中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (5): 899-904.doi: 10.4103/1673-5374.290911

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

有助于低渗诱导许旺细胞中ATP释放的细胞大孔径膜通道Pannexin 1 

  

  • 出版日期:2021-05-15 发布日期:2020-12-29
  • 基金资助:

    国家自然科学基金项目（31900718，31872773；国家重点研究发展计划项目（2017YFA0104704）；江苏省教育厅基础研究计划（19KJB180024，18KJB180020）；中国博士后科学基金（2019M651925），江苏省学生创新创业平台培训计划（201810304031Z）；江苏省六个人才高峰项目（WSN-007）

Pannexin 1, a large-pore membrane channel, contributes to hypotonicity-induced ATP release in Schwann cells

Zhong-Ya Wei1, *, #, Hui-Lin Qu1, #, Yu-Juan Dai2, Qian Wang1, Zhuo-Min Ling2, Wen-Feng Su1, Ya-Yu Zhao1, Wei-Xing Shen2, Gang Chen1, 2, 3, *#br#   

  1. 1 Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China;  2 Medical School of Nantong University, Nantong, Jiangsu Province, China;  3 Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
  • Online:2021-05-15 Published:2020-12-29
  • Contact: Zhong-Ya Wei, PhD, weizhongya08yan@126.com; Gang Chen, PhD, MD, chengang6626@ntu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 31900718 (to ZYW), 31872773 (to GC);  the National Key Research and Development Program of China, No. 2017YFA0104704 (to GC); Basic Research Program of the Education Department of Jiangsu Province of China, Nos. 19KJB180024 (to ZYW), 18KJB180020 (to WXS); Postdoctoral Science Foundation of China, No. 2019M651925 (to ZYW), Jiangsu Students’ Platform for Innovation and Entrepreneurship Training Program of China, No. 201810304031Z (to YJD); Six Talent Peaks Project in Jiangsu Province of China, No. WSN-007 (to WXS).

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摘要：

Pannexin作为细胞大孔径的膜通道，对诸多信号分子都具有一定的通透性，尤其是ATP分子。既往研究提示Pannexin 1可在中枢神经系统中的星形胶质细胞、小胶质细胞和神经元中表达，但其在周围神经系统中的分布和功能尚不清楚。此次实验首先观察了Pannexin不同亚型在培养小鼠坐骨神经许旺细胞中的表达，结果显示Pannexin 1在许旺细胞中呈高表达。然后以小干扰RNA或（碳烯醇酮和丙磺舒）阻断Pannexin 1的功能后，可显著降低低渗刺激诱导的ATP释放。此外，通过Rho GTPase抑制剂、Rho-siRNA以及微管破坏剂nocodazole或细胞松弛素D干预许旺细胞，证实低渗诱导的ATP释放的过程依赖于细胞内的RhoA及骨架蛋白。结果表明Pannexin 1可通过调节RhoA和细胞骨架排列参与许旺细胞中ATP的释放。实验于2018年8月5日经南通大学动物伦理委员会批准，批准号S20180806-002。

https://orcid.org/0000-0003-3669-5687 (Gang Chen)

关键词: 周围神经, 神经元, 损伤, Pannexin 1, ATP, 许旺细胞, Ras同源家族成员A, 细胞骨架

Abstract: Pannexin 1 (Panx 1), as a large-pore membrane channel, is highly permeable to ATP and other signaling molecules. Previous studies have demonstrated the expression of Panx 1 in the nervous system, including astrocytes, microglia, and neurons. However, the distribution and function of Panx 1 in the peripheral nervous system are not clear. Blocking the function of Panx 1 pharmacologically (carbenoxolone and probenecid) or with small interfering RNA targeting pannexins can greatly reduce hypotonicity-induced ATP release. Treatment of Schwann cells with a Ras homolog family member (Rho) GTPase inhibitor and small interfering RNA targeting Rho or cytoskeleton disrupting agents, such as nocodazole or cytochalasin D, revealed that hypotonicity-induced ATP release depended on intracellular RhoA and the cytoskeleton. These findings suggest that Panx 1 participates in ATP release in Schwann cells by regulating RhoA and the cytoskeleton arrangement. This study was approved by the Animal Ethics Committee of Nantong University, China (No. S20180806-002) on August 5, 2018.

Key words: ATP, cytoskeleton, injury, neuron, pannexin 1, peripheral nerve, Ras homolog family member A, Schwann cells