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

Copyright © 2018 Elsevier Ltd. All rights reserved..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2018

Erschienen:

2018

Enthalten in:

Zur Gesamtaufnahme - volume:122

Enthalten in:

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association - 122(2018) vom: 15. Dez., Seite 143-150

Sprache:

Englisch

Beteiligte Personen:

Cheng, Bijun [VerfasserIn]
Lu, Jing [VerfasserIn]
Li, Tianjiao [VerfasserIn]
Meng, Zhuoqun [VerfasserIn]
Liu, Meitong [VerfasserIn]
Sun, Maocheng [VerfasserIn]
Guan, Shuang [VerfasserIn]

Links:

Volltext

Themen:

0F4P2VQC07
1,3-DCP
1,3-dichloro-2-propanol
4-hydroxy-3-(4-(2-hydroxyphenyl)phenyl)-6-oxo-7H-thieno(2,3-b)pyridine-5-carbonitrile
53IA0V845C
96-24-2
AMPK
Adenylate Kinase
Alpha-Chlorohydrin
Autophagy
Biphenyl Compounds
EC 2.7.1.1
EC 2.7.11.1
EC 2.7.4.3
Enzyme Activators
Imidazoles
Journal Article
LC3
MTOR
MTOR protein, human
Nutlin 3
P53
P68477CD2C
Piperazines
Pyrones
TOR Serine-Threonine Kinases
TP53 protein, human
Thiophenes
Tumor Suppressor Protein p53

Anmerkungen:

Date Completed 20.02.2019

Date Revised 04.12.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.fct.2018.10.030

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM289517001