Mechanisms of P2X7 receptor-mediated ERK1/2 phosphorylation in human astrocytoma cells
Mechanisms of P2X7 receptor-mediated ERK1/2 phosphorylation in human astrocytoma cells
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DOI：
10.1152/ajpcell.00286.2002
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发表时间：
2003-02-01
影响因子：
5.5
通讯作者：
Weisman, GA
中科院分区：
文献类型：
--
作者：
Gendron, FP;Neary, JT;Weisman, GA
星形胶质细胞参与正常和病理性脑功能，在那里它们被激活并经历反应性神经胶质增生。星形胶质细胞已被证明通过激活P2受体（G蛋白偶联的P2 Y受体或P2 X受体，其是配体门控离子通道）来响应细胞外核苷酸。在这项研究中，我们研究了P2 X（7）核苷酸受体（一种在星形胶质细胞中表达的细胞外ATP门控离子通道）的激活可导致ERK 1/2磷酸化的方式。结果显示，P2 X（7）受体激动剂2 '，3'-O-（4-苯甲酰基）苯甲酰基-ATP诱导过表达重组大鼠P2 X（7）受体（rP 2 X（7）-R）的人星形细胞瘤细胞中的ERK 1/2磷酸化，该反应被抑制P2 X（7）受体拮抗剂氧化ATP。其他结果表明，rP 2X（7）-R介导的ERK 1/2磷酸化与富含脯氨酸/Ca 2+激活的酪氨酸激酶Pyk 2、c-Src、磷脂酰肌醇3 '-激酶和蛋白激酶Cdelta活性的磷酸化有关，并且依赖于细胞外Ca 2+的存在。这些结果支持P2 X（7）受体及其信号通路在星形胶质细胞介导的炎症和神经退行性疾病中发挥作用的假设。
Astrocytes are involved in normal and pathological brain functions, where they become activated and undergo reactive gliosis. Astrocytes have been shown to respond to extracellular nucleotides via the activation of P2 receptors, either G protein-coupled P2Y receptors or P2X receptors that are ligand-gated ion channels. In this study, we have examined the manner in which activation of the P2X(7) nucleotide receptor, an extracellular ATP-gated ion channel expressed in astrocytes, can lead to the phosphorylation of ERK1/2. Results showed that the P2X(7) receptor agonist 2', 3'-O-(4-benzoyl) benzoyl-ATP induced ERK1/2 phosphorylation in human astrocytoma cells overexpressing the recombinant rat P2X(7) receptor (rP2X(7)-R), a response that was inhibited by the P2X(7) receptor antagonist, oxidized ATP. Other results suggest that rP2X(7)-R-mediated ERK1/2 phosphorylation was linked to the phosphorylation of the prolinerich/Ca2+-activated tyrosine kinase Pyk2, c-Src, phosphatidylinositol 3'-kinase, and protein kinase Cdelta activities and was dependent on the presence of extracellular Ca2+. These results support the hypothesis that the P2X(7) receptor and its signaling pathways play a role in astrocyte-mediated inflammation and neurodegenerative disease.