Involvement of purinergic 2X(4) receptor in glycoprotein 120-induced pyroptosis in dorsal root ganglia
Involvement of purinergic 2X(4) receptor in glycoprotein 120-induced pyroptosis in dorsal root ganglia
复制标题
嘌呤能 2X(4) 受体参与糖蛋白 120 诱导的背根神经节细胞焦亡
DOI：
10.1111/jnc.14850
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发表时间：
2019
影响因子：
4.7
通讯作者：
Liang Shangdong
中科院分区：
文献类型：
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作者：
Zhao Shanhong;Zhou Yanhong;Fan Yang;Gong Yingxin;Yang Jingjian;Yang Runan;Li Lin;Zou Lifang;Xu Xiumei;Li Guilin;Liu Shuangmei;Zhang Chunping;Li Guodong;Liang Shangdong
细胞焦亡是一种程序性细胞死亡，表现出 caspase-1 依赖性和促炎症特征。高三磷酸腺苷释放导致的嘌呤能 2X4(P2X4) 受体激活可诱发炎症。 1型人类免疫缺陷病毒的包膜糖蛋白120（gp120）被认为是导致神经元损伤的主要病原体之一。在这项研究中，我们研究了 P2X4 受体激活在大鼠背根神经节 (DRG) 培养的卫星胶质细胞 (SGC) 中 gp120 触发的细胞焦亡中的可能作用。使用MTS测定、TdT介导的dUTP缺口末端标记测定、实时RT-PCR和蛋白质印迹等方法。结果表明，gp120培养24 h后，DRG SGCs中P2X4受体的表达上调。 gp120 处理导致的 SGC 活力下降幅度最大，伴随着阳性焦亡细胞和细胞乳酸脱氢酶释放的显着增加，白介素-1β、白介素-18、活性 caspase-1 和 NOD 样受体家族、含有 1 的热蛋白结构域和 p38MAPK 磷酸化增强的水平升高。当用靶向 P2X4 受体的短发夹 RNA 处理 DRG 的 SGC 时，这些由 gp120 引起的异常变化被显着抑制，细胞活力显着提高。我们的数据表明，沉默 P2X4 受体可以有效对抗 gp120 诱导的焦亡，该焦亡是由 NOD 样受体家族、包含 1 个炎性体的 Pyrin 结构域和 DRG SGC 中的 caspase-1 信号传导介导的。
Pyroptosis is a type of programmed cell death, displaying caspase‐1‐dependent and pro‐inflammatory features. Purinergic 2X4(P2X4) receptor activation in response to high‐adenosine triphosphate release can induce inflammation. Envelope glycoprotein 120 (gp120) of human immunodeficiency virus type 1 is considered one of the primary pathogens leading to neuronal injury. In this study, we investigated the possible role of P2X4receptor activation in gp120‐triggered pyroptosis in cultured satellite glial cells (SGCs) of rat dorsal root ganglia (DRG). MTS assay, TdT‐mediated dUTP Nick‐end labeling assay, real‐time RT‐PCR, and western blottinget al.methods were used. The results indicated that the expression of P2X4receptor in SGCs of DRG was up‐regulated upon cultured with gp120 for 24 h. The highest decrease in viability of SGCs due to gp120 treatment was accompanied by marked increases of positive pyroptosis cells and cellular lactate dehydrogenase release, elevated levels of interleukin‐1β, interleukin‐18, active caspase‐1 and NOD‐like receptor family, pyrin domain containing 1, and enhanced phosphorylation of p38MAPK. These abnormal changes because of gp120 were significantly inhibited and cell viability was markedly improved when SGCs of DRG were treated with short hairpin RNAs targeting P2X4receptor. Our data suggest that silencing of P2X4receptor may act effectively against gp120‐induced pyroptosis mediated by the activation of NOD‐like receptor family, pyrin domain containing 1 inflammasome and caspase‐1 signaling in SGCs of DRG.