tert-Butyl-p-benzoquinone induces autophagy by inhibiting the Akt/mTOR signaling pathway in RAW 264.7 cells
tert-Butyl-p-benzoquinone induces autophagy by inhibiting the Akt/mTOR signaling pathway in RAW 264.7 cells
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叔丁基对苯醌通过抑制 RAW 264.7 细胞中的 Akt/mTOR 信号通路诱导自噬
DOI：
10.1039/d0fo00281j
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发表时间：
2020-05-01
期刊：
影响因子：
6.1
通讯作者：
Nie, Xiaohua
中科院分区：
文献类型：
--
作者：
Meng, Xianghe;Xia, Chaosheng;Nie, Xiaohua
叔丁基对苯醌（TBBQ）是食品中叔丁基对苯二酚的代谢产物，具有细胞毒性，其潜在机制尚不清楚。本研究采用MTT法测定了浓度为0.5-10 μg mL(-1)的TBBQ后RAW 264.7细胞的活力。结果表明，TBBQ 以剂量依赖性方式降低活力。单丹磺酰尸胺 (MDC) 染色结果表明 TBBQ 诱导发生自噬，表现为 LC3-II 激活，同时 Beclin1 水平升高和 p62 水平降低。 TBBQ 暴露导致的脂质过氧化物升高和 SOD 活性降低表明 ROS 过量产生，这可能是基因毒性应激蛋白 p53 增加的原因。 p53 的上调和 Akt 水平的降低都会抑制 mTOR，从而激活自噬。添加 3-MA 抵消了 TBBQ 对 ATG 蛋白和细胞活力的影响。所有这些结果表明，TBBQ 主要通过抑制 Akt/mTOR 信号通路来诱导 RAW 264.7 细胞自噬，并且表明 ROS 参与了这种调节。
tert-Butyl-p-benzoquinone (TBBQ), a metabolite of tert-butylhydroquinone from food, has cytotoxicity, the underlying mechanism of which is not clear. In this study, the viability of RAW 264.7 cells exposed to TBBQ at concentrations of 0.5-10 mu g mL(-1) was assayed by MTT. Results suggest that TBBQ decreased the viability in a dose-dependent manner. Monodansylcadaverine (MDC) staining results indicate the occurrence of autophagy induced by TBBQ, which was manifested by activation of LC3-II concurrent with the increased levels of Beclin1 and reduced levels of p62. Elevated lipid peroxide and decreased SOD activity by TBBQ exposure suggest the overproduction of ROS, which may account for the increase in the genotoxic stress protein p53. Both upregulation of p53 and reduction of Akt levels inhibited mTOR, which activated autophagy. Addition of 3-MA counteracted the impact of TBBQ on ATG proteins and cell viability. All of these results suggest that TBBQ induces autophagy of RAW 264.7 cells principally by inhibition of the Akt/mTOR signaling pathway, and they implicate ROS in this regulation.