Interaction between ATP and nerve growth factor signalling in the survival and neuritic outgrowth from PC12 cells
Interaction between ATP and nerve growth factor signalling in the survival and neuritic outgrowth from PC12 cells
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DOI：
10.1016/s0306-4522(01)00431-6
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发表时间：
2001-01-01
期刊：
影响因子：
3.3
通讯作者：
Volonté, C
中科院分区：
文献类型：
--
作者：
D'Ambrosi, N;Murra, B;Volonté, C
在先前的研究中，我们使用P2受体拮抗剂来抑制神经生长因子（NGF）在PC 12细胞中促进和协调的各种反应，我们认为P2受体参与了NGF信号级联反应。在本文中，我们研究了细胞外P2受体激动剂作为神经营养因子的直接作用。在用NGF引发PC 12细胞后，ATP和2-Cl-ATP促进神经突再生，并且效果是剂量依赖性的，EC 50分别为约5和3 μ M。携带神经突的细胞团的数量在第1天被最大程度地诱导，并且通过ATP维持长达约1周，或通过2-Cl-ATP维持长达至少2周。P1受体或细胞内肌苷参与这些行动被排除在外，而各种拮抗剂的P2受体的抑制。此外，在神经突再生条件下，NGF和ATP引起P2 X（2）、P2 X（3）、P2 X（4）和P2 Y（2）受体蛋白的直接上调，但不引起P2 Y（4）受体蛋白的上调，以及细胞外信号调节激酶（Erk）1-2酪氨酸/苏氨酸磷酸化和激活。最后，ATP，2-Cl-ATP和ATP γ S增强了次优浓度的NGF诱发的神经突起始，ATP和2-Cl-ATP完全维持了血清剥夺后的PC 12细胞的存活，我们的结果证实了P2受体激动剂可以作为神经细胞的神经营养因子，并表明ATP和NGF在其靶细胞上触发的信号通路中可能存在相互作用。(C)2001年IBRO。由爱思唯尔科技有限公司出版。保留所有权利。
In a previous study we used P2 receptor antagonists to inhibit diverse responses that nerve growth factor (NGF) promotes and coordinates in PC12 cells and we suggested that P2 receptors partake in the NGF signalling cascade. In this paper, we examine the direct role of extracellular P2 receptor agonists as neurotrophic factors. ATP and 2-Cl-ATP promote neurite regeneration after priming PC12 cells with NGF and the effect is dose-dependent, with an EC50 of about 5 and 3 muM, respectively. The number of cell clumps bearing neurites was maximally induced in day 1 and it was maintained up to about one week by ATP, or up to at least 2 weeks by 2-Cl-ATP. The involvement of P1 receptors or intracellular inosine in these actions was excluded, whereas various antagonists of P2 receptors were inhibitory. Moreover, NGF and ATP caused a direct up-regulation of P2X(2), P2X(3), P2X(4) and P2Y(2), but not P2Y(4) receptor proteins under neurite-regenerating conditions, as well as extracellular signal-regulated kinase (Erk)1-2 tyrosine/threonine phosphorylation and activation. Finally, ATP, 2-Cl-ATP and ATP gammaS enhanced neurite initiation evoked by sub-optimal NGF concentrations and ATP and 2-Cl-ATP fully sustained survival of PC12 cells after serum deprivation.Our results establish that P2 receptor agonists can behave as neurotrophic factors for neuronal cells and suggest a potential interplay between ATP and NGF in the signalling pathways triggered on their target cells. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.