衣霉素通过诱导内质网应激抑制乙型肝炎e抗原分泌

目的研究N-糖基化抑制剂衣霉素抑制乙型肝炎e抗原(HBeAg)分泌的机制,为今后探索直接抑制HBeAg分泌的高效抗HBV方法提供基础。方法观察衣霉素在HepG2.2.15细胞模型上对HBeAg分泌和内质网应激的影响;采用Western印迹比较研究衣霉素对胞质和包含内质网的非胞质中的HBeAg前体的影响。结果在HepG2.2.15细胞上,衣霉素显著减少HBeAg在培养上清中的含量,并诱导代表内质网应激的拼接xbp-1 mRNA形成。衣霉素在不显著影响胞质中HBeAg前体和β-肌动蛋白的情况下显著减少非胞质中这些蛋白的水平。结论衣霉素抑制HBeAg分泌不是糖基化抑制的直接结果,而是诱导内质网应激的效应。

Tunicamycin inhibit the secretion of hepatitis B e antigen by induction of endoplasmic reticulum stress

Objective To study on the mechanism for N-glycosylation inhibitor tunicamycin to inhibit the secretion of hepatitis B e antigen（HBeAg）, and provide helpful information to develop HBeAg secretion-targeting strategy for antiHBV in the future. Methods The influences of tunicamycin on HBeAg secretion and endoplasmic reticulum stress in HepG2.2.15 cells were investigated.The influences of tunicamycin on the distribution of HBeAg precursor in cytosol and non-cytosol including endoplasmic reticulum were comparatively studied using Western-blot analysis. Results HBeAg level in culture media was significantly induced by tunicamycin,which could induce the formation of endoplasmic reticulum stress-representing spliced mRNA of xbp-1 in HepG2.2.15 cells.Furthermore,the levels of HBeAg precursor andβ-actin in non-cytosol decreased dramatically under the effect of tunicamycin without interference with their levels in cytosol. Conclusion Tunicamycin can inhibit the HBeAg secretion by inducting endoplasmic reticulum stress rather than inhibition of N-glycosylation.