Wei Min, Fu Zhenfa, Wang Che, Zheng Wei, Li Song, Le Weidong
J Biomed Nanotechnol. 2019 Feb 1;15(2):340-351. doi: 10.1166/jbn.2019.2684.
In this study, we aimed to investigate the in vitro impacts and mechanisms of graphene oxide (GO) nanocolloids on autophagy in mouse embryonic stem cells (mESCs). Our results showed that GO nanocolloids treatment induced autophagosome accumulation in mESCs. In addition, we found that this effect was mediated by the blockade of autophagic flux rather than autophagic induction, as evidenced by the elevated autophagic substrate SQSTM1/p62 level and LC3B turn over. Moreover, our data further revealed that GO nanocolloids disrupted autophagic flux by impairing lysosomal function, including lysosomal alkalinization and lysosome membrane permeabilization. These results indicate that GO nanocolloids can block autophagic flux in mESCs via autophagy-lysosome dysfunction. Our findings may reveal the putative mechanism of GO nanocolloids-modulated autophagy and provide experimental evidence for the importance of future safety evaluation of nanomaterials.
在本研究中,我们旨在探究氧化石墨烯(GO)纳米胶体对小鼠胚胎干细胞(mESCs)自噬的体外影响及其机制。我们的结果表明,GO纳米胶体处理可诱导mESCs中自噬体积累。此外,我们发现这种效应是由自噬流的阻断而非自噬诱导介导的,自噬底物SQSTM1/p62水平升高和LC3B周转证明了这一点。此外,我们的数据进一步揭示,GO纳米胶体通过损害溶酶体功能(包括溶酶体碱化和溶酶体膜通透性)来破坏自噬流。这些结果表明,GO纳米胶体可通过自噬-溶酶体功能障碍阻断mESCs中的自噬流。我们的发现可能揭示了GO纳米胶体调节自噬的假定机制,并为未来纳米材料安全性评估的重要性提供实验证据。