,并且只能在某些单细胞制剂中使用。对于更好地理解的第二信使肌醇1,4,5-三磷酸,已经获得了巨大的成功与细胞渗透衍生物,其中带电基团通过酯化掩蔽。我们现在报告NAADP-AM作为NAADP的细胞渗透性类似物,其被吸收到细胞中并诱导NAADP介导的Ca 2+信号传导。NAADP-AM是一种强大的化学工具,将在广泛的系统中具有巨大的生物效用,并将极大地促进对NAADP在健康和疾病中的作用的研究。(C)2007年爱思唯尔有限公司保留所有战斗。
NAADP (nicotinic acid adenine dinucleotide phosphate) is a recently discovered second messenger, and as Such, we have much yet to learn about its functions in health and disease. A bottleneck in this basic research is due to NAADP, like all second messengers, being charged to prevent it from leaking out of cells. This makes for effective biology, but imposes difficulties in experiments, as it must be injected, loaded via liposomes, or electroporated, techniques that are highly technically demanding and are possible only in certain single cell preparations. For the better understood second messenger inositol 1,4,5-trisphosphate, great success has been obtained with cell-permeant derivatives where the charged groups are masked through esterification. We now report NAADP-AM as a cell-permeant analogue of NAADP that is taken up into cells and induces NAADP-mediated Ca2+ signalling. NAADP-AM is a powerful chemical tool that will be of enormous biological utility in a wide range of systems and will greatly facilitate research into the role of NAADP in health and disease. (C) 2007 Elsevier Ltd. All fights reserved.