Nicotinic acid adenine dinucleotide phosphate (NAADP(+)) is an essential regulator of T-lymphocyte Ca(2+)-signaling.

Nicotinic acid adenine dinucleotide phosphate (NAADP(+)) is an essential regulator of T-lymphocyte Ca(2+)-signaling.
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DOI:
10.1083/jcb.150.3.581
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发表时间:
2000-08-07
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Guse AH
Guse AH
中科院分区:
其他
文献类型:
--
作者:
Berg I;Potter BV;Mayr GW;Guse AH

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微量注射人Jurkat t淋巴细胞与烟酸腺嘌呤二核苷酸磷酸(NAADP+)剂量依赖性刺激细胞内Ca2+信号。在浓度为10 nM时,NAADP+引起重复和持久的低振幅Ca2+振荡,而在50和100 nM时,观察到快速和高的初始Ca2+峰值,随后观察到一系列较小的Ca2+振荡。较高浓度的NAADP+ (1 μM和10 μM)逐渐降低了Ca2+的初始峰,在100 μM处Ca2+信号完全自失活。NAADP+的作用是特异性的,因为它在烟酰胺腺嘌呤二核苷酸磷酸中没有观察到。肌醇1,4,5-三磷酸和环腺苷二磷酸介导的Ca2+信号通过共同注射自失活浓度的NAADP+有效地抑制。最重要的是,微量注射自失活浓度的NAADP+完全消除了随后通过T细胞受体/CD3复合物对Ca2+信号的刺激,表明功能良好的NAADP+ Ca2+释放系统对T淋巴细胞Ca2+信号传导至关重要。
Microinjection of human Jurkat T-lymphocytes with nicotinic acid adenine dinucleotide phosphate (NAADP+) dose-dependently stimulated intracellular Ca2+-signaling. At a concentration of 10 nM NAADP+ evoked repetitive and long-lasting Ca2+-oscillations of low amplitude, whereas at 50 and 100 nM, a rapid and high initial Ca2+-peak followed by trains of smaller Ca2+-oscillations was observed. Higher concentrations of NAADP+ (1 and 10 μM) gradually reduced the initial Ca2+-peak, and a complete self-inactivation of Ca2+-signals was seen at 100 μM. The effect of NAADP+ was specific as it was not observed with nicotinamide adenine dinucleotide phosphate. Both inositol 1,4,5-trisphosphate– and cyclic adenosine diphosphoribose–mediated Ca2+-signaling were efficiently inhibited by coinjection of a self-inactivating concentration of NAADP+. Most importantly, microinjection of a self-inactivating concentration of NAADP+ completely abolished subsequent stimulation of Ca2+-signaling via the T cell receptor/CD3 complex, indicating that a functional NAADP+ Ca2+-release system is essential for T-lymphocyte Ca2+-signaling.
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