细胞隧道纳米管结构组分对其形成和维持的影响

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

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。

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 methylβcyclodextrin(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.