2,5-Hexanedione induces autophagic death of VSC4.1 cells via a PI3K/Akt/mTOR pathway,Molecular BioSystems

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2,5-Hexanedione induces autophagic death of VSC4.1 cells via a PI3K/Akt/mTOR pathway
Molecular BioSystems Pub Date : 2017-07-28 00:00:00 , DOI: 10.1039/c7mb00001d
Huai Guan _{1,

2} , Hua Piao _{2,

3,

4,

5} , Zhiqiang Qian _{2,

4,

5,

6} , Xueying Zhou _{2,

4,

5,

6} , Yijie Sun _{2,

4,

5,

6} , Chenxue Gao _{2,

4,

5,

6} , Shuangyue Li _{2,

4,

5,

6} , Fengyuan Piao _{2,

4,

5,

6}

Affiliation

2,5-Hexanedione (HD) is an important bioactive metabolite of n-hexane, which mediates the neurotoxicity of the parent compound. Increasing evidence suggests that over-activated autophagy can lead to autophagic neuronal death; however, whether the excessive autophagy is involved in HD-induced neurotoxicity remains unknown. To investigate the effect of HD on autophagy and to find its underlying mechanism, we respectively treated VSC4.1 cells with 5, 15 and 25 mM HD for 24 h. Our results show that HD induced excessive autophagy of VSC4.1 cells in a dose-dependent manner, also, the over-activated autophagy was significantly mitigated in the presence of PI3K activator or Akt activator or mTOR activator. These results indicate that HD induces excessive autophagy of VSC4.1 cells by repressing the PI3K/Akt/mTOR signaling pathway. LDH assay showed that HD contributed to a concentration dependent increase in VSC4.1 cell death, which was significantly reduced by the administration of PIK-III, an autophagy inhibitor. These results also indicate that HD induces autophagic death of VSC4.1 cells via the signaling pathway.

中文翻译：

2,5-己二酮通过PI3K / Akt / mTOR途径诱导VSC4.1细胞自噬死亡

2,5-己二酮（HD）是n的重要生物活性代谢产物-己烷，介导母体化合物的神经毒性。越来越多的证据表明，过度自噬会导致自噬神经元死亡。然而，过度自噬是否参与了HD诱导的神经毒性尚不清楚。为了研究HD对自噬的影响并发现其潜在机制，我们分别用5、15和25 mM HD处理了VSC4.1细胞24小时。我们的结果表明，HD以剂量依赖的方式诱导VSC4.1细胞过度自噬，而且，在存在PI3K激活剂或Akt激活剂或mTOR激活剂的情况下，过度激活的自噬作用得到了显着缓解。这些结果表明HD通过抑制PI3K / Akt / mTOR信号传导途径诱导VSC4.1细胞过度自噬。LDH测定显示HD导致VSC4浓度依赖性增加。1细胞死亡，通过自噬抑制剂PIK-III的使用可显着降低死亡。这些结果还表明HD诱导VSC4.1细胞自噬死亡通过信号通路。

更新日期：2017-07-30

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