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Title:: Effect of the components of tunneling nanotube on its formation and stability

Author(s):: LI Aoqi; DENG Linhong; WANG Xiang; Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou 213164, China

Keywords:: Tunneling nanotube; Cell-cell communication; F-actin; Cadherin; Cholesterol; HEK293 cells

摘要:: 由于细胞隧道纳米管(tunneling nanotube，TNT)生成的分子机制的多样性，目前尚未发现靶向TNT的低毒、广谱药物。本研究使用细胞松弛素D (cytochalasin D, cytoD)、乙二醇双(2-氨基乙基醚)四乙酸(EGTA)、甲基β环糊精（Mbc）分别破坏HEK293细胞间TNT结构的微丝、N型钙黏蛋白和胆固醇，来研究TNT结构组分对其形成和维持的影响。结果表明，破坏F-actin对TNT的生成频率的抑制作用最为明显，而对已存在的TNT的生存时间影响较小，钙黏蛋白是影响TNT的生存时间的关键分子，而胆固醇的水平对TNT的生成频率和生存时间的作用均有一定影响。本研究表明，通过干预TNT的结构组分控制TNT数量，有望成为筛选靶向 TNT 的药物的新方向。

Abstract:: Due to the diversity of the molecular mechanisms of formation, low-toxic, broad-spectrum drugs targeting tunneling nanotube（TNT）have not yet been developed. In order to study the influence of TNT structural components on its formation and maintenance, cytochalasin D (cytoD), ethylene glycol bis(2-aminoethyl ether) tetraacetic acid (EGTA), and methyl β cyclodextrin (Mbc) were used to destroy the microfilament，cadherin and cholesterol of the TNT structurein HEK293 cells. The results showed that destroyed F-actin had the most obvious inhibitory effect on the formation frequency of TNT, but had little effect on the lifetime of existing TNT. N-cadherin was a key molecule that affected the lifetime of TNT. The level of cholesterol had a certain effect on the formation frequency and life time of TNT. These results indicate that the control of TNT levels by interfering with its structural components is expected to provide a new direction for screening drugs targeting TNT.