1, 3-Dichloro-2-Propanol inhibits autophagy via P53/AMPK/mTOR pathway in HepG2 cells. (December 2018)

• Record Type: Journal Article
• Authors: Cheng, Bijun; Lu, Jing; Li, Tianjiao; Meng, Zhuoqun; Liu, Meitong; Sun, Maocheng; Guan, Shuang
• Is Part Of: Food and chemical toxicology. Volume 122(2018)
• Page Start: 143
• Page End: 150
• Publication Date: 2018-12
• Subjects: 1, 3-DCP -- Autophagy -- P53 -- AMPK -- mTOR -- LC3; 1, 3-DCP 1, 3-Dichloro-2-Propanol -- BSA bovine serum albumin -- BCA Bicinchoninic Acid -- DAPI 4′, 6-diamidino-2-phenylindole -- DMEM Dulbecco's Modified Eagle Medium -- ECL Electro-Chemi-Luminescence -- LC3 hypothetical Light chain 3 -- MDC monodansyl cadaverine -- PBS phosphate buffer saline -- PMSF phe-nylmethanesulfonyl fluoride -- PVDF polyvinylidene fluoride -- RIPA radio-Immunoprecipitation Assay -- SDS-PAGE sodium dodecyl sulfate-polyacryl-amide gel electrophoresis -- TEM transmission electron microscope; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2018.10.030
• Languages: English
• ISSNs: 0278-6915

Abstract

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. Graphical abstract: Highlights: 1, 3-DCP exposure inhibited autophagy in a dose dependent manner. A mTOR inhibitor (rapamycin) abolished the ability of 1, 3-DCP to inhibit the induction of autophagy. A reversible AMPK activator(A-769662) abolished the ability of 1, 3-DCP to inhibit the induction of autophagy. A selective P53 activator (Nutlin-3a) abolished the ability of 1, 3-DCP to inhibit the induction of autophagy. P53/AMPK/mTOR signalling pathway played an important role in the regulation of 1, 3-DCP-inhibited autophagy.