1,3-Dichloro-2-Propanol inhibits autophagy via P53/AMPK/mTOR pathway in HepG2 cells

1,3-二氯-2-丙醇通过 P53/AMPK/mTOR 通路抑制 HepG2 细胞自噬

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作者:Bijun Cheng, Jing Lu, Tianjiao Li, Zhuoqun Meng, Meitong Liu, Maocheng Sun, Shuang Guan

Abstract

As a common food processing pollutant, 1,3-Dichloro-2-propanol can be found in foodstuffs, especially in soup spices and instant soups. Mounting researchers have unfolded the relation between 1,3-DCP and various diseases. Autophagy is a process of self-regulation and defects in autophagy have been bound up with multifarious human pathologies and metabolic diseases. Here, we explored the effects of 1,3-DCP on autophagy and traced the molecular mechanism. Our results demonstrated that 1,3-DCP dose-dependently inhibited autophagy. Meanwhile, inhibition of autophagy was accompanied by reduced P53 and p-AMPK/AMPK expressions and stimulated p-mTOR/mTOR expression. Use of a specific mTOR inhibitor (rapamycin), a reversible AMPK activator(A-769662) and a selective P53 activator (Nutlin-3a) abolished the ability of 1,3-DCP to inhibit the induction of autophagy. These evidences suggested that P53/AMPK/mTOR signalling pathway played an important role in the regulation of 1,3-DCP-inhibited autophagy. Together, our results revealed new insights into the toxicity mechanism of 1,3-DCP, supplying theoretical and scientific basis for food safety.

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