Inhibition of apoptosis by P2Y2 receptor activation:: Novel pathways for neuronal survival
Inhibition of apoptosis by P2Y2 receptor activation:: Novel pathways for neuronal survival
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DOI：
10.1523/jneurosci.5338-05.2006
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发表时间：
2006-04-05
影响因子：
5.3
通讯作者：
Insel, PA
中科院分区：
文献类型：
--
作者：
Arthur, DB;Georgi, S;Insel, PA
细胞存活是神经系统发育和维持的重要功能。我们在此证明了通过 P2Y(2) 受体的细胞外核苷酸信号传导在神经元存活中的一个先前未被认识到的作用：PC12（嗜铬细胞瘤 12）细胞和背根神经节神经元受到 ATP、UTP 和 ATP gamma S 的保护，免受血清饥饿诱导的细胞凋亡，这是通过 P2Y2 受体介导的效应，如小干扰 RNA 和遗传敲除模型所证明的那样。这种保护独立于神经元信号传导而发生，但需要 ERK（细胞外信号调节激酶）和 Akt 的 Src 激活。此外，ATP gamma S 和 NGF 协同作用，通过增强 TrkA 信号传导来提高神经元存活率。这些结果定义了抑制细胞凋亡的新机制，暗示平行的相互作用系统——细胞外核苷酸/P2Y(2)受体和神经营养蛋白/TrkA——维持神经元存活。
Cell survival is an essential function in the development and maintenance of the nervous system. We demonstrate here a previously unappreciated role for extracellular nucleotide signaling through the P2Y(2) receptor in the survival of neurons: PC12 (pheochromocytoma 12) cells and dorsal root ganglion neurons are protected from serum starvation-induced apoptosis by ATP, UTP, and ATP gamma S, an effect mediated via P2Y2 receptors, as demonstrated by small interfering RNA and genetic knock-out models. This protection occurs independently of neurophin signaling but requires Src activation of ERK ( extracellular signal-regulated kinase) and Akt. Moreover, ATP gamma S and NGF act synergistically to enhance neuronal survival through enhanced TrkA signaling. The results, which define a novel mechanism for inhibition of apoptosis, implicate parallel, interacting systems-extracellular nucleotides/P2Y(2) receptors and neurotrophin/TrkA - to sustain neuronal survival.